Study Evaluating ALX-0061 Administered Subcutaneously in Patients with Systemic Lupus Erythematosus

Phase 1

Conditions: MedDRA version: 18.0Level: LLTClassification code 10025139Term: Lupus erythematosus systemicSystem Organ Class: 100000004859
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Moderate to Severe Active Systemic Lupus Erythematosus

Registration Number: EUCTR2015-000372-95-ES

Lead Sponsor: Ablynx N.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

Inclusion Criteria

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 ACR (see Appendix 9.1) 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 SLEDAI 2K score >=6 at screening.
4. Have at least one A or one B score on the revised BILAG 2004 criteria for the mucocutaneous and/or musculoskeletal system.
5. Have seropositive disease at screening for 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 aga

Exclusion Criteria

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 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 successfully-treated 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 JAK inhibitors at any time.
20. Abnormality in screening laboratory test results:
a. ALT and/or 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 [Appendix 9.4]).
h. Any other clinically significant abnormal screening laboratory results as evaluated by the Invest

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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 Objective: 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.;Primary end point(s): The percentage of subjects who achieved a response at Week 24 according to the composite mBICLA (BILAG-based Combined Lupus Assessment) score.;Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome Measures

Name	Time	Method

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