Clinical Trials List
Protocol NumberALX0061-C204
NCT Number(ClinicalTrials.gov Identfier)NCT02437890
2015-09-01 - 2018-07-31
Phase II
Terminated5
ICD-10M32.9
Systemic lupus erythematosus, unspecified
ICD-10M32
Systemic lupus erythematosus (SLE)
ICD-9710.0
Systemic lupus erythematosus
A Phase II Multicenter, Randomized, Double-blind, Placebo controlled, Dose-range Finding Study to Evaluate the Safety and Efficacy of ALX 0061 Administered Subcutaneously in Subjects with Moderate to Severe Active Systemic Lupus Erythematosus
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
Ablynx NV
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Po-Hao Huang Division of Rheumatology
- 洪偉哲 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Chang-Fu Kuo Division of Rheumatology
- Ping-Han Tsai Division of Rheumatology
- 陳彥輔 Division of Rheumatology
- Yao-Fan Fang Division of Rheumatology
- TianMing Zhan Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Principal Investigator
Co-Principal Investigator
- Wen Chan Tsai 未分科
Audit
None
Co-Principal Investigator
- 郭佑民 Division of Rheumatology
- PING-NING HSU Division of Rheumatology
- SONG-CHOU HSIEH Division of Rheumatology
- CHIEH-YU SHEN Division of Rheumatology
- KO-JEN LI Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Systemic Lupus Erythematosus (SLE)
Objectives
Primary objective:
To assess the efficacy and safety of different dose regimens of ALX-0061 administered
subcutaneously (s.c.) to subjects with moderate to severe active, seropositive SLE
compared to placebo.
Secondary objectives:
To assess the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, flare
rate, steroid reduction and health-related quality of life, with different dose regimens of
ALX-0061.
Test Drug
ALX-0061
Active Ingredient
ALX-0061 Nanobody
Dosage Form
Injection
Dosage
150 mg / ml
Endpoints
Efficacy evaluation
Primary endpoint: The primary endpoint is the percentage of subjects who achieved a
response at Week 24 according to the composite mBICLA (BILAG-based Combined Lupus
Assessment) score. mBICLA responders are defined as subjects who meet all of the
following criteria:
(1) BILAG-2004 improvement: all A scores at baseline improved to B/C/D, and all B scores
improved to C or D.
(2) no worsening in disease activity: no new BILAG-2004 A scores and ≤1 new B score.
(3) no worsening of total mSLEDAI-2K score from baseline.
(4) no significant deterioration (< 10% worsening) in Physician global assessment (PGA).
(5) no treatment failure (i.e., new or increased immunosuppressives or anti-malarials; or
non-protocol allowed increased oral or parenteral corticosteroids; or premature
discontinuation from study treatment).
A modified SLEDAI-2K index (mSLEDAI-2K) will be derived from the standard index by
omitting 1 of the standard items (low complement).
Safety
Safety assessments will include:
Physical examination.
Vital signs measurement.
Electrocardiogram (ECG).
Blood chemistry (including liver enzymes and lipids), hematology (including neutrophils
and platelets) and coagulation parameters. Lupus anti-coagulant (LA), anti-cardiolipin
(aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies will be evaluated at screening and
Week 24.
Adverse events (AEs) (including local tolerability and hypersensitivity reactions) and
serious AEs.
Primary endpoint: The primary endpoint is the percentage of subjects who achieved a
response at Week 24 according to the composite mBICLA (BILAG-based Combined Lupus
Assessment) score. mBICLA responders are defined as subjects who meet all of the
following criteria:
(1) BILAG-2004 improvement: all A scores at baseline improved to B/C/D, and all B scores
improved to C or D.
(2) no worsening in disease activity: no new BILAG-2004 A scores and ≤1 new B score.
(3) no worsening of total mSLEDAI-2K score from baseline.
(4) no significant deterioration (< 10% worsening) in Physician global assessment (PGA).
(5) no treatment failure (i.e., new or increased immunosuppressives or anti-malarials; or
non-protocol allowed increased oral or parenteral corticosteroids; or premature
discontinuation from study treatment).
A modified SLEDAI-2K index (mSLEDAI-2K) will be derived from the standard index by
omitting 1 of the standard items (low complement).
Safety
Safety assessments will include:
Physical examination.
Vital signs measurement.
Electrocardiogram (ECG).
