Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 97

Inclusion Criteria

-Systemic Sclerosis according to the American College of Rheumatology/The European League against Rheumatism (ACR/EULAR) 2013 criteria.
-Diffuse cutaneous form of SSc according to Leroy's criteria.
-Able and willing to sign the written informed consent form with comprehension of its contents and comply with the requirements of the
study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

Age<18yrs
Disease duration>36mths from time of 1nonRaynaud's phenomenon manifestation
mRSS<10 or>35 at screen and baseline visits
History of vasculitis,active or in remission
Diag connective tissue diseases(other than SSc)or PM/Scl
Pos HIV serology/known history of HIV active or in remission
Abnormal hepB and/or hepC tests indicative active/chronic infection:Abnormal HepB tests:Pos HBsAg OR pos total HBcAb with neg hepB surface Ab(HBsAb)/pos total hepB core antibody with pos HBsAb and presence of hepB DNA(HBV DNA)
Abnormal HepC tests:Pos antiHCV Ab and pos HCV RNA
Pos or 2confirmed indeterminate QTF tests at screen(regardless of prior treatment status)
Serious infection(eg pneumonia, pyelonephritis)within 4wk of screen,infection requiring hospitaliz/IV antibiotics within 4wk of screen or chronic bacterial infection(eg osteomyelitis)
History of anaphylaxis to any biologic therapy
Evidence of any clinically significant,severe/unstable,acute/chronically progressive,uncontrolled infection or medical condition(eg, cerebral,cardiac,pulmonary,renal,hepatic,gastrointestinal or neurologic other than SSc or SScILD)or previous,active/pending surgical disorder,or any condition that may affect pt safety in the judgment of the PI
At screen, the% predicted FVC <=75% AND%predicted DLCO after Hgb correction is<=40%
History of HF, LVEF <=45%, coronary artery disease,angina,myocardial infarction,ischemic/HCM
Any prior history of malignancy or active malignancy including lymphoproliferative diseases(except successfullytreated carcinoma insitu of the cervix,nonmetastatic squamous cell/basal cell carcinoma of the skin)within 5yrs prior to baseline
Ischemic ECG changes and/or other clinical significant ECG findings at screen
High dose steroids(>10mg/day prednisolone equiv)or change in steroid dose within 4wk prior to screen or during the screen period or expected changes during the study course
Previous treat with rituximab within 12mths prior to screen
Previous treat with bone marrow transplantation,tot lymphoid irradiation/ablative ultrahigh dose cyclophosphamide
Treat with high dose immunosuppressive drug(eg cyclophosphamide>1mg/kg oral/day or>750mg IV/mth;azathioprine>100mg/day;methotrexate>15mg/week;mycophenolate mofetil>2g/day)within 3mths of screen or change in dose within 4wk prior to baseline
Treat with etanercept,cyclosporine A,IVIG,rapamycin,Dpenicillamine,tyrosine K inhibitors within 4wk of screen or antithymocyte globulin within 6mths of screen
Treat with infliximab,certolizumab,golimumab,abatacept,or adalimumab,tocilizumab within 8wk of screen or anakinra within 1wk of screen
Treat with any IMP within 1mth of screen,or 5halflives,if known Abnormal lab tests at screen:
ALT or AST>2 times upper limit of ULN
Hgb<11 g/100mL(male) &<10 g/100mL(female)
Neutrophils<1500/mm^3(except<1000/mm3 for those of African descent)
PLT<100 000/mm^3
Creatinine=>150µmol/L
Lab parameters may be repeated once during the screen period if felt to be spurious or due to technical error in order to det eligibility
Current history of substance and/or alcohol abuse
Sanofi current employee/has an immediate family member(eg spouse,parents,child,sibling)Sanofi current employee
Currently incarcerated or anticipated/scheduled to be incarcerated during the course of the study
Any condition or circumstance that will preclude the pt from following and completing protocol requirements in the opinion of the PI
Pregnant or breastfeeding woman
Women who are of childbearing potential

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously on skin fibrosis in patients with dcSSc.;Secondary Objective: -To evaluate the efficacy of SAR156597 compared to placebo on<br>physical/functional disability in patients with dcSSc.<br>-To evaluate the efficacy of SAR156597 compared to placebo on<br>respiratory function in patients with dcSSc.<br>-To evaluate the safety profile of SAR156597 compared to placebo in<br>patients with dcSSc.<br>-To evaluate the potential for immunogenicity (anti-drug antibodies<br>[ADA] response) of SAR156597 in patients with dcSSc.<br>-To evaluate the pharmacokinetics (PK) (trough plasma concentrations)<br>of SAR156597<br>administered subcutaneously.;Primary end point(s): Change from baseline in mRSS;Timepoint(s) of evaluation of this end point: From Baseline to Week 24

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change from Baseline in