Proof of Biological Activity of SAR100842 in Systemic Sclerosis

• ClinicalTrials.gov Identifier: NCT01651143
• Recruitment Status: Completed
• First Posted: July 26, 2012
• Last Update Posted: March 25, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Systemic Sclerosis	Drug: SAR100842; Drug: Placebo (for SAR100842)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: January 2013
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: April 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability during the 8 week treatment period (core part): Number of patients reporting adverse events [ Time Frame: Up to 8 weeks ]

Secondary Outcome Measures :

1. Change from baseline to Week 8 in biomarkers obtained from blood and skin [ Time Frame: Day 1 and Week 8 (core part) ]
2. Change from baseline to Week 8 in Modified Rodnan Skin Score (mRSS) [ Time Frame: Day 1 and Week 8 (core part) ]
3. Change from baseline to Week 8 in Scleroderma Health Assessment Questionnaire (SHAQ) score [ Time Frame: Day 1 and Week 8 (core part) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Investigational Site Number 840006

Scottsdale, Arizona, United States, 85259-5499

United States, District of Columbia

Investigational Site Number 840003

Washington, District of Columbia, United States, 20007

United States, Maryland

Investigational Site Number 840004

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Investigational Site Number 840001

Boston, Massachusetts, United States, 02118

United States, Michigan

Investigational Site Number 840002

Ann Arbor, Michigan, United States, 48106

United States, New Jersey

Investigational Site Number 840007

New Brunswick, New Jersey, United States, 08903

United States, Pennsylvania

Investigational Site Number 840008

Pittsburgh, Pennsylvania, United States, 15213

France

Investigational Site Number 250003

Lille, France, 59037

Investigational Site Number 250001

Paris Cedex 14, France, 75679

Italy

Investigational Site Number 380001

Milano, Italy, 20122

Switzerland

Investigational Site Number 756001

Zürich, Switzerland, 8091

United Kingdom

Investigational Site Number 826001

London, United Kingdom

Investigational Site Number 826002

Salford, United Kingdom, M6 8HD

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT01651143
• Other Study ID Numbers: ACT12339; 2012-001369-34 ( EudraCT Number ); U1111-1127-2854 ( Other Identifier: UTN )
• First Posted: July 26, 2012
• Last Update Posted: March 25, 2016
• Last Verified: February 2016

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases