Efficacy and Safety of Afimetoran compared with Placebo in Participants with Active Systemic Lupus Erythematosus

Phase 2

Conditions: Health Condition 1: M329- Systemic lupus erythematosus, unspecified

Registration Number: CTRI/2024/01/061756

Lead Sponsor: BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Yet Recruiting

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1.Diagnosed = 12 weeks before the screening visit and qualify as having SLE, according to the SLE International Collaborating Clinics (SLICC) Classification Criteria at the screening visit

2.Test positive for at least 1 of the following lupus-related autoantibodies as determined by the central lab at the time of screening: antinuclear antibody (ANA) = 1:80, anti–double-stranded deoxyribonucleic acid (dsDNA) antibody, or anti-Smith (Sm) antibody

3.Total hybrid (h)SLEDAI score = 6 points and clinical hSLEDAI score = 4 points with joint involvement and/or rash (score must be confirmed by the lupus expert review panel [LERP])

i.Alopecia and mucosal ulcers do not count toward the points required for eligibility at screening. Active neuropsychiatric SLE is exclusionary for study participation. Thus, points for seizures, psychosis, organic brain syndrome, visual disturbance, cranial neuropathy, lupus headache, and cerebrovascular accident, as defined by the Hybrid SLEDAI, will also not contribute to scoring

ii.Clinical hSLEDAI excludes laboratory abnormalities such as hematuria, pyuria, urinary casts, proteinuria, positive anti-dsDNA, decreased complement, thrombocytopenia, and leukopenia

4.At least 1 of the following BILAG-based protocol-specific manifestations of SLE (must be confirmed by the LERP):

i.BILAG-2004 A or B grade in the Mucocutaneous body system. If a BILAG B grade for Mucocutaneous disease is due to BILAG #6 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-2004 A or B score in the Musculoskeletal body system due to active polyarthritis (see protocol section 6.1 for criteria)

5.Have a PGA score of disease activity on a 0-3 VAS = 1

6.Be using at least 1 background SLE treatment prior to screening, at a stable dose that must be maintained through study completion.

i.Qualifying background treatments include the following: oral systemic corticosteroids (CS); azathioprine; 6-mercaptopurine (6-MP); methotrexate (MTX); leflunomide; MMF; tacrolimus and antimalarials (e.g., chloroquine, hydroxychloroquine, or quinacrine)

ii.Background SLE treatment use is permitted according to specific protocol limits, including maximal dose and minimum duration at stable dose prior to randomization.

iii.Daily CS dose may not exceed 20 mg per day of prednisone or equivalent

iv.For participants whose only background SLE therapy is CS, the dose should be = 10 mg prednisone or equivalent daily.

i)Changes to CS doses are allowed as described in Section 7.7.2.1.

v.If CS are being used (with or without a non-CS SLE treatment), they must be in use for at least 4 weeks and at a stable dose for at least 2 weeks prior to screening.

vi.Background non-CS SLE treatments must be in use for at least 8 weeks and at a stable dose for at least 4 weeks prior to screening.

vii.Required discontinuation periods for other immunomodulatory drugs or biologic drugs are provided in APPENDIX 18 of the protocol. 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.

Inclusion Criteria for LTE

1)Signed Written Informed Consent

i.Participants must have signed and dated a

Exclusion Criteria

1.Participants with active severe lupus nephritis (LN) as assessed by the investigator.

2.Active or unstable neuropsychiatric lupus manifestations defined by the Hybrid SLEDAI.

i. Additionally, participants with active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG-2004 A criteria, are excluded, with the exception of participants with mononeuritis multiplex and polyneuropathy, who are allowed.

3.Diagnosis of Mixed Connective Tissue Disease for which the predominant diagnosis is not SLE.

i. For example, participants whose prevailing signs and symptoms are consistent with dermatomyositis or systemic sclerosis should be excluded. Alternatively, participants who meet classification criteria for SLE and are treated predominantly as SLE patients, but also have erosive arthritis (i.e., Rhupus), thyroiditis, antiphospholipid syndrome, or polymyositis, should not be systematically excluded. The investigator should consider consultation with the MM to ensure such cases are appropriate for study inclusion.

4.Antiphospholipid Syndrome (APS):

i.The following are exclusionary:

i)Confirmed diagnosis of APS as defined by the revised Sapporo criteria (see APPENDIX 19) if there has been a thrombotic event or pregnancy morbidity within 12 months before screening

ii)History of probable or definite catastrophic APS

ii.The following are not exclusionary:

i)A positive result for antiphospholipid antibodies at screening is not exclusionary provided there is no history of thrombosis or pregnancy mortality in the past 12 months

ii)A thrombotic event more than 12 months before screening is not exclusionary provided the subject is maintained on appropriate anticoagulation therapy (warfarin, low-molecular weight heparin, or newer anticoagulants

iii)A history of APS with a history of pregnancy morbidity more than 12 months before screening is not exclusionary provided the subject is maintained on low-dose aspirin or equivalent

5.Inability to comply with restrictions and prohibited treatments, as listed in Section 7.7: Concomitant Therapy.

6.Current daily Oral CS (prednisone or equivalent) = 20 mg QD. Prednisone equivalents are provided. Further specifications are as follows:

7.Intramuscular, intra-articular, intrabursal, and intravenous (IV) CS use is prohibited within 8 weeks before screening.

8.Inhaled and intranasal CS for nonlupus conditions are permitted and will not count toward the maximum CS dose allowed.

i.Modified-release CS formulations are prohibited.

9.Changes in oral CS dose from 2 weeks prior to screening through initial study drug dosing

10.Current or recent use of biologic agent or other prohibited immunosuppressive medication defined

11.Taking more than 1 immunosuppressant, not including CS or antimalarial drugs.

12.Prior exposure to BMS-986256 or another combined TLR7/8 antagonist

13.Use of topical medications/treatments that could affect the appearance of skin lesions within 2 weeks prior to screening

14.Use of strong CYP3A4 inhibitors

15.Recent exposure to other investigational agents; investigational agents must be discontinued at least 4 weeks or 5 half-lives before screening, whichever is longer.

16.Use of any Chinese traditional medicine intended for use in SLE within 4 w