Clinical Trials List
Protocol NumberIM011021
NCT Number(ClinicalTrials.gov Identfier)NCT03252587
2018-06-29 - 2022-06-30
Phase II
Recruiting8
ICD-10M32
Systemic lupus erythematosus (SLE)
ICD-9710.0
Systemic lupus erythematosus
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects With Systemic Lupus Erythematosus
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Bristol-Myers Squibb
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ping-Han Tsai 無
- TianMing Zhan 無
- 張哲慈 無
- Shue-Fen Lo 無
- Yao-Fan Fang 無
- 陳彥輔 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 郭佑民 Division of Rheumatology
- SONG-CHOU HSIEH Division of Rheumatology
- 呂政勳 無
- CHIEH-YU SHEN Division of Rheumatology
- CHENG-HAN WU Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
4 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Systemic Lupus Erythematosus
Objectives
Primary Objective: To assess the effect of BMS-986165 on BICLA response at Week 32 in subjects
with SLE
Secondary Objective: To assess the effect of BMS-986165 on measures of global and organ-specific
SLE clinical response
Test Drug
BMS-986165
Active Ingredient
BMS-986165
Dosage Form
capsule
Dosage
3 mg
Endpoints
Primary Endpoint: Proportion of subjects who achieve BICLA response at Week 32 after treatment
with BMS-986165 or placebo administered on stable background therapy
Secondary Endpoints:
o Proportion of subjects who meet response criteria for SLE Responder Index
(SRI)(4) at Week 32
o Proportion of subjects with a Cutaneous Lupus Erythematosus Disease Area and
Severity Index (CLASI) activity score ≥ 10 at baseline who achieve a CLASI
response, defined as a decrease of ≥ 50% from baseline CLASI activity score at
Week 32 (Section 9.1)
o Change from baseline in the 40-joint count for tender, swollen, and
tender + swollen joints at Week 32
with BMS-986165 or placebo administered on stable background therapy
Secondary Endpoints:
o Proportion of subjects who meet response criteria for SLE Responder Index
(SRI)(4) at Week 32
o Proportion of subjects with a Cutaneous Lupus Erythematosus Disease Area and
Severity Index (CLASI) activity score ≥ 10 at baseline who achieve a CLASI
response, defined as a decrease of ≥ 50% from baseline CLASI activity score at
Week 32 (Section 9.1)
o Change from baseline in the 40-joint count for tender, swollen, and
tender + swollen joints at Week 32
Inclution Criteria
Inclusion Criteria
1) Signed Written Informed Consent
a) Willing to participate in the study and sign the informed consent form (ICF).
b) Willing and able to complete all study-specific procedures and visits.
2) SLE Disease Characteristics
a) Diagnosed ≥ 24 weeks before the screening visit
b) Meets the SLICC classification criteria for SLE.
c) One of the following: elevated antinuclear antibodies (ANA) ≥ 1:80 or positive anti-dsDNA (positive includes indeterminate results) or positive anti-Smith (anti-Sm) as determined by the central laboratory.
d) Total SLEDAI-2K score ≥ 6 points and clinical SLEDAI-2K score ≥ 4 points with joint involvement and/or rash
o Lupus headache, alopecia, organic brain syndrome, and mucosal ulcers cannot count toward the points required for screening at entry.
o Clinical SLEDAI-2K excludes laboratory abnormalities such as hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA,
decreased complement, thrombocytopenia, and leukopenia.
e) At least 1 of the following BILAG-based protocol-specific manifestations of SLE:
i) BILAG A or B grade in the Mucocutaneous body system. If a BILAG B grade for Mucocutaneous disease is due to mild skin eruption, the total score of the erythema and scale components of the CLASI disease activity must be ≥ 3 (excluding mucous membrane ulcerations and
nonscarring alopecia).
ii) Modified BILAG A or B score in the Musculoskeletal body system due to active polyarthritis defined as follows:
(1). BILAG A severe arthritis, manifested by observed active synovitis in ≥ 6 joints
• Hips, shoulders, neck, low back, and temporomandibular joint may not count toward the total number of joints with active synovitis
• There must be marked loss of functional range of movements and significant impairment of basic activities of daily living (ADLs), as follows:
o Impairment from arthritis must have been present on several days (ie,> 4 days) cumulatively over the past 4 weeks and must be
present at the time of the screening visit.
o Significant impairment of basic ADLs is defined as requiring the assistance of another person or an assistive device (at least 1
must be present and documented in source): ambulation, toileting, grooming including bathing, dressing, and feeding oneself (and not
responsive to corticosteroid up to 10 mg/day).
