Clinical Trials List
Protocol NumberCNTO1275SLE3001
NCT Number(ClinicalTrials.gov Identfier)NCT03517722
2018-04-25 - 2023-07-31
Phase III
Terminated8
ICD-10M32.9
Systemic lupus erythematosus, unspecified
ICD-10M32
Systemic lupus erythematosus (SLE)
ICD-9710.0
Systemic lupus erythematosus
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
Janssen Research & Development, LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 洪偉哲 風濕免疫科
- Po-Hao Huang 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Tzn-Min Lin 風濕免疫科
The Actual Total Number of Participants Enrolled
3 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Hsien-Tzung Liao 風濕免疫科
- 劉德鈴 風濕免疫科
- Wei-Sheng Chen 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
羅淑芬
Co-Principal Investigator
- TianMing Zhan 風濕免疫科
- Yao-Fan Fang 風濕免疫科
- 張哲慈 風濕免疫科
- Chang-Fu Kuo 風濕免疫科
- 陳彥輔 風濕免疫科
- Ping-Han Tsai 風濕免疫科
The Actual Total Number of Participants Enrolled
2 Stop recruiting
Audit
None
Principal Investigator
Co-Principal Investigator
- Wen Chan Tsai 未分科
Audit
None
Co-Principal Investigator
- 郭佑民 風濕免疫科
- KO-JEN LI 風濕免疫科
- CHENG-HAN WU 風濕免疫科
- 呂政勳 風濕免疫科
- CHIEH-YU SHEN 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 歐燦騰 風濕免疫科
- Sung Wan-Yu 風濕免疫科
- 吳正欽 風濕免疫科
- Jeng-Hsien Yen 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Systemic Lupus Erythematosus
Objectives
The primary objective is to evaluate the efficacy of ustekinumab in subjects with active systemic lupus
erythematosus (SLE) who have not adequately responded to one or more standard-of-care treatments.
The secondary objectives are to evaluate the following in subjects with active SLE despite receiving one
or more standard-of-care treatments:
1. Reduction in SLE flares
2. Improvement in global and organ-specific (mucocutaneous, musculoskeletal, etc) measures of SLE
disease activity
3. Glucocorticoid sparing
The additional objectives are to evaluate:
1. Safety and tolerability
2. Pharmacokinetics (PK) and immunogenicity
3. Pharmacodynamic biomarkers and predictive biomarkers to identify subjects most likely to benefit
from treatment with ustekinumab
4. Measures of low disease activity state, remission, and organ damage
5. Effect on health-related quality of life, physical function, and work productivity
Test Drug
Ustekinumab (STELARA)
Active Ingredient
Ustekinumab
Dosage Form
Solution in a single-dose vial
single-dose prefilled syringe
single-dose prefilled syringe
Dosage
130mg
90mg
90mg
Endpoints
The primary endpoint is the proportion of subjects achieving an SLE Responder Index (SRI-4) composite
response at Week 52.
The secondary endpoints are:
1. Time to flare based on the proportion of subjects with a flare occurring at any time after the baseline
visit through Week 52, with flare defined as either 1 or more new British Isles Lupus Assessment
Group (BILAG) A or 2 or more new BILAG B domain scores
2. The proportion of subjects with an SRI-4 composite response at Week 24
3. The proportion of subjects achieving at least a 50% improvement in the number of joints with pain
and signs of inflammation at Week 52 in subjects with at least 4 affected joints at baseline
4. The proportion of subjects receiving glucocorticoids at baseline who achieve reduction in
glucocorticoid dose by Week 40 and sustain that reduction through Week 52
5. The proportion of subjects achieving at least a 50% improvement in the Cutaneous Lupus
Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 52 in subjects with a CLASI Activity Score of 4 or greater at baseline.
6. The proportion of subjects receiving glucocorticoids at baseline who achieve reduction in glucocorticoid dose by Week 40, sustain that reduction through Week 52, and achieve an SRI-4 composite response at Week 52
response at Week 52.
The secondary endpoints are:
1. Time to flare based on the proportion of subjects with a flare occurring at any time after the baseline
visit through Week 52, with flare defined as either 1 or more new British Isles Lupus Assessment
Group (BILAG) A or 2 or more new BILAG B domain scores
2. The proportion of subjects with an SRI-4 composite response at Week 24
3. The proportion of subjects achieving at least a 50% improvement in the number of joints with pain
and signs of inflammation at Week 52 in subjects with at least 4 affected joints at baseline
4. The proportion of subjects receiving glucocorticoids at baseline who achieve reduction in
glucocorticoid dose by Week 40 and sustain that reduction through Week 52
5. The proportion of subjects achieving at least a 50% improvement in the Cutaneous Lupus
Erythematosus Disease Area and Severity Index (CLASI) Activity Score at Week 52 in subjects with a CLASI Activity Score of 4 or greater at baseline.