Blood chemistry (including liver enzymes and lipids), hematology (including neutrophils
and platelets) and coagulation parameters. Lupus anti-coagulant (LA), anti-cardiolipin
(aCL) and anti-β2-glycoprotein I (β2-GPI) antibodies will be evaluated at screening and
Week 24.
Adverse events (AEs) (including local tolerability and hypersensitivity reactions) and
serious AEs.
Inclution Criteria
Inclusion Criteria:
Each subject must satisfy the following criteria at screening and baseline to be enrolled in
the study:
1. Male or female adults ≥ 18 years and < 65 years of age at the time of signing the
informed consent form (ICF). The minimum age for adults will depend on local
regulations.
2. Have a diagnosis of SLE and fulfill the 1997 American College of Rheumatology (ACR)
or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria
for at least 6 months prior to screening.
3. Have moderate to severe active SLE, for the purpose of this study defined by a 2000
SLE disease activity index (SLEDAI-2K) score ≥ 6 at screening.
4. Have at least one A or one B score on the revised 2004 British Isles Lupus Assessment
Group (BILAG-2004) criteria for the mucocutaneous and/or musculoskeletal system.
5. Have seropositive disease at screening for antinuclear antibodies (ANA ≥ 1:80) and/or
anti-dsDNA (≥ 30 IU/mL) measured at the central laboratory.
6. Subject at least must be on one or more of the following treatments for SLE:
a. If subject is on oral corticosteroids, the dose should be equivalent to a maximum
dose of 25 mg of prednisone/day and stable for at least 4 weeks prior to baseline.
b. If subject is on antimalarials, he or she must have received antimalarials for at least
12 weeks with a stable dose of max. 400 mg/day for at least 4 weeks prior to
baseline.
c. If subject is on immunosuppressants: azathioprine (max. 150 mg/day),
mycophenolate mofetil (max. 1.5 g/day), methotrexate (max. 25 mg/day),
cyclosporine (max. 200 mg), leflunomide (max. 20 mg/day), treatment duration
must be at least 12 weeks with a stable dose for at least 4 weeks prior to baseline;
either alone or in combination with corticosteroids and/or hydroxychloroquine.
7. If immunosuppressants were previously given but have been stopped, the last dose
should have been received more than 4 weeks prior to baseline; for leflunomide and
hydroxychloroquine, a leflunomide or hydroxychloroquine treatment-free period of at
least 12 weeks should be respected (unless an adequate cholestyramine wash-out was
done for leflunomide).
8. If subject is on angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor
blocker, the dose should have been stable for 4 weeks prior to baseline.
9. Chest radiograph performed within 12 weeks prior to the screening visit (or performed
during the screening period) documenting no evidence of malignancy, infection, or
abnormalities suggestive of tuberculosis (TB; report must be obtained and available in
the subject’s study file prior to baseline).
10. 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 with a history of latent TB and documentation of having completed
appropriate treatment for latent TB prior to screening. It is the responsibility of the
Investigator to verify the adequacy of previous anti-TB treatment and provide
appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination during screening.
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 specialized in TB to undergo additional
evaluation and, if warranted, receive appropriate treatment.
d. Have a negative interferon gamma release assay (IGRA) screening test result. A
subject whose initial IGRA test result is indeterminate should have the test repeated
while still fulfilling the other TB criteria for inclusion. The test should not be repeated
in case other risk factors for TB are present. In case the test is again indeterminate,
the subject will be excluded. In case of a positive IGRA test result due to previous
latent TB, the subject is eligible if adequate documentation of completed anti-TB
treatment prior to screening is available.
e. Have a chest radiograph, read by a qualified radiologist, whose diagnostic
assessment is consistent with no evidence of current active TB or old inactive TB,
and taken within 12 weeks prior to screening as part of standard of care or during
the screening period. In case local regulations do not allow radiographs during the
study, a radiograph as part of standard of care should be available prior to screening.
11. Female subjects of childbearing potential (excluding postmenopausal women, sterilized,
ovariectomized and hysterectomized women) must have a negative pregnancy test and
must agree to use two generally accepted adequate contraceptive methods (1 highly
effective and 1 barrier method e.g., hormonal contraception in combination with
condom by partner) from screening until at least 3 months after last dosing.
Male subjects must use condoms for the duration of the study and for at least 3 months
after last dosing.