(2). BILAG B: moderate arthritis or tendonitis or tenosynovitis, defined as tendonitis/tenosynovitis or active synovitis in ≥ 3 joints
(observed or through history)
• Hips, shoulders, neck, low back, and temporomandibular joint may not count toward the total number of joints with active synovitis.
• There must be some loss of functional range of movements (due to arthritis) as manifested by difficulty in performing any one of the instrumental ADLs (such as cooking, driving, using the telephone or computer, shopping, cleaning, etc) that has been present on several
days (ie, > 4 days) over the last 4 weeks and is present at the time of the screening visit.
iii) If only 1 B and no A grade is present in the Mucocutaneous body system or in the Musculoskeletal body system due to arthritis, then at least 1 B grade must be present in one of the other body systems, for a total of 2 BILAG B body system grades.
3) Medications for SLE
a) Background therapy is required for ≥ 12 weeks before the screening visit and must be at a stable dose for ≥ 8 weeks before the
screening visit and remain stable until randomization and throughout study participation. Details for specific medications are as follows:
• Immunosuppressants (combinations of these are NOTpermitted) (as only one is allowed not a combination of 2 or 3 above of them):
o azathioprine (maximum 200 mg/day)
o 6-mercaptopurine (6-MP)
o methotrexate (MTX; maximum 25 mg/week; dose and route of administration of MTX may not be changed for 8 weeks before the screening
visit and throughout study participation)
o leflunomide
o mycophenolate mofetil/ mycophenolic acid (MMF). Note: Subjects who are receiving MMF may participate in the study only if
administered as a maintenance therapy and up to a maximum of 2 g/day (or equivalent); in subjects of African ancestry, 3 g/day (or
equivalent) is acceptable. Treatment may be interrupted due to neutropenia per the product label.
• Antimalarials: chloroquine, hydroxychloroquine, or quinacrine; monotherapy is permitted.
• Required discontinuation periods for other immunomodulatory drugs (eg, cyclosporine, tacrolimus, etc) or biologic drugs (eg,
rituximab, belimumab, tocilizumab, etc). If a drug is not specifically listed, consult the medical monitor for guidance. Usual
discontinuation periods are 4 weeks or 5 half-lives whichever is longer.
b) Corticosteroid (prednisone or equivalent) background therapy is permitted but not required. For subjects taking corticosteroid, the dose must be stable for ≥ 2 weeks before the screening visit, cannot exceed 30 mg/day at screening, and must remain stable until
randomization. Further specifications are as follows:
• Intramuscular, intra-articular, intrabursal, and intravenous (IV) corticosteroid use is prohibited within 6 weeks before screening.
• Topical corticosteroid use is permitted, but must follow a stable regimen throughout the study and cannot be used on an as-needed
basis.
• Inhaled corticosteroid for nonlupus conditions is permitted and will not count against the maximum corticosteroid dose.
• Modified-release corticosteroid formulations are prohibited.
c) Requirements for subjects who are receiving chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs: including marketed
cyclooxygenase-2 inhibitors) are as follows; exceptions or changes may be possible with approval by the medical monitor:
• Doses must be stable for 14 days before the screening visit and must remain stable until randomization and throughout the study.
• No more than 1 oral nonsteroidal anti-inflammatory drug may be used (at a stable dose) during the study, and may be combined with
topical NSAIDs.
• Use of 1 or more topical nonsteroidal anti-inflammatory drugs is permitted, but must follow a stable regimen throughout the study.
4) Age and Reproductive Status
a) Men and women aged 20 to 75 years, inclusive, at the time of screening
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of beta-human chorionic gonadotropin [β-HCG]) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) (BMS-986165 or placebo) plus 5 half-lives of study treatment (3 days) plus 30 days (duration of ovulatory cycle) for a
total of 33 days post- treatment completion.
e) Women of childbearing potential who are not heterosexually active are exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.
f) Investigators shall counsel women of childbearing potential and men who are sexually active with women of childbearing potential on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly
effective methods of contraception (which have a failure rate of < 1% when used consistently and correctly).
g) Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception
for the duration of treatment with study treatment BMS-986165 or placebo plus 5 half-lives of the study treatment (3 days) after the final
dose of study treatment.
h) Azoospermic males are exempt from contraceptive requirements. Women of childbearing potential who are continuously not
heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing.
i) Male subjects must be willing to refrain from sperm donation during the entire duration of treatment plus 5 half-lives of study
treatment (3 days) after the final dose of study treatment.
1) Signed Written Informed Consent
a) Willing to participate in the study and sign the informed consent form (ICF).
b) Willing and able to complete all study-specific procedures and visits.
2) SLE Disease Characteristics
a) Diagnosed ≥ 24 weeks before the screening visit
b) Meets the SLICC classification criteria for SLE.
c) One of the following: elevated antinuclear antibodies (ANA) ≥ 1:80 or positive anti-dsDNA (positive includes indeterminate results) or positive anti-Smith (anti-Sm) as determined by the central laboratory.
d) Total SLEDAI-2K score ≥ 6 points and clinical SLEDAI-2K score ≥ 4 points with joint involvement and/or rash
o Lupus headache, alopecia, organic brain syndrome, and mucosal ulcers cannot count toward the points required for screening at entry.
o Clinical SLEDAI-2K excludes laboratory abnormalities such as hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA,
decreased complement, thrombocytopenia, and leukopenia.
e) At least 1 of the following BILAG-based protocol-specific manifestations of SLE:
i) BILAG A or B grade in the Mucocutaneous body system. If a BILAG B grade for Mucocutaneous disease is due to mild skin eruption, the total score of the erythema and scale components of the CLASI disease activity must be ≥ 3 (excluding mucous membrane ulcerations and
nonscarring alopecia).
ii) Modified BILAG A or B score in the Musculoskeletal body system due to active polyarthritis defined as follows:
(1). BILAG A severe arthritis, manifested by observed active synovitis in ≥ 6 joints
• Hips, shoulders, neck, low back, and temporomandibular joint may not count toward the total number of joints with active synovitis
• There must be marked loss of functional range of movements and significant impairment of basic activities of daily living (ADLs), as follows:
o Impairment from arthritis must have been present on several days (ie,> 4 days) cumulatively over the past 4 weeks and must be
present at the time of the screening visit.
o Significant impairment of basic ADLs is defined as requiring the assistance of another person or an assistive device (at least 1
must be present and documented in source): ambulation, toileting, grooming including bathing, dressing, and feeding oneself (and not
responsive to corticosteroid up to 10 mg/day).
(2). BILAG B: moderate arthritis or tendonitis or tenosynovitis, defined as tendonitis/tenosynovitis or active synovitis in ≥ 3 joints
(observed or through history)
• Hips, shoulders, neck, low back, and temporomandibular joint may not count toward the total number of joints with active synovitis.
• There must be some loss of functional range of movements (due to arthritis) as manifested by difficulty in performing any one of the instrumental ADLs (such as cooking, driving, using the telephone or computer, shopping, cleaning, etc) that has been present on several
days (ie, > 4 days) over the last 4 weeks and is present at the time of the screening visit.
iii) If only 1 B and no A grade is present in the Mucocutaneous body system or in the Musculoskeletal body system due to arthritis, then at least 1 B grade must be present in one of the other body systems, for a total of 2 BILAG B body system grades.