6. The proportion of subjects receiving glucocorticoids at baseline who achieve reduction in glucocorticoid dose by Week 40, sustain that reduction through Week 52, and achieve an SRI-4 composite response at Week 52
Inclution Criteria
Inclusion Criteria
Each potential subject must satisfy all the following criteria to be enrolled in the study:
1. Be male or female (according to their reproductive organs and functions assigned by
chromosomal complement)
2. Subjects who are considered to be adults legally (per local requirements) must sign an
informed consent form (ICF) indicating that he or she understands the purpose of, and
procedures required for, the study and is willing to participate in the study. Subjects
who are not considered to be adults legally (per local requirements) must have
parent(s) (preferably both if available or as per local requirements) (or their legally
acceptable representative) sign an ICF indicating that he or she understands the purpose
of, and procedures required for, the study and is willing to allow the child to participate
in the study. Assent is also required of children capable of understanding the nature of
the study as described in Section 16.2.3, Informed Consent.
3. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
4. Be between 16 (unless restricted by local requirements) and 75 years of age, inclusive.
5. Had a diagnosis of SLE made or confirmed by a physician (such as a rheumatologist,
nephrologist, internal medicine specialist, or dermatologist) experienced in the treatment of SLE.
6. Had a documented medical history that subject met the SLICC classification criteria for SLE
41 (meeting at least 4 SLICC criteria in total including at least 1 immunologic criteria; Attachment 1) at least 3 months prior to first dose of study agent
7. Have at least 1 well-documented (subject file, referring physician letter, or laboratory
result) unequivocally positive test in medical history for at least 1 of the following
autoantibodies: ANA, anti-dsDNA, and/or anti-Smith
8. Have at least 1 unequivocally positive autoantibody test including ANA (≥1:80 titer by
Central Lab test) and/or anti-dsDNA antibodies and/or anti-Smith antibodies detected during screening.
9. Have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.
10. Have a CLASI activity score of at least 4 (excluding diffuse non-inflammatory
alopecia) or at least 4 joints with pain and signs of inflammation (active joints) at
screening or at Week 0, or both.
11. Demonstrate active disease based on SLEDAI-2K score ≥6 observed during screening.
Must also have SLEDAI-2K ≥4 for clinical features (ie, SLEDAI-2K score excluding
headache, and laboratory abnormalities) present at Week 0 prior to randomization.
12. Must be receiving one or more of the following protocol-permitted, systemic standardof-care treatments:
a) Oral glucocorticoids (average daily dose ≤20 mg of prednisone or equivalent)
for ≥6 weeks and at a stable dose ≥4 weeks prior to first dose of study agent
o If currently not using oral glucocorticoids, must not have received them
for ≥6 weeks prior to the first dose of study agent.
b) Antimalarials (≤250 mg/day chloroquine, ≤400 mg/day hydroxychloroquine,
and/or ≤100 mg/day quinacrine) for ≥12 weeks and at a stable dose for ≥6
weeks prior to first dose of study agent
c) If using one or more of the following immunomodulatory drugs, must be
receiving for ≥12 weeks and be on a stable dose for ≥6 weeks prior to first dose of study agent:
o MMF ≤2 g/day
o MPA ≤1.5 g/day
o AZA /6-MP ≤2 mg/kg/day; up to 100 mg/day for subjects weighing ≤50 kg
o Oral MTX ≤25 mg/Week or SC or intramuscular (IM) MTX
≤20 mg/Week with concomitant folic acid or folinic acid
If the subject is using concomitantly 2 or more of the immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX), the suitability of the
subject to participate in the study must be discussed with the medical
monitor and/or sponsor before the subject is randomized.
13. Regular or as needed treatment with the following agents with no changes in dose or
frequency is permitted as follows:
a) Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor
blockers (ARBs) for ≥2 weeks prior to first dose of study agent
b) Nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics for ≥2
weeks prior to first dose of study agent
c) Permitted topical medications for cutaneous disease (Section 8.1.6) for
≥4 weeks prior to first dose of study agent
o Must not be using any prohibited topical medications (such as tacrolimus,
pimecrolimus, dapsone, thalidomide), with the exception of cyclosporine
A for ophthalmic use
14. Contraceptive use by men or women should be consistent with local regulations
regarding the use of contraceptive methods for subjects participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly.
Use should be consistent with local regulations regarding the use of contraceptive
methods for subjects in clinical studies.
Before randomization, a woman must be either:
a. Not of childbearing potential, defined as:
1) Premenarchal: A premenarchal state is one in which menarche has not yet occurred.
2) Postmenopausal: A postmenopausal state is defined as no menses for 12
months without an alternative medical cause. A high follicle-stimulating
hormone (FSH) level (>40 IU/L or mIU/mL) in the postmenopausal range may
be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy; however, in the absence of 12
months of amenorrhea, a single FSH measurement is insufficient.