12. Capability to comprehend and willingness to sign an ICF, which must be obtained prior
to any study-related procedures (vulnerable subjects will be excluded, except subjects
from ethnic minority groups who may participate).
13. An understanding, ability and willingness to adhere to the study visit schedule and other
protocol requirements.
Each subject must satisfy the following criteria at screening and baseline to be enrolled in
the study:
1. Male or female adults ≥ 18 years and < 65 years of age at the time of signing the
informed consent form (ICF). The minimum age for adults will depend on local
regulations.
2. Have a diagnosis of SLE and fulfill the 1997 American College of Rheumatology (ACR)
or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria
for at least 6 months prior to screening.
3. Have moderate to severe active SLE, for the purpose of this study defined by a 2000
SLE disease activity index (SLEDAI-2K) score ≥ 6 at screening.
4. Have at least one A or one B score on the revised 2004 British Isles Lupus Assessment
Group (BILAG-2004) criteria for the mucocutaneous and/or musculoskeletal system.
5. Have seropositive disease at screening for antinuclear antibodies (ANA ≥ 1:80) and/or
anti-dsDNA (≥ 30 IU/mL) measured at the central laboratory.
6. Subject at least must be on one or more of the following treatments for SLE:
a. If subject is on oral corticosteroids, the dose should be equivalent to a maximum
dose of 25 mg of prednisone/day and stable for at least 4 weeks prior to baseline.
b. If subject is on antimalarials, he or she must have received antimalarials for at least
12 weeks with a stable dose of max. 400 mg/day for at least 4 weeks prior to
baseline.
c. If subject is on immunosuppressants: azathioprine (max. 150 mg/day),
mycophenolate mofetil (max. 1.5 g/day), methotrexate (max. 25 mg/day),
cyclosporine (max. 200 mg), leflunomide (max. 20 mg/day), treatment duration
must be at least 12 weeks with a stable dose for at least 4 weeks prior to baseline;
either alone or in combination with corticosteroids and/or hydroxychloroquine.
7. If immunosuppressants were previously given but have been stopped, the last dose
should have been received more than 4 weeks prior to baseline; for leflunomide and
hydroxychloroquine, a leflunomide or hydroxychloroquine treatment-free period of at
least 12 weeks should be respected (unless an adequate cholestyramine wash-out was
done for leflunomide).
8. If subject is on angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor
blocker, the dose should have been stable for 4 weeks prior to baseline.
9. Chest radiograph performed within 12 weeks prior to the screening visit (or performed
during the screening period) documenting no evidence of malignancy, infection, or
abnormalities suggestive of tuberculosis (TB; report must be obtained and available in
the subject’s study file prior to baseline).
10. 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 with a history of latent TB and documentation of having completed
appropriate treatment for latent TB prior to screening. It is the responsibility of the
Investigator to verify the adequacy of previous anti-TB treatment and provide
appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination during screening.
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 specialized in TB to undergo additional
evaluation and, if warranted, receive appropriate treatment.
d. Have a negative interferon gamma release assay (IGRA) screening test result. A
subject whose initial IGRA test result is indeterminate should have the test repeated
while still fulfilling the other TB criteria for inclusion. The test should not be repeated
in case other risk factors for TB are present. In case the test is again indeterminate,
the subject will be excluded. In case of a positive IGRA test result due to previous
latent TB, the subject is eligible if adequate documentation of completed anti-TB
treatment prior to screening is available.
e. Have a chest radiograph, read by a qualified radiologist, whose diagnostic
assessment is consistent with no evidence of current active TB or old inactive TB,
and taken within 12 weeks prior to screening as part of standard of care or during
the screening period. In case local regulations do not allow radiographs during the
study, a radiograph as part of standard of care should be available prior to screening.
11. Female subjects of childbearing potential (excluding postmenopausal women, sterilized,
ovariectomized and hysterectomized women) must have a negative pregnancy test and
must agree to use two generally accepted adequate contraceptive methods (1 highly
effective and 1 barrier method e.g., hormonal contraception in combination with
condom by partner) from screening until at least 3 months after last dosing.
Male subjects must use condoms for the duration of the study and for at least 3 months
after last dosing.
12. Capability to comprehend and willingness to sign an ICF, which must be obtained prior
to any study-related procedures (vulnerable subjects will be excluded, except subjects
from ethnic minority groups who may participate).
