A Study of Telitacicept for the Treatment of Moderately to Severely Active Systemic Lupus Erythematosus (REMESLE-1)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of telitacicept in the treatment of moderately to severely active SLE.

Detailed Description
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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with heterogeneous manifestations and disease course. Despite advances in medical care, there are still significant unmet needs in SLE with diminished health-related quality of life (HRQoL), persistent disease activity, disease flares, intolerance to standard of care (SOC) therapies, and development of organ damage and co-morbidities. Telitacicept is a fully human TACI-Fc fusion protein that targets B lymphocyte stimulator (BLyS) and a proliferating-inducing ligand (APRIL).Blocking the interaction of BLyS and APRIL with their cell membrane receptors (TACI, BCMA, and BAFF-R) would inhibit B cell proliferation and maturation, suppresses immune responses, and may alleviate autoimmune symptoms. This Phase 3 study is a 2-stage operationally seamless study to evaluate the efficacy and safety of telitacicept 160 mg and 240 mg in a global patient population with active SLE disease. Stage 1 - a dose ranging study to evaluate the efficacy, safety, pharmacokinetics (PK) and PD of telitacicept 160 mg and 240 mg in an international cohort of adult SLE patients. Stage 2 - a confirmatory efficacy study to evaluate the telitacicept dose selected from Stage 1.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 2-Stage Trial to Evaluate Efficacy and Safety of Telitacicept Compared to Placebo in Patients With Moderately to Severely Active Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Telitacicept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has had a diagnosis of SLE for at least 6 months prior to the screening Visit. Moderate to severely active SLE is defined by the following: Hybrid SELENA SLEDAI (hSLEDAI) total score ≥ 6 at screening with clinical hSLEDAI score ≥ 4 points BILAG-2004 organ system scores of at least 1 A or 2 B at screening. Clinical hSLEDAI score of ≥ 4 at Day 0 prior to randomization At least one positive serologic parameter within the screening period Currently receiving at least one of the SOC SLE medications: oral corticosteroid, antimalarial and/or immunosuppressive agent. Other protocol defined inclusion criteria may apply. Exclusion Criteria: Active or unstable neuropsychiatric SLE or lupus nephritis Autoimmune or rheumatic disease other than SLE Significant, uncontrolled medical conditions not related to SLE Active and/or severe viral, bacterial or fungal infection History of malignancy within 5 years Other protocol defined exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept 160 mg<br>Telitacicept 160 mg + SOC | Drug: Telitacicept<br>* subcutaneous injection weekly for 52 weeks<br>* Other names: RC18;|
| Experimental: Telitacicept 240 mg<br>Telitacicept 240 mg + SOC | Drug: Telitacicept<br>* subcutaneous injection weekly for 52 weeks<br>* Other names: RC18;|
| Placebo Comparator: Placebo<br>Placebo + SOC | Drug: Placebo<br>* subcutaneous injection weekly for 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoint for Stage 1: SLE Responder Index (SRI-4) | Proportion of patients achieving a response in SRI-4 | Week 24 | 
| Primary Endpoint for Stage 2: SLE Responder Index (SRI-4) | Proportion of patients achieving a response in SRI-4 | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary endpoint for Stage 2: BILAG-based Combined Lupus Assessment (BICLA) | Proportion of patients achieving a response in BICLA | Week 52 | 
| Key secondary endpoint for Stage 2: achieve and sustain a low dose of corticosteroid | Proportion of patients who achieve or maintain prednisone </= 7.5 mg/d or equivalent | Weeks 40 - 52 | 
| Key secondary endpoint for Stage 2: Annualized severe flare rate | Severe flare according to the SLEDAI Flare Index (SFI) | Week 52 |