3) Permanently sterile: Permanent sterilization methods include hysterectomy,
bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and
bilateral oophorectomy.
or
b. Of childbearing potential:
1) Practicing a highly effective method of contraception (failure rate of <1% per
year when used consistently and correctly) consistent with local regulations
regarding the use of birth control methods for subjects participating in clinical
studies: eg, hormone contraception associated with inhibition of ovulation;
intrauterine device (IUD); intrauterine hormone-releasing system (IUS);
bilateral tubal occlusion; vasectomized partner; sexual abstinence (sexual
abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk
associated with the study agent. The reliability of sexual abstinence needs to
be evaluated in relation to the duration of the study and the preferred and
usual lifestyle of the subject.
2) Agrees to remain on a highly effective method of contraception throughout
the study and for at least 16 weeks after the last dose of study agent.
Note: If childbearing potential changes after start of the study (eg, a woman who is not
heterosexually active becomes active, or a premenarchal woman experiences
menarche) a woman must begin a highly effective method of birth control, as described above.
15. A woman of childbearing potential must have a negative urine pregnancy tests
(-human chorionic gonadotropin [-hCG]) obtained during screening and at Week 0
before the first dose of study agent.
16. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for 4 months after receiving the last dose of study
agent.
17. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. A man who
is sexually active with a woman who is pregnant must use a condom and all men must
not donate sperm during the study and for 20 weeks after receiving the last dose of study agent.
18. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. An exception is made
for subjects who have a history of latent TB and are currently receiving
treatment for latent TB, will initiate treatment for latent TB prior to first
administration of study agent, or have documentation of having completed
appropriate treatment for latent TB within 3 years prior to the first
administration of study agent. It is the responsibility of the Investigator to
verify the adequacy of previous anti-tuberculous treatment and provide
appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had no recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to undergo
additional evaluation and, if warranted, receive appropriate treatment for latent
TB prior to the first administration of study agent.
d. Within 6 weeks prior to the first administration of study agent, has a negative
QuantiFERON®-TB Gold test result (Attachment 2), or have a newly identified
positive QuantiFERON®
-TB Gold test result in which active TB has been ruled
out and for which appropriate treatment for latent TB has been initiated prior to
the first administration of study agent. Within 6 weeks prior to the first
administration of study agent, a negative tuberculin skin test, or a newly
identified positive tuberculin skin test in which active TB has been ruled out
and for which appropriate treatment for latent TB has been initiated prior to the
first administration of study agent, is additionally required if the QuantiFERON®
-TB Gold test is not approved/registered in that country or the
tuberculin skin test is mandated by local health authorities.
i. A subject whose first QuantiFERON®
-TB Gold test result is
indeterminate should have the test repeated. In the event that the second
QuantiFERON®
-TB Gold test result is also indeterminate, the subject
may be enrolled without treatment for latent TB, if active TB is ruled
out, their chest radiograph shows no abnormality suggestive of TB
(active or old, inactive TB), and the subject has no additional risk
factors for TB as determined by the Investigator. This determination
must be promptly reported to the Sponsor’s medical monitor and
recorded in the subject's source documents and initialed by the Investigator.
ii. The QuantiFERON®
-TB Gold test and the tuberculin skin test are not
required at screening for subjects with a history of latent TB and
ongoing treatment for latent TB or documentation of having completed
adequate treatment as described above; Subjects with documentation of
having completed adequate treatment as described above are not
required to initiate additional treatment for latent TB.
e. Have a chest radiograph, both posterior-anterior and lateral views (consistent
with local regulations), taken within 3 months prior to the first administration of
study agent and read by a qualified radiologist or pulmonologist, with no
evidence of current, active TB or old, inactive TB.
19. Subjects must have laboratory test results within the following parameters at screening:
Hemoglobin, Lymphocytes, Neutrophils, Platelets, Serum creatinine
Each potential subject must satisfy all the following criteria to be enrolled in the study:
1. Be male or female (according to their reproductive organs and functions assigned by
chromosomal complement)
2. Subjects who are considered to be adults legally (per local requirements) must sign an
informed consent form (ICF) indicating that he or she understands the purpose of, and
procedures required for, the study and is willing to participate in the study. Subjects
who are not considered to be adults legally (per local requirements) must have
parent(s) (preferably both if available or as per local requirements) (or their legally
acceptable representative) sign an ICF indicating that he or she understands the purpose
of, and procedures required for, the study and is willing to allow the child to participate
in the study. Assent is also required of children capable of understanding the nature of
the study as described in Section 16.2.3, Informed Consent.
3. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
4. Be between 16 (unless restricted by local requirements) and 75 years of age, inclusive.
5. Had a diagnosis of SLE made or confirmed by a physician (such as a rheumatologist,
nephrologist, internal medicine specialist, or dermatologist) experienced in the treatment of SLE.
6. Had a documented medical history that subject met the SLICC classification criteria for SLE
41 (meeting at least 4 SLICC criteria in total including at least 1 immunologic criteria; Attachment 1) at least 3 months prior to first dose of study agent
7. Have at least 1 well-documented (subject file, referring physician letter, or laboratory
result) unequivocally positive test in medical history for at least 1 of the following
autoantibodies: ANA, anti-dsDNA, and/or anti-Smith
8. Have at least 1 unequivocally positive autoantibody test including ANA (≥1:80 titer by
Central Lab test) and/or anti-dsDNA antibodies and/or anti-Smith antibodies detected during screening.
