Proof of Biological Activity of SAR100842 in Systemic Sclerosis

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

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.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: SAR100842; Drug: Placebo (for SAR100842)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Investigational Site Number 250003
  • Paris Cedex 14, France, 75679
    • Investigational Site Number 250001
• Italy
  • Milano, Italy, 20122
    • Investigational Site Number 380001
• Switzerland
  • Zürich, Switzerland, 8091
    • Investigational Site Number 756001
• United Kingdom
  • London, United Kingdom
    • Investigational Site Number 826001
  • Salford, United Kingdom, M6 8HD
    • Investigational Site Number 826002
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Investigational Site Number 840006
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Investigational Site Number 840003
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Investigational Site Number 840004
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Investigational Site Number 840001
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Investigational Site Number 840002
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Investigational Site Number 840007
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Investigational Site Number 840008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Patients with high dose or unstable low dose immunosuppressive drugs, cytotoxic, anti-fibrotic or glucocorticoids drugs at least 4 weeks prior to screening
2. Serum creatinine > 2.0 mg/dL
3. Gastrointestinal involvement preventing oral administration of study drug
4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SAR100842; 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; Pharmaceutical form: tablets Route of administration: oral
PLACEBO_COMPARATOR: Placebo; 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; Pharmaceutical form: tablets Route of administration: oral; Drug: Placebo (for SAR100842); Pharmaceutical form: tablets Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Allanore Y, Distler O, Jagerschmidt A, Illiano S, Ledein L, Boitier E, Agueusop I, Denton CP, Khanna D. Lysophosphatidic Acid Receptor 1 Antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis: A Double-Blind, Randomized, Eight-Week Placebo-Controlled Study Followed by a Sixteen-Week Open-Label Extension Study. Arthritis Rheumatol. 2018 Oct;70(10):1634-1643. doi: 10.1002/art.40547. Epub 2017 Nov 6.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): April 1, 2014

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 24, 2012
• First Posted (ESTIMATE): July 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 25, 2016
• Last Update Submitted That Met QC Criteria: February 26, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: ACT12339; 2012-001369-34 (EUDRACT_NUMBER); U1111-1127-2854 (OTHER: UTN)