A Study to Evaluate the Efficacy and Safety of Abiprubart in Participants With Sjögren's Disease

Kiniksa Pharmaceuticals, GmbH

Status and phase: Enrolling; Phase 2

Conditions: Sjögrens Disease

Treatments: Drug: Placebo; Drug: Abiprubart

Study type: Interventional

Funder types: Industry

Identifiers

NCT06531395

KPL-404-C221

2024-512986-15-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

Primary objective of the study is to evaluate the effect of abiprubart on an established systemic disease activity measure for Sjögren's Disease.

Full description

This is a 56-week (24-week randomized double-blind period, 24-week active treatment period, and 8-week safety follow-up period) multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of abiprubart in participants with Sjögren's Disease with moderate or high systemic disease activity according to the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI). The objectives of the study are to evaluate efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of abiprubart compared with placebo across the estimated therapeutic range using different dosing regimens of abiprubart.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a diagnosis of Sjögren's Disease according to 2016 American College or Rheumatology (ACR)-EULAR Classification Criteria.
• Has ESSDAI value ≥ 5, counting only the biological, hematological, articular, cutaneous, glandular, lymphadenopathy, and constitutional organ domains at Screening.
• Is seropositive at Screening for anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA) antibodies tested at a central laboratory.
• Has stimulated whole salivary flow rate at Screening of ≥ 0.05 mL/min
• Weighs at least 40 kg and no more than 150 kg and has a body mass index (BMI) within the range of 18-40 kg/m2.

Exclusion criteria

• Prior exposure to any other anti-CD40/CD154 agent.
• Diagnosis of Sjögren's Disease overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness, including fibromyalgia with currently active, inadequately controlled symptoms.
• Has received cataract surgery, Lasik, or other ophthalmologic surgery procedure (e.g., lachrymal plug) in the 6 months prior to Screening.
• Injectable corticosteroids (including intra-articular) within 8 weeks prior to randomization.
• Has started, stopped or adjusted dose/regimen of medications for treatment of, or known to cause dry mouth/eyes within the 30 days prior to screening or is anticipating change to these treatment regimens during the study.
• Has history of immunodeficiency (e.g., immune disorders or disorders that result in decreased immunity), including human immunodeficiency virus (HIV).
• History of thromboembolic event or a significant risk of future thromboembolic events.
• Has a known high risk of infection; Has a history of chronic or recurrent infectious disease; Has any known or suspected active infection, or has had a serious infection requiring hospitalization, or has been treated with IV/IM antibiotics for an infection within 8 weeks prior to first dose of study drug or treatment with oral antibiotics for an infection within 2 weeks prior to first dose of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 3 patient groups, including a placebo group

Abiprubart 400mg SC q2wk

Experimental group

Description:

Part A: Loading dose of abiprubart 800 mg subcutaneous (SC) followed by abiprubart 400 mg SC every 2 weeks (q2wk) through Week 22. Part B: Abiprubart 400 mg SC q2wk: abiprubart 400 mg SC q2wk up to and including Week 46.

Treatment:

Drug: Abiprubart

Abiprubart 400mg SC q4wk

Experimental group

Description:

Part A: Loading dose of abiprubart 800 mg SC followed by abiprubart 400 mg SC q2wk through Week 22 which will alternately administer placebo or abiprubart to provide active drug every 4 weeks (q4wk) while maintaining treatment concealment. Part B: Abiprubart 400 mg SC q4wk: abiprubart 400 mg SC q2wk up to and including Week 46 which will alternately administer placebo or abiprubart to provide active drug q4wk while maintaining treatment concealment.

Treatment:

Drug: Abiprubart

Drug: Placebo

Placebo

Placebo Comparator group

Description:

Part A: A matched volume placebo loading dose followed by placebo SC injections q2wk through Week 22. Part B: Participants assigned to placebo in Part A will transition to active abiprubart treatment, according to randomized assignment, with either abiprubart 400 mg SC q2wk or abiprubart 400 mg SC q4wk.

Treatment:

Drug: Abiprubart

Drug: Placebo