9. Have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.
10. Have a CLASI activity score of at least 4 (excluding diffuse non-inflammatory
alopecia) or at least 4 joints with pain and signs of inflammation (active joints) at
screening or at Week 0, or both.
11. Demonstrate active disease based on SLEDAI-2K score ≥6 observed during screening.
Must also have SLEDAI-2K ≥4 for clinical features (ie, SLEDAI-2K score excluding
headache, and laboratory abnormalities) present at Week 0 prior to randomization.
12. Must be receiving one or more of the following protocol-permitted, systemic standardof-care treatments:
a) Oral glucocorticoids (average daily dose ≤20 mg of prednisone or equivalent)
for ≥6 weeks and at a stable dose ≥4 weeks prior to first dose of study agent
o If currently not using oral glucocorticoids, must not have received them
for ≥6 weeks prior to the first dose of study agent.
b) Antimalarials (≤250 mg/day chloroquine, ≤400 mg/day hydroxychloroquine,
and/or ≤100 mg/day quinacrine) for ≥12 weeks and at a stable dose for ≥6
weeks prior to first dose of study agent
c) If using one or more of the following immunomodulatory drugs, must be
receiving for ≥12 weeks and be on a stable dose for ≥6 weeks prior to first dose of study agent:
o MMF ≤2 g/day
o MPA ≤1.5 g/day
o AZA /6-MP ≤2 mg/kg/day; up to 100 mg/day for subjects weighing ≤50 kg
o Oral MTX ≤25 mg/Week or SC or intramuscular (IM) MTX
≤20 mg/Week with concomitant folic acid or folinic acid
If the subject is using concomitantly 2 or more of the immunomodulatory drugs listed above (MMF, MPA, AZA, 6-MP, MTX), the suitability of the
subject to participate in the study must be discussed with the medical
monitor and/or sponsor before the subject is randomized.
13. Regular or as needed treatment with the following agents with no changes in dose or
frequency is permitted as follows:
a) Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor
blockers (ARBs) for ≥2 weeks prior to first dose of study agent
b) Nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics for ≥2
weeks prior to first dose of study agent
c) Permitted topical medications for cutaneous disease (Section 8.1.6) for
≥4 weeks prior to first dose of study agent
o Must not be using any prohibited topical medications (such as tacrolimus,
pimecrolimus, dapsone, thalidomide), with the exception of cyclosporine
A for ophthalmic use
14. Contraceptive use by men or women should be consistent with local regulations
regarding the use of contraceptive methods for subjects participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly.
Use should be consistent with local regulations regarding the use of contraceptive
methods for subjects in clinical studies.
Before randomization, a woman must be either:
a. Not of childbearing potential, defined as:
1) Premenarchal: A premenarchal state is one in which menarche has not yet occurred.
2) Postmenopausal: A postmenopausal state is defined as no menses for 12
months without an alternative medical cause. A high follicle-stimulating
hormone (FSH) level (>40 IU/L or mIU/mL) in the postmenopausal range may
be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy; however, in the absence of 12
months of amenorrhea, a single FSH measurement is insufficient.
3) Permanently sterile: Permanent sterilization methods include hysterectomy,
bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and
bilateral oophorectomy.
or
b. Of childbearing potential:
1) Practicing a highly effective method of contraception (failure rate of <1% per
year when used consistently and correctly) consistent with local regulations
regarding the use of birth control methods for subjects participating in clinical
studies: eg, hormone contraception associated with inhibition of ovulation;
intrauterine device (IUD); intrauterine hormone-releasing system (IUS);
bilateral tubal occlusion; vasectomized partner; sexual abstinence (sexual
abstinence is considered a highly effective method only if defined as
refraining from heterosexual intercourse during the entire period of risk
associated with the study agent. The reliability of sexual abstinence needs to
be evaluated in relation to the duration of the study and the preferred and
usual lifestyle of the subject.
2) Agrees to remain on a highly effective method of contraception throughout
the study and for at least 16 weeks after the last dose of study agent.
Note: If childbearing potential changes after start of the study (eg, a woman who is not
heterosexually active becomes active, or a premenarchal woman experiences
menarche) a woman must begin a highly effective method of birth control, as described above.
15. A woman of childbearing potential must have a negative urine pregnancy tests
(-human chorionic gonadotropin [-hCG]) obtained during screening and at Week 0
before the first dose of study agent.
16. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for 4 months after receiving the last dose of study
agent.
17. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control eg, either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. A man who
is sexually active with a woman who is pregnant must use a condom and all men must
not donate sperm during the study and for 20 weeks after receiving the last dose of study agent.
18. Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. An exception is made
for subjects who have a history of latent TB and are currently receiving
treatment for latent TB, will initiate treatment for latent TB prior to first
administration of study agent, or have documentation of having completed
appropriate treatment for latent TB within 3 years prior to the first
administration of study agent. It is the responsibility of the Investigator to
verify the adequacy of previous anti-tuberculous treatment and provide
appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had no recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to undergo
additional evaluation and, if warranted, receive appropriate treatment for latent
TB prior to the first administration of study agent.
d. Within 6 weeks prior to the first administration of study agent, has a negative
QuantiFERON®-TB Gold test result (Attachment 2), or have a newly identified
positive QuantiFERON®
-TB Gold test result in which active TB has been ruled
out and for which appropriate treatment for latent TB has been initiated prior to
the first administration of study agent. Within 6 weeks prior to the first
administration of study agent, a negative tuberculin skin test, or a newly
identified positive tuberculin skin test in which active TB has been ruled out
and for which appropriate treatment for latent TB has been initiated prior to the
first administration of study agent, is additionally required if the QuantiFERON®
-TB Gold test is not approved/registered in that country or the
tuberculin skin test is mandated by local health authorities.
i. A subject whose first QuantiFERON®
-TB Gold test result is
indeterminate should have the test repeated. In the event that the second
QuantiFERON®
-TB Gold test result is also indeterminate, the subject
may be enrolled without treatment for latent TB, if active TB is ruled
out, their chest radiograph shows no abnormality suggestive of TB
(active or old, inactive TB), and the subject has no additional risk
factors for TB as determined by the Investigator. This determination
must be promptly reported to the Sponsor’s medical monitor and
recorded in the subject's source documents and initialed by the Investigator.
ii. The QuantiFERON®
-TB Gold test and the tuberculin skin test are not
required at screening for subjects with a history of latent TB and
ongoing treatment for latent TB or documentation of having completed
adequate treatment as described above; Subjects with documentation of
having completed adequate treatment as described above are not
required to initiate additional treatment for latent TB.
e. Have a chest radiograph, both posterior-anterior and lateral views (consistent
with local regulations), taken within 3 months prior to the first administration of
study agent and read by a qualified radiologist or pulmonologist, with no
evidence of current, active TB or old, inactive TB.
19. Subjects must have laboratory test results within the following parameters at screening:
Hemoglobin, Lymphocytes, Neutrophils, Platelets, Serum creatinine
Exclusion Criteria
1. Has any unstable or progressive manifestation of SLE (lupus cerebritis, optic neuritis,
transverse myelitis, psychosis, uncontrolled seizures, systemic vasculitis, end-stage
renal disease, severe or rapidly progressive Class III or IV glomerulonephritis,
isolated Class V lupus nephritis [ie, without coexistent Class I, II, III, or IV nephritis],
Class VI lupus nephritis, pulmonary hemorrhage, myocarditis) that is likely to warrant
escalation in therapy beyond permitted background medications.
2. Has other inflammatory diseases that might confound the evaluations of efficacy,
including but not limited to rheumatoid arthritis (RA), PsA, RA/lupus overlap,
psoriasis, Crohn’s disease, or active Lyme disease.
3. Is pregnant, nursing, or planning a pregnancy or planning to father a child while
enrolled in the study or within 4 months after receiving the last administration of study agent.
4. Is an employee of the Investigator or study site (ie, personnel to whom the
Investigator has delegated a role or responsibility for conducting the study), with
direct involvement in the proposed study or other studies under the direction of that
Investigator or study site, as well as family members of the employees or the Investigator.
5. Lives in an institution on court or authority order, unless permitted by local regulations.
Concomitant or previous medical therapies received:
6. Has received systemic immunomodulatory agents (eg, leflunomide, tacrolimus,
sirolimus, mizoribine) other than those described in inclusion criteria within 3 months
prior to the first dose of study agent (Section 8.1.6). Glucocorticoids are not included
in this criterion; see Section 8.1.2 regarding glucocorticoid use.
7. Has used oral cyclophosphamide within 90 days or IV cyclophosphamide within
180 days of starting screening.
8. Exclusions for treatment with B-cell targeted therapies (eg, belimumab, rituximab,
epratuzumab) are as follows:
a. Treatment with a single B-cell targeted therapy within 3 months prior to first
dose of study agent.
b. Treatment with >1 previous B-cell targeting therapy within 6 months prior to
first dose of study agent.
c. Treatment with B-cell depleting therapy (eg, rituximab, epratuzumab) within 12
months prior to first dose of study agent, or have evidence of continued B-cell
depletion following such therapy
9. Has ever received ustekinumab.
10. Has received prior immunomodulatory biologic therapy not described in Section 8.1.7
such as tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra,
brodalumab, secukinumab, ixekizumab, or agents whose mechanism of action targets
tumor necrosis factor alpha (TNFα), IL-1, IL-2, IL-6, IL-17, or IFN pathways, less
than 5 half-lives or 3 months, whichever is longer, prior to first dose of the study agent.
11. Has received adrenocorticotropic hormone (ACTH) administered by injection within
1 month prior to the first administration of study agent.
12. Has received topical cream/ointment preparations of cyclosporine A (except for
ophthalmic use), or other topical immunomodulatory agents (such as tacrolimus,
pimecrolimus) within 4 weeks prior to the first administration of study agent.
13. Has received an investigational drug that is not previously defined in other exclusion
criteria (including investigational vaccines or other medications specified in
Section 4.2) within 5 half-lives or 3 months, whichever is longer, or used an invasive
investigational medical device within 3 months before the planned first dose of study
agent, or is currently enrolled in an interventional study.
14. Is currently receiving venom immunotherapy (honeybee, wasp, yellow jacket, hornet,
or fire ant).
15. Subjects likely to require multiple courses of systemic steroids (eg, uncontrolled
asthma, uncontrolled chronic obstructive pulmonary disease, etc) for reasons other
than SLE should be excluded from study participation.
16. Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional
administration of glucocorticoids within 6 weeks prior to the first administration of
study agent.
17. Use of complementary therapies, including traditional/Chinese medicines, herbs,
ointments, or procedures (eg, acupuncture), that have the potential to activate (eg,
echinacea) or inhibit (eg, Tripterygium wilfordii Hook F) the immune system is
prohibited within 6 weeks of the first administration of study agent. In addition, use of
complementary therapies, including traditional/Chinese medicines and herbs, that
have the potential to interact with antithrombotic agents (eg, St. John’s Wort) is
prohibited within 6 weeks of the first administration of study agent in those taking
antithrombotic agents. Any questions or concerns with the use of these therapies
should be discussed with the study sponsor and/or medical monitor.
18. Has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
19. Has received a live virus or live bacterial vaccination within 16 weeks prior to the first
administration of study agent.
20. Has a history of active granulomatous infection, including histoplasmosis, or
coccidioidomycosis. Refer to Section 4.1 for information regarding eligibility with a
history of latent TB.
21. Has a chest radiograph within 3 months prior to the first administration of study agent
that shows an abnormality suggestive of a malignancy or current active infection,
including TB. Radiographic findings such as pulmonary nodules should be evaluated
by an experienced radiologist and/or pulmonologist to determine whether the
presentation is suggestive of infection or active malignancy and final assessment
documented by the Investigator prior to randomization.
22. Has had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystosis, aspergillosis).
23. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not
limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), chronic
infectious sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis), an
open, draining, or infected skin wound or ulcer.
24. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests
positive for HIV at screening.
25. Has a hepatitis B infection. Subjects must undergo screening for hepatitis B virus
(HBV; Attachment 5). At a minimum, this includes testing for HBsAg (HBV surface
antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core antibody total).
26. Is seropositive for antibodies to hepatitis C virus (HCV), unless has 2 negative HCV
RNA test results 6 months apart prior to screening and has a third negative HCV RNA
test result at screening.
27. Has experienced a recent single dermatomal herpes zoster eruption within the past
4 months. Has ever had multi-dermatomal herpes zoster (defined as appearance of
lesion outside the primary or adjacent dermatome) or CNS zoster infection.
28. Within 2 months prior to first administration of study agent, has had a serious
infection (eg, pneumonia, sepsis, or pyelonephritis), or has been hospitalized for an
infection, or has been treated with IV antibiotics for an infection. Less serious
infections (eg, acute upper respiratory tract infection, simple urinary tract infection)
need not be considered exclusionary at the discretion of the Investigator.
Concurrent medical conditions or past medical history and procedures:
29. Has a history or suspected occurrence of drug-induced lupus.
30. Has inherited complement deficiency or combined variable immunodeficiency.
31. Has urinary protein level of >4 g/day or protein/creatinine ratio estimating >4g/day
equivalent proteinuria.
32. Has a history of catastrophic antiphospholipid syndrome (APS). Subjects with a
history of non-catastrophic APS must be adequately controlled with anticoagulation
and/or anti-platelet therapy in accordance with local guidelines. The suitability of the
subject to participate in the study must be discussed with the medical monitor and/or
sponsor before the subject is randomized
33. Has a known hypersensitivity to human immunoglobulin (Ig) proteins (eg, IV Ig).
34. Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
(see Section 14.1 and the ustekinumab Investigator’s Brochure).
35. Any major illness/condition or evidence of an unstable clinical condition (eg, renal,
hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic,
psychiatric), disease of any organ system, or active acute or chronic
infection/infectious illness that, in the Investigator’s judgment, will substantially
increase the risk to the participant if he or she participates in the study.
36. Has had major surgery, (eg, requiring general anesthesia) within 1 month before
screening, or will not have fully recovered from surgery, or has major surgery (eg,
requiring general anesthesia) planned during the time the subject is expected to
participate in the study or within 1 month after the last dose of study agent
administration.
Note: Subjects with planned minor surgical procedures to be conducted under local
anesthesia may participate after discussion with the medical monitor and/or sponsor.
37. Has a transplanted organ (except for a corneal transplant performed >3 months prior
to first administration of study agent).
