Clinical trial NCT01651143: Proof of Biological Activity of SAR100842 in Systemic Sclerosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-07-26
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Safety and tolerability during the 8 week treatment period (core part): Number of patients reporting adverse events
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Change from baseline to Week 8 in biomarkers obtained from blood and skin
timeFrame: Day 1 and Week 8 (core part)
measure: Change from baseline to Week 8 in Modified Rodnan Skin Score (mRSS)
timeFrame: Day 1 and Week 8 (core part)
measure: Change from baseline to Week 8 in Scleroderma Health Assessment Questionnaire (SHAQ) score
timeFrame: Day 1 and Week 8 (core part)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Investigational Site Number 840006
state: Arizona
city: Washington
country: United States
facility: Investigational Site Number 840003
state: District of Columbia
city: Baltimore
country: United States
facility: Investigational Site Number 840004
state: Maryland
city: Boston
country: United States
facility: Investigational Site Number 840001
state: Massachusetts
city: Ann Arbor
country: United States
facility: Investigational Site Number 840002
state: Michigan
city: New Brunswick
country: United States
facility: Investigational Site Number 840007
state: New Jersey
city: Pittsburgh
country: United States
facility: Investigational Site Number 840008
state: Pennsylvania
city: Lille
country: France
facility: Investigational Site Number 250003
city: Paris Cedex 14
country: France
facility: Investigational Site Number 250001
city: Milano
country: Italy
facility: Investigational Site Number 380001
city: Zürich
country: Switzerland
facility: Investigational Site Number 756001
city: London
country: United Kingdom
facility: Investigational Site Number 826001
city: Salford
country: United Kingdom
facility: Investigational Site Number 826002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.