3) Medications for SLE
a) Background therapy is required for ≥ 12 weeks before the screening visit and must be at a stable dose for ≥ 8 weeks before the
screening visit and remain stable until randomization and throughout study participation. Details for specific medications are as follows:
• Immunosuppressants (combinations of these are NOTpermitted) (as only one is allowed not a combination of 2 or 3 above of them):
o azathioprine (maximum 200 mg/day)
o 6-mercaptopurine (6-MP)
o methotrexate (MTX; maximum 25 mg/week; dose and route of administration of MTX may not be changed for 8 weeks before the screening
visit and throughout study participation)
o leflunomide
o mycophenolate mofetil/ mycophenolic acid (MMF). Note: Subjects who are receiving MMF may participate in the study only if
administered as a maintenance therapy and up to a maximum of 2 g/day (or equivalent); in subjects of African ancestry, 3 g/day (or
equivalent) is acceptable. Treatment may be interrupted due to neutropenia per the product label.
• Antimalarials: chloroquine, hydroxychloroquine, or quinacrine; monotherapy is permitted.
• Required discontinuation periods for other immunomodulatory drugs (eg, cyclosporine, tacrolimus, etc) or biologic drugs (eg,
rituximab, belimumab, tocilizumab, etc). If a drug is not specifically listed, consult the medical monitor for guidance. Usual
discontinuation periods are 4 weeks or 5 half-lives whichever is longer.
b) Corticosteroid (prednisone or equivalent) background therapy is permitted but not required. For subjects taking corticosteroid, the dose must be stable for ≥ 2 weeks before the screening visit, cannot exceed 30 mg/day at screening, and must remain stable until
randomization. Further specifications are as follows:
• Intramuscular, intra-articular, intrabursal, and intravenous (IV) corticosteroid use is prohibited within 6 weeks before screening.
• Topical corticosteroid use is permitted, but must follow a stable regimen throughout the study and cannot be used on an as-needed
basis.
• Inhaled corticosteroid for nonlupus conditions is permitted and will not count against the maximum corticosteroid dose.
• Modified-release corticosteroid formulations are prohibited.
c) Requirements for subjects who are receiving chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs: including marketed
cyclooxygenase-2 inhibitors) are as follows; exceptions or changes may be possible with approval by the medical monitor:
• Doses must be stable for 14 days before the screening visit and must remain stable until randomization and throughout the study.
• No more than 1 oral nonsteroidal anti-inflammatory drug may be used (at a stable dose) during the study, and may be combined with
topical NSAIDs.
• Use of 1 or more topical nonsteroidal anti-inflammatory drugs is permitted, but must follow a stable regimen throughout the study.
4) Age and Reproductive Status
a) Men and women aged 20 to 75 years, inclusive, at the time of screening
b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of beta-human chorionic gonadotropin [β-HCG]) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding
d) Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) (BMS-986165 or placebo) plus 5 half-lives of study treatment (3 days) plus 30 days (duration of ovulatory cycle) for a
total of 33 days post- treatment completion.
e) Women of childbearing potential who are not heterosexually active are exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section.
f) Investigators shall counsel women of childbearing potential and men who are sexually active with women of childbearing potential on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly
effective methods of contraception (which have a failure rate of < 1% when used consistently and correctly).
g) Men who are sexually active with women of childbearing potential must agree to follow instructions for method(s) of contraception
for the duration of treatment with study treatment BMS-986165 or placebo plus 5 half-lives of the study treatment (3 days) after the final
dose of study treatment.
h) Azoospermic males are exempt from contraceptive requirements. Women of childbearing potential who are continuously not
heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing.
i) Male subjects must be willing to refrain from sperm donation during the entire duration of treatment plus 5 half-lives of study
treatment (3 days) after the final dose of study treatment.