38. Uses semipermanently attached wigs that would interfere with scoring of cutaneous disease.
39. Has or has had a substance abuse (drug or alcohol) problem within the previous 3 years.
40. Is unwilling or unable to undergo multiple venipunctures because of poor tolerability
or lack of easy venous access.
Malignancy or increased potential for malignancy:
41. Presence or history of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin that has been treated with no evidence
of recurrence for at least 3 months before the first study agent administration and
carcinoma in situ of the cervix that has been documented to be surgically cured).
42. Has a known history of lymphoproliferative disease, including lymphoma, or signs
and symptoms suggestive of possible lymphoproliferative disease, such as
lymphadenopathy of unusual size or location, clinically significant splenomegaly, or
history of monoclonal gammopathy of undetermined significance.
Additional concomitant or previous medical therapies received:
43. Use of IV gamma globulin, apheresis therapy (including but not limited to
plasmapheresis, photopheresis, leukocytapheresis), or immunoadsorption is prohibited
within 6 months prior to the first administration of study agent and within 4 months
after receiving the last administration of study agent.
44. Has ever received stem cell transplantation (including hematopoietic stem cell
transplantation and mesenchymal stem cell transplantation)
transverse myelitis, psychosis, uncontrolled seizures, systemic vasculitis, end-stage
renal disease, severe or rapidly progressive Class III or IV glomerulonephritis,
isolated Class V lupus nephritis [ie, without coexistent Class I, II, III, or IV nephritis],
Class VI lupus nephritis, pulmonary hemorrhage, myocarditis) that is likely to warrant
escalation in therapy beyond permitted background medications.
2. Has other inflammatory diseases that might confound the evaluations of efficacy,
including but not limited to rheumatoid arthritis (RA), PsA, RA/lupus overlap,
psoriasis, Crohn’s disease, or active Lyme disease.
3. Is pregnant, nursing, or planning a pregnancy or planning to father a child while
enrolled in the study or within 4 months after receiving the last administration of study agent.
4. Is an employee of the Investigator or study site (ie, personnel to whom the
Investigator has delegated a role or responsibility for conducting the study), with
direct involvement in the proposed study or other studies under the direction of that
Investigator or study site, as well as family members of the employees or the Investigator.
5. Lives in an institution on court or authority order, unless permitted by local regulations.
Concomitant or previous medical therapies received:
6. Has received systemic immunomodulatory agents (eg, leflunomide, tacrolimus,
sirolimus, mizoribine) other than those described in inclusion criteria within 3 months
prior to the first dose of study agent (Section 8.1.6). Glucocorticoids are not included
in this criterion; see Section 8.1.2 regarding glucocorticoid use.
7. Has used oral cyclophosphamide within 90 days or IV cyclophosphamide within
180 days of starting screening.
8. Exclusions for treatment with B-cell targeted therapies (eg, belimumab, rituximab,
epratuzumab) are as follows:
a. Treatment with a single B-cell targeted therapy within 3 months prior to first
dose of study agent.
b. Treatment with >1 previous B-cell targeting therapy within 6 months prior to
first dose of study agent.
c. Treatment with B-cell depleting therapy (eg, rituximab, epratuzumab) within 12
months prior to first dose of study agent, or have evidence of continued B-cell
depletion following such therapy
9. Has ever received ustekinumab.
10. Has received prior immunomodulatory biologic therapy not described in Section 8.1.7
such as tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra,
brodalumab, secukinumab, ixekizumab, or agents whose mechanism of action targets
tumor necrosis factor alpha (TNFα), IL-1, IL-2, IL-6, IL-17, or IFN pathways, less
than 5 half-lives or 3 months, whichever is longer, prior to first dose of the study agent.
11. Has received adrenocorticotropic hormone (ACTH) administered by injection within
1 month prior to the first administration of study agent.
12. Has received topical cream/ointment preparations of cyclosporine A (except for
ophthalmic use), or other topical immunomodulatory agents (such as tacrolimus,
pimecrolimus) within 4 weeks prior to the first administration of study agent.
13. Has received an investigational drug that is not previously defined in other exclusion
criteria (including investigational vaccines or other medications specified in
Section 4.2) within 5 half-lives or 3 months, whichever is longer, or used an invasive
investigational medical device within 3 months before the planned first dose of study
agent, or is currently enrolled in an interventional study.
14. Is currently receiving venom immunotherapy (honeybee, wasp, yellow jacket, hornet,
or fire ant).
15. Subjects likely to require multiple courses of systemic steroids (eg, uncontrolled
asthma, uncontrolled chronic obstructive pulmonary disease, etc) for reasons other
than SLE should be excluded from study participation.
16. Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional
administration of glucocorticoids within 6 weeks prior to the first administration of
study agent.
17. Use of complementary therapies, including traditional/Chinese medicines, herbs,
ointments, or procedures (eg, acupuncture), that have the potential to activate (eg,
echinacea) or inhibit (eg, Tripterygium wilfordii Hook F) the immune system is
prohibited within 6 weeks of the first administration of study agent. In addition, use of
complementary therapies, including traditional/Chinese medicines and herbs, that
have the potential to interact with antithrombotic agents (eg, St. John’s Wort) is
prohibited within 6 weeks of the first administration of study agent in those taking
antithrombotic agents. Any questions or concerns with the use of these therapies
should be discussed with the study sponsor and/or medical monitor.