13. An understanding, ability and willingness to adhere to the study visit schedule and other
protocol requirements.
Exclusion Criteria
Exclusion Criteria:
Subject meeting the following criteria at screening and baseline will not be enrolled in the
study:
1. Have an A score on the revised BILAG-2004 other than in the mucocutaneous and/or
musculoskeletal system at screening.
2. Have a systemic inflammatory disease other than SLE, including but not limited to
psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis or Lyme disease.
3. Infection treated with intravenous (i.v.) antibiotics, i.v. antivirals, or i.v. antifungals
within 4 weeks prior to baseline or oral antibiotics, oral antivirals, or oral antifungals
within 2 weeks prior to baseline.
4. Any active or recurrent viral infection that based on the Investigator´ s clinical
assessment makes the subject unsuitable for the study, such as current
Cytomegalovirus (CMV) or Epstein-Barr Virus (EBV) infection or recurrent /
disseminated herpes zoster.
5. Have a history of, or current, class III or IV congestive heart failure (CHF), as defined
by the New-York Heart Association; history of unstable angina pectoris, myocardial
infarction, cerebrovascular accident, thromboembolic event within 12 months before
screening.
6. Have active lupus nephritis requiring cyclophosphamide or mycophenolate mofetil more
than 1,5 g/day or other therapy not permitted by the protocol.
7. Have lupus-related central neurological problems (including lupus headache) or severe
central nervous system (CNS) disease.
8. Have drug-induced lupus.
9. Have a history of demyelinating diseases such as multiple sclerosis.
10. History of diverticulitis or symptoms of acute diverticulitis with confirmatory imaging
(i.e., CT scan).
11. Any history of malignancy or lymphoproliferative disease, except for successfullytreated non-melanoma skin cancer or resected cervical carcinoma in situ.
12. Have a transplanted organ or received stem cell transplantation.
13. Major surgery (including joint surgery) within 8 weeks prior to screening or
hospitalization for a clinically relevant event within the 4 weeks prior to screening or
planned major surgery during study or within 3 months after study end.
14. Have been treated with i.v. immunoglobulins, cyclophosphamide or tacrolimus within
12 months prior to baseline.
15. Have received i.v., intra-articular (i.a.), intramuscular (i.m.) or high dose (> 25 mg/day)
oral corticosteroids during the 4 weeks prior to baseline.
16. Have a known hypersensitivity to the active product or any excipient of the study drug.
17. Have received approved or investigational biological therapies within 6 months or
5 half-lives of the concerned therapy (whichever is longer) prior to baseline.
18. Have received non-biological investigational therapies within 4 weeks or 5 half-lives of
the concerned therapy (whichever is longer) prior to baseline.
19. Have received prior therapy blocking the IL-6 pathway, such as but not limited to
ALX-0061, sirukumab, tocilizumab, sarilumab, clazakizumab, olokizumab, or Janus
kinase (JAK) inhibitors at any time.
20. Abnormality in screening laboratory test results:
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
≥ 1.5 times the upper limit of normal (ULN).
b. Hemoglobin ≤ 85 g/L (8.5 g/dL).
c. Platelet count ≤ 75 x 109
/L (75,000 cells/mm³).
d. White blood cell count ≤ 2.2 x 109
/L (2,200 cells/mm³).
e. Neutrophils: ≤ 1.5 X 109
/L.
f. Estimated proteinuria > 1 g/day measured by spot urine protein to creatinine ratio of
1.
g. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m² (based on the
‘modification of diet in renal disease’ [MDRD] formula).
h. Any other clinically significant abnormal screening laboratory results as evaluated by
the Investigator.
21. Positive screening for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
22. Known history or presence of alcohol or drug abuse.
23. Blood donation (> 500 mL) or a comparable blood loss within 3 months prior to
baseline.
24. Planned donation of germ cells, blood, organs, bone marrow during the course of the
study or within 6 months thereafter.
25. Female subjects who are planning to become pregnant during the study or within
3 months after last dosing or male subjects who are considering fathering a child during
the study and within 3 months after last dosing.
26. Pregnant woman or female subjects who are breastfeeding.
27. History of anaphylactic reactions.
28. Administration of a live, attenuated vaccine within 3 months before dosing with
ALX-0061, or anticipation that such a live attenuated vaccine will be required during the
study or within 6 months after last dosing.
29. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate
for the study.
Subject meeting the following criteria at screening and baseline will not be enrolled in the
study:
1. Have an A score on the revised BILAG-2004 other than in the mucocutaneous and/or
musculoskeletal system at screening.
2. Have a systemic inflammatory disease other than SLE, including but not limited to
psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis or Lyme disease.
3. Infection treated with intravenous (i.v.) antibiotics, i.v. antivirals, or i.v. antifungals
within 4 weeks prior to baseline or oral antibiotics, oral antivirals, or oral antifungals
within 2 weeks prior to baseline.
4. Any active or recurrent viral infection that based on the Investigator´ s clinical
assessment makes the subject unsuitable for the study, such as current
Cytomegalovirus (CMV) or Epstein-Barr Virus (EBV) infection or recurrent /
disseminated herpes zoster.
5. Have a history of, or current, class III or IV congestive heart failure (CHF), as defined
by the New-York Heart Association; history of unstable angina pectoris, myocardial
infarction, cerebrovascular accident, thromboembolic event within 12 months before
screening.
6. Have active lupus nephritis requiring cyclophosphamide or mycophenolate mofetil more
than 1,5 g/day or other therapy not permitted by the protocol.
7. Have lupus-related central neurological problems (including lupus headache) or severe
central nervous system (CNS) disease.
8. Have drug-induced lupus.
9. Have a history of demyelinating diseases such as multiple sclerosis.
10. History of diverticulitis or symptoms of acute diverticulitis with confirmatory imaging
(i.e., CT scan).
11. Any history of malignancy or lymphoproliferative disease, except for successfullytreated non-melanoma skin cancer or resected cervical carcinoma in situ.
12. Have a transplanted organ or received stem cell transplantation.
13. Major surgery (including joint surgery) within 8 weeks prior to screening or
hospitalization for a clinically relevant event within the 4 weeks prior to screening or
planned major surgery during study or within 3 months after study end.
14. Have been treated with i.v. immunoglobulins, cyclophosphamide or tacrolimus within
12 months prior to baseline.
15. Have received i.v., intra-articular (i.a.), intramuscular (i.m.) or high dose (> 25 mg/day)
oral corticosteroids during the 4 weeks prior to baseline.
16. Have a known hypersensitivity to the active product or any excipient of the study drug.
17. Have received approved or investigational biological therapies within 6 months or
5 half-lives of the concerned therapy (whichever is longer) prior to baseline.
18. Have received non-biological investigational therapies within 4 weeks or 5 half-lives of
the concerned therapy (whichever is longer) prior to baseline.
19. Have received prior therapy blocking the IL-6 pathway, such as but not limited to
ALX-0061, sirukumab, tocilizumab, sarilumab, clazakizumab, olokizumab, or Janus
kinase (JAK) inhibitors at any time.
20. Abnormality in screening laboratory test results:
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
≥ 1.5 times the upper limit of normal (ULN).
b. Hemoglobin ≤ 85 g/L (8.5 g/dL).
c. Platelet count ≤ 75 x 109
/L (75,000 cells/mm³).
d. White blood cell count ≤ 2.2 x 109
/L (2,200 cells/mm³).
e. Neutrophils: ≤ 1.5 X 109
/L.
f. Estimated proteinuria > 1 g/day measured by spot urine protein to creatinine ratio of
1.
g. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m² (based on the
‘modification of diet in renal disease’ [MDRD] formula).
h. Any other clinically significant abnormal screening laboratory results as evaluated by
the Investigator.
21. Positive screening for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
22. Known history or presence of alcohol or drug abuse.
23. Blood donation (> 500 mL) or a comparable blood loss within 3 months prior to
baseline.
24. Planned donation of germ cells, blood, organs, bone marrow during the course of the
study or within 6 months thereafter.
25. Female subjects who are planning to become pregnant during the study or within
3 months after last dosing or male subjects who are considering fathering a child during
the study and within 3 months after last dosing.
26. Pregnant woman or female subjects who are breastfeeding.
27. History of anaphylactic reactions.
28. Administration of a live, attenuated vaccine within 3 months before dosing with
ALX-0061, or anticipation that such a live attenuated vaccine will be required during the
study or within 6 months after last dosing.
29. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate
for the study.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
300 participants