Exclusion Criteria
Exclusion Criteria
1) Target Disease Exceptions
a) Drug-induced SLE
b) Subjects with other autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Subjects with type I autoimmune diabetes mellitus, thyroid autoimmune disease, or secondary Sjögren’s syndrome are not excluded.
c) Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue disease are excluded. Subjects with an overlap
syndrome of SLE with RA are not excluded as long as they meet the criteria for the classification of SLE as outlined in the inclusion
criteria (Inclusion criteria 2).
d) Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose (eg, if on Coumadin, an
international normalized ratio [INR] target 2 to 3 or as appropriate for the clinical situation) are allowed if this is not the sole or the predominant feature of their SLE. Subjects with a serious thrombotic event (eg, pulmonary embolism, stroke, deep vein thrombosis) or
unexplained pregnancy loss within 1 year before the screening visit are excluded. Subjects with a history of catastrophic antiphospholipid
syndrome or saddle embolism are excluded. Subjects with a history of 3 or more unexplained consecutive pregnancy losses would also be
excluded.
e) Subjects with active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria are excluded, with the exception of subjects with mononeuritis multiplex and polyneuropathy, which are allowed.
f) Subjects with active, severe lupus nephritis (World Health Organization Class III, IV) that requires or may require treatment with
cytotoxic agents or high-dose corticosteroid are excluded. Subjects with prior, controlled renal disease with serum creatinine ≤ 2× upper
limit of normal (ULN) and either residual proteinuria up to 3 g/day or a urine protein/creatinine ratio of 3 mg/mg or 339 mg/mmol are
allowed. Control of renal disease must be documented with at least 2 measurements of proteinuria or urine protein/creatinine ratio over the past 6 months.
2) Other Medical Conditions and History
a) Women who are pregnant or breastfeeding
b) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal,
endocrine, pulmonary, immunologic, psychiatric) or local active infection/infectious illness that, in the investigator’s judgment, will
substantially increase the risk to the subject if he or she participates in the study.
c) Any major surgery within the last 30 days before the first dose of study treatment, or any surgery planned during the course of
the study.
d) Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than adequately treated cutaneous
basal cell or squamous cell carcinoma with no evidence of recurrence)
e) Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) or any recent onset of heart failure
resulting in NYHA Class III/IV symptoms
f) Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and/or any history of significant cerebrovascular
disease within 24 weeks before screening
g) Current or recent (within 3 months before randomization) gastrointestinal disease, including gastrointestinal surgery, that could impact the absorption of study treatment
h) Subjects with non-SLE concomitant illness that, in the opinion of the investigator, is likely to require additional systemic
glucocorticosteroid therapy during the study (eg, asthma).
i) Significant blood loss (> 500 mL) or blood transfusion within 4 weeks before randomization
j) Inability to tolerate oral medication
k) Inability to undergo venipuncture and/or tolerate venous access
l) Recent (within 6 months before randomization) drug or alcohol abuse as defined by the Diagnostic Criteria for Drug and Alcohol
Abuse in the Diagnostic and Statistical Manual of Mental Disorders IV
m) Any other sound medical, psychiatric, and/or social reason as determined by the Investigator
3) Prior and Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments. Inability to comply with discontinuation requirements.
b) Taking more than 1 immunosuppressant.
c) Prior exposure to Tyk2 inhibitors
d) Prior exposure to anifrolumab, rontalizumab, or ustekinumab
e) Other investigational agents must be discontinued at least 12 weeks or 5 half-lives before screening, whichever is longer.
4) Findings Related to Possible Infection
a) Evidence of active or latent tuberculosis, as follows:
• Positive chest X-ray for evidence of active pulmonary tuberculosis within 6 months before screening
• Subjects with negative chest X-ray within 6 months before screening may be eligible provided any of the following apply:
o negative IFN gamma release assay
o positive IFN gamma release assay and no symptoms of active tuberculosis, and have previously (within 5 years) received adequate
documented treatment for latent TB, per investigator’s medical judgment
o positive IFN gamma release assay and no symptoms of active tuberculosis, but have NOT previously (within 5 years) received adequate documented treatment, per investigator’s medical judgement; subject must initiate prophylactic treatment per local guidelines and may
rescreen after 1 month of treatment (if subject is enrolled, the prophylactic tuberculosis treatment must continue throughout the study)
b) Hepatitis C, hepatitis B, or human immunodeficiency virus (HIV) infection as demonstrated by a positive blood screen for hepatitis C antibody (anti-HCV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or HIV-1 and -2 antibody. Subjects who have been vaccinated for hepatitis B (hepatitis B surface antibody [anti-HBs] positive) are not excluded. Note that anti-HBs is not requested.
