Proof of Biological Activity of SAR100842 in Systemic Sclerosis

Study Overview
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Brief Summary
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Primary Objective: - To evaluate safety and tolerability of 8-week oral administration of SAR100842 in patients with diffuse cutaneous systemic sclerosis. Secondary Objectives: To evaluate the pharmacodynamic effect of SAR100842 in patients with systemic sclerosis as measured by disease related biomarkers and Lysophosphatidic acid (LPA) receptor signaling markers in blood and skin; To explore the effect of SAR100842 on skin thickness in patients with systemic sclerosis as measured by the modified Rodnan Skin Score (mRSS); To explore the effect of SAR100842 on quality of life as measured by the Scleroderma Modified Health Assessment Questionnaire (SHAQ); To document long term safety of SAR100842 during the extension part.

Detailed Description
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Core part: randomized, double-blind, placebo-controlled study - 8-week treatment Extension part for participants completing the core part: Open label non-controlled study - 16-week treatment Each patient's participation in the study will be approximately 13 or 33 weeks depending on their participation in the extension part: up to 2 weeks of screening, 8 weeks of treatment in the core part, 1 to 30 days wash-out between core part and extension part , 16 weeks of treatment in the extension part and 3 weeks of follow up.

Official Title
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Double-blind, Randomized, 8-week Placebo-controlled, and 16-week Open-label Extension Study Investigating the Safety, Pharmacokinetics and Pharmacodynamics of SAR100842 Given Orally to Patients With Diffuse Cutaneous Systemic Sclerosis

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Drug: SAR100842
* Drug: Placebo (for SAR100842)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : - Patients who meet the American College of Rheumatology (ACR) criteria for systemic sclerosis with diffuse cutaneous involvement and <36 months since the onset of the first systemic sclerosis manifestation other than Raynaud's phenomenon and have a Modified Rodnan Skin Score (mRSS) ≥ 15 and an area of definite involvement of the dorsal forearm that is considered amenable to repeated 4mm skin biopsies. Exclusion criteria: Patients with high dose or unstable low dose immunosuppressive drugs, cytotoxic, anti-fibrotic or glucocorticoids drugs at least 4 weeks prior to screening Serum creatinine > 2.0 mg/dL Gastrointestinal involvement preventing oral administration of study drug Severe cardiac and/or pulmonary disease The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: SAR100842<br>Core part: SAR100842 300 mg, oral administration twice daily, for 8 weeks Extension part: SAR100842 300 mg, oral administration twice daily, for 16 additional weeks | Drug: SAR100842<br>* Pharmaceutical form: tablets Route of administration: oral<br>|
| Placebo Comparator: Placebo<br>Core part: Placebo (for SAR100842), oral administration twice daily, for 8 weeks Extension part: SAR100842 300 mg, oral administration twice daily, for 16 additional weeks | Drug: SAR100842<br>* Pharmaceutical form: tablets Route of administration: oral<br>Drug: Placebo (for SAR100842)<br>* Pharmaceutical form: tablets Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability during the 8 week treatment period (core part): Number of patients reporting adverse events |  | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 8 in biomarkers obtained from blood and skin |  | Day 1 and Week 8 (core part) | 
| Change from baseline to Week 8 in Modified Rodnan Skin Score (mRSS) |  | Day 1 and Week 8 (core part) | 
| Change from baseline to Week 8 in Scleroderma Health Assessment Questionnaire (SHAQ) score |  | Day 1 and Week 8 (core part) |