Clinical Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of ACT-334441 in Subjects With Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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International trial to evaluate the biological activity and safety of cenerimod (ACT-334441) in systemic lupus erythematosus (SLE) patients.

Detailed Description
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This multicentre, double-blind, placebo-controlled study will have a staggered approach (Part A and B). In part A, eligible patients will be randomly assigned (1:1:1:1) to once daily oral administration of cenerimod (0.5, 1, 2 mg) or placebo. After all patients have completed 4 weeks of treatment during part A, an Independent Data Monitoring Committee will review non-blinded data in an interim analysis to evaluate the safety profile of cenerimod and recommend whether the study could proceed to part B. In part B, additional patients will be randomized (3:1) to once daily oral administration of cenerimod 4 mg or placebo. All participants will receive study medication for 12 weeks.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-response Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of ACT-334441 in Subjects With Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Matching placebo
* Drug: Cenerimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants aged 18 to 65 years with established SLE. Participants must have active SLE, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of at least 2 points for musculoskeletal or mucocutaneous manifestations and history or presence at screening of positive anti-nuclear antibodies (ANA) or anti-double-stranded DNA (anti-dsDNA) antibodies. Enrolled participants must be treated with background SLE medications. Exclusion Criteria: Participants with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic, ophthalmological, infection and infection risks, history or presence of malignancy, history or presence of bone marrow or solid organ transplantation) or lactating or pregnant women. Participants with severe SLE disease or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Cenerimod 0.5 mg (Part A)<br>Participants will receive cenerimod 0.5 mg capsules orally once daily for 12 weeks. | Drug: Cenerimod<br>* One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).<br>* Other names: ACT-334441;|
| Experimental: Cenerimod 1 mg (Part A)<br>Participants will receive cenerimod 1 mg capsules orally once daily for 12 weeks. | Drug: Cenerimod<br>* One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).<br>* Other names: ACT-334441;|
| Experimental: Cenerimod 2 mg (Part A)<br>Participants will receive cenerimod 2 mg capsules orally once daily for 12 weeks. | Drug: Cenerimod<br>* One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).<br>* Other names: ACT-334441;|
| Experimental: Cenerimod 4 mg (Part B)<br>Participants will received cenerimod 4 mg capsules orally once daily for 12 weeks. This treatment arm will start after all patients in Part A have completed 4 weeks of placebo, 0.5 mg, 1 mg and 2 mg cenerimod treatment. | Drug: Cenerimod<br>* One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).<br>* Other names: ACT-334441;|
| Placebo Comparator: Matching placebo (Part A and B)<br>Capsules of matching placebo taken orally once daily for 12 weeks. | Drug: Matching placebo<br>* One capsule of cenerimod to be taken once daily, irrespective of food intake. The capsule is to be swallowed whole. The capsule should be taken each day at approximately the same time (preferably each morning).<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT) | The primary objective of the clinical study was to asses whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12. | Baseline to end-of-treatment (EOT) (up to 12 weeks) | 
| Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment | The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at visit minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12. | Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment Visit (up to 12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic lupus erythematosus