Note: Subjects who are newly found to be HIV-positive should be directed to appropriate follow-up care. If your HIV test result is positive (including false positive), the trial hospital and trial physician will provide you with subsequent medical referral or consultation and
will report to the competent authority as required by the law.
c) Currently on any therapy for chronic infection (eg, pneumocystis, cytomegalovirus [CMV], herpes simplex, herpes zoster, invasive
bacterial or fungal infections, or atypical mycobacteria)
d) History of congenital or acquired immunodeficiency
e) Known active infection, or any major episode of infection requiring hospitalization or treatment with parenteral (intramuscular or
IV) antimicrobial agents (eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 30 days of randomization, or completion of oral antimicrobial agents within 2 weeks of randomization
f) Previous history of herpes zoster, herpes simplex, or influenza infection within 12 weeks before randomization or a history of disseminated/complicated herpes zoster infection (multidermatomal involvement, ophthalmic zoster, central nervous system involvement, or post-herpetic neuralgia)
g) Administration of a live vaccine within 90 days or an inactivated vaccine within 30 days before randomization. Heat-killed, or
otherwise inactivated or protein vaccines (eg, influenza and pneumococcal vaccines) may be received at any time on study. Furthermore, live vaccines should not be used during treatment or within the 2 months following last dose, and any other inactivated vaccines (eg, tetanus,
etc) should be used according to local guidelines during the TP.
5) Physical and Laboratory Test Findings
a) Clinically significant abnormalities on chest X-ray or ECG
b) Clinically significant abnormalities in laboratory tests including the following:
i) Serum alanine aminotransferase (ALT) > 2× ULN, unless explicitly related to lupus based on the investigator’s judgment
ii) Serum aspartate aminotransferase (AST) > 2× ULN, unless explicitly related to lupus based on the investigator’s judgment
iii) Serum total bilirubin > 1.5× ULN, unless explicitly related to lupus based on the investigator’s judgment
iv) Hemoglobin < 8 g/dL (80 g/L) or, if due to hemolytic anemia related to SLE, < 7 g/dL (70 g/L)
v) Proteinuria > 3.0 g/day (3000 mg/day) or equivalent level of proteinuria as assessed by urine protein/creatinine ratio (3 mg/mg or 339 mg/mmol)
vi) Estimated glomerular filtration rate < 30 mL/min
vii) Absolute white blood cell count < 1.2× 103/µL (1.2× 109/L)
viii) Platelet count < 50× 103/µL (50× 109/L)
ix) Abnormal free thyroxine (T4); if If a subject has abnormal thyroid stimulating hormone (TSH; abnormal relative to laboratory normal range) at screening, free T4 will be assessed. Those with abnormal free T4 (relative to laboratory normal range) will be excluded unless
they have a prior diagnosis of a thyroid disorder and are currently receiving thyroid replacement therapy; these subjects may rescreen after a minimum of 6 weeks after adjustment of thyroid hormone replacement therapy. Such cases should be discussed with the medical monitor.
c) Any other significant laboratory or procedure abnormalities that, in the opinion of the investigator, might pose unacceptable risk
to the subject during the study
6) Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. Note: under certain specific circumstances, a person who has been
imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Bristol-Myers Squibb (BMS) approval is
required.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
c) Inability to comply with the study protocol
1) Target Disease Exceptions
a) Drug-induced SLE
b) Subjects with other autoimmune diseases (eg, multiple sclerosis, psoriasis, inflammatory bowel disease, etc) are excluded. Subjects with type I autoimmune diabetes mellitus, thyroid autoimmune disease, or secondary Sjögren’s syndrome are not excluded.
c) Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue disease are excluded. Subjects with an overlap
syndrome of SLE with RA are not excluded as long as they meet the criteria for the classification of SLE as outlined in the inclusion
criteria (Inclusion criteria 2).
d) Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose (eg, if on Coumadin, an
international normalized ratio [INR] target 2 to 3 or as appropriate for the clinical situation) are allowed if this is not the sole or the predominant feature of their SLE. Subjects with a serious thrombotic event (eg, pulmonary embolism, stroke, deep vein thrombosis) or
unexplained pregnancy loss within 1 year before the screening visit are excluded. Subjects with a history of catastrophic antiphospholipid
syndrome or saddle embolism are excluded. Subjects with a history of 3 or more unexplained consecutive pregnancy losses would also be
excluded.
e) Subjects with active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria are excluded, with the exception of subjects with mononeuritis multiplex and polyneuropathy, which are allowed.
f) Subjects with active, severe lupus nephritis (World Health Organization Class III, IV) that requires or may require treatment with
cytotoxic agents or high-dose corticosteroid are excluded. Subjects with prior, controlled renal disease with serum creatinine ≤ 2× upper
limit of normal (ULN) and either residual proteinuria up to 3 g/day or a urine protein/creatinine ratio of 3 mg/mg or 339 mg/mmol are
allowed. Control of renal disease must be documented with at least 2 measurements of proteinuria or urine protein/creatinine ratio over the past 6 months.
2) Other Medical Conditions and History
a) Women who are pregnant or breastfeeding
b) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal,
endocrine, pulmonary, immunologic, psychiatric) or local active infection/infectious illness that, in the investigator’s judgment, will
substantially increase the risk to the subject if he or she participates in the study.
c) Any major surgery within the last 30 days before the first dose of study treatment, or any surgery planned during the course of
the study.
d) Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than adequately treated cutaneous
basal cell or squamous cell carcinoma with no evidence of recurrence)
e) Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) or any recent onset of heart failure
resulting in NYHA Class III/IV symptoms
f) Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and/or any history of significant cerebrovascular
disease within 24 weeks before screening
g) Current or recent (within 3 months before randomization) gastrointestinal disease, including gastrointestinal surgery, that could impact the absorption of study treatment
h) Subjects with non-SLE concomitant illness that, in the opinion of the investigator, is likely to require additional systemic
glucocorticosteroid therapy during the study (eg, asthma).
i) Significant blood loss (> 500 mL) or blood transfusion within 4 weeks before randomization
j) Inability to tolerate oral medication
k) Inability to undergo venipuncture and/or tolerate venous access
l) Recent (within 6 months before randomization) drug or alcohol abuse as defined by the Diagnostic Criteria for Drug and Alcohol
Abuse in the Diagnostic and Statistical Manual of Mental Disorders IV
m) Any other sound medical, psychiatric, and/or social reason as determined by the Investigator
3) Prior and Concomitant Therapy
a) Inability to comply with restrictions and prohibited treatments. Inability to comply with discontinuation requirements.
b) Taking more than 1 immunosuppressant.
c) Prior exposure to Tyk2 inhibitors
d) Prior exposure to anifrolumab, rontalizumab, or ustekinumab
e) Other investigational agents must be discontinued at least 12 weeks or 5 half-lives before screening, whichever is longer.
4) Findings Related to Possible Infection
a) Evidence of active or latent tuberculosis, as follows:
• Positive chest X-ray for evidence of active pulmonary tuberculosis within 6 months before screening
• Subjects with negative chest X-ray within 6 months before screening may be eligible provided any of the following apply:
o negative IFN gamma release assay
o positive IFN gamma release assay and no symptoms of active tuberculosis, and have previously (within 5 years) received adequate
documented treatment for latent TB, per investigator’s medical judgment
o positive IFN gamma release assay and no symptoms of active tuberculosis, but have NOT previously (within 5 years) received adequate documented treatment, per investigator’s medical judgement; subject must initiate prophylactic treatment per local guidelines and may
rescreen after 1 month of treatment (if subject is enrolled, the prophylactic tuberculosis treatment must continue throughout the study)
b) Hepatitis C, hepatitis B, or human immunodeficiency virus (HIV) infection as demonstrated by a positive blood screen for hepatitis C antibody (anti-HCV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or HIV-1 and -2 antibody. Subjects who have been vaccinated for hepatitis B (hepatitis B surface antibody [anti-HBs] positive) are not excluded. Note that anti-HBs is not requested.