18. Has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
19. Has received a live virus or live bacterial vaccination within 16 weeks prior to the first
administration of study agent.
20. Has a history of active granulomatous infection, including histoplasmosis, or
coccidioidomycosis. Refer to Section 4.1 for information regarding eligibility with a
history of latent TB.
21. Has a chest radiograph within 3 months prior to the first administration of study agent
that shows an abnormality suggestive of a malignancy or current active infection,
including TB. Radiographic findings such as pulmonary nodules should be evaluated
by an experienced radiologist and/or pulmonologist to determine whether the
presentation is suggestive of infection or active malignancy and final assessment
documented by the Investigator prior to randomization.
22. Has had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystosis, aspergillosis).
23. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not
limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), chronic
infectious sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis), an
open, draining, or infected skin wound or ulcer.
24. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests
positive for HIV at screening.
25. Has a hepatitis B infection. Subjects must undergo screening for hepatitis B virus
(HBV; Attachment 5). At a minimum, this includes testing for HBsAg (HBV surface
antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core antibody total).
26. Is seropositive for antibodies to hepatitis C virus (HCV), unless has 2 negative HCV
RNA test results 6 months apart prior to screening and has a third negative HCV RNA
test result at screening.
27. Has experienced a recent single dermatomal herpes zoster eruption within the past
4 months. Has ever had multi-dermatomal herpes zoster (defined as appearance of
lesion outside the primary or adjacent dermatome) or CNS zoster infection.
28. Within 2 months prior to first administration of study agent, has had a serious
infection (eg, pneumonia, sepsis, or pyelonephritis), or has been hospitalized for an
infection, or has been treated with IV antibiotics for an infection. Less serious
infections (eg, acute upper respiratory tract infection, simple urinary tract infection)
need not be considered exclusionary at the discretion of the Investigator.
Concurrent medical conditions or past medical history and procedures:
29. Has a history or suspected occurrence of drug-induced lupus.
30. Has inherited complement deficiency or combined variable immunodeficiency.
31. Has urinary protein level of >4 g/day or protein/creatinine ratio estimating >4g/day
equivalent proteinuria.
32. Has a history of catastrophic antiphospholipid syndrome (APS). Subjects with a
history of non-catastrophic APS must be adequately controlled with anticoagulation
and/or anti-platelet therapy in accordance with local guidelines. The suitability of the
subject to participate in the study must be discussed with the medical monitor and/or
sponsor before the subject is randomized
33. Has a known hypersensitivity to human immunoglobulin (Ig) proteins (eg, IV Ig).
34. Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
(see Section 14.1 and the ustekinumab Investigator’s Brochure).
35. Any major illness/condition or evidence of an unstable clinical condition (eg, renal,
hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic,
psychiatric), disease of any organ system, or active acute or chronic
infection/infectious illness that, in the Investigator’s judgment, will substantially
increase the risk to the participant if he or she participates in the study.
36. Has had major surgery, (eg, requiring general anesthesia) within 1 month before
screening, or will not have fully recovered from surgery, or has major surgery (eg,
requiring general anesthesia) planned during the time the subject is expected to
participate in the study or within 1 month after the last dose of study agent
administration.
Note: Subjects with planned minor surgical procedures to be conducted under local
anesthesia may participate after discussion with the medical monitor and/or sponsor.
37. Has a transplanted organ (except for a corneal transplant performed >3 months prior
to first administration of study agent).
38. Uses semipermanently attached wigs that would interfere with scoring of cutaneous disease.
39. Has or has had a substance abuse (drug or alcohol) problem within the previous 3 years.
40. Is unwilling or unable to undergo multiple venipunctures because of poor tolerability
or lack of easy venous access.
Malignancy or increased potential for malignancy:
41. Presence or history of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin that has been treated with no evidence
of recurrence for at least 3 months before the first study agent administration and
carcinoma in situ of the cervix that has been documented to be surgically cured).
42. Has a known history of lymphoproliferative disease, including lymphoma, or signs
and symptoms suggestive of possible lymphoproliferative disease, such as
lymphadenopathy of unusual size or location, clinically significant splenomegaly, or
history of monoclonal gammopathy of undetermined significance.
Additional concomitant or previous medical therapies received:
43. Use of IV gamma globulin, apheresis therapy (including but not limited to
plasmapheresis, photopheresis, leukocytapheresis), or immunoadsorption is prohibited
within 6 months prior to the first administration of study agent and within 4 months
after receiving the last administration of study agent.
44. Has ever received stem cell transplantation (including hematopoietic stem cell
transplantation and mesenchymal stem cell transplantation)
The Estimated Number of Participants
-
Taiwan
60 participants
-
Global
831 participants