Note: Subjects who are newly found to be HIV-positive should be directed to appropriate follow-up care. If your HIV test result is positive (including false positive), the trial hospital and trial physician will provide you with subsequent medical referral or consultation and
will report to the competent authority as required by the law.
c) Currently on any therapy for chronic infection (eg, pneumocystis, cytomegalovirus [CMV], herpes simplex, herpes zoster, invasive
bacterial or fungal infections, or atypical mycobacteria)
d) History of congenital or acquired immunodeficiency
e) Known active infection, or any major episode of infection requiring hospitalization or treatment with parenteral (intramuscular or
IV) antimicrobial agents (eg, antibiotics, antiviral, antifungal, or antiparasitic agents) within 30 days of randomization, or completion of oral antimicrobial agents within 2 weeks of randomization
f) Previous history of herpes zoster, herpes simplex, or influenza infection within 12 weeks before randomization or a history of disseminated/complicated herpes zoster infection (multidermatomal involvement, ophthalmic zoster, central nervous system involvement, or post-herpetic neuralgia)
g) Administration of a live vaccine within 90 days or an inactivated vaccine within 30 days before randomization. Heat-killed, or
otherwise inactivated or protein vaccines (eg, influenza and pneumococcal vaccines) may be received at any time on study. Furthermore, live vaccines should not be used during treatment or within the 2 months following last dose, and any other inactivated vaccines (eg, tetanus,
etc) should be used according to local guidelines during the TP.
5) Physical and Laboratory Test Findings
a) Clinically significant abnormalities on chest X-ray or ECG
b) Clinically significant abnormalities in laboratory tests including the following:
i) Serum alanine aminotransferase (ALT) > 2× ULN, unless explicitly related to lupus based on the investigator’s judgment
ii) Serum aspartate aminotransferase (AST) > 2× ULN, unless explicitly related to lupus based on the investigator’s judgment
iii) Serum total bilirubin > 1.5× ULN, unless explicitly related to lupus based on the investigator’s judgment
iv) Hemoglobin < 8 g/dL (80 g/L) or, if due to hemolytic anemia related to SLE, < 7 g/dL (70 g/L)
v) Proteinuria > 3.0 g/day (3000 mg/day) or equivalent level of proteinuria as assessed by urine protein/creatinine ratio (3 mg/mg or 339 mg/mmol)
vi) Estimated glomerular filtration rate < 30 mL/min
vii) Absolute white blood cell count < 1.2× 103/µL (1.2× 109/L)
viii) Platelet count < 50× 103/µL (50× 109/L)
ix) Abnormal free thyroxine (T4); if If a subject has abnormal thyroid stimulating hormone (TSH; abnormal relative to laboratory normal range) at screening, free T4 will be assessed. Those with abnormal free T4 (relative to laboratory normal range) will be excluded unless
they have a prior diagnosis of a thyroid disorder and are currently receiving thyroid replacement therapy; these subjects may rescreen after a minimum of 6 weeks after adjustment of thyroid hormone replacement therapy. Such cases should be discussed with the medical monitor.
c) Any other significant laboratory or procedure abnormalities that, in the opinion of the investigator, might pose unacceptable risk
to the subject during the study
6) Allergies and Adverse Drug Reaction
a) History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated. Note: under certain specific circumstances, a person who has been
imprisoned may be included or permitted to continue as a subject. Strict conditions apply and Bristol-Myers Squibb (BMS) approval is
required.
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
c) Inability to comply with the study protocol
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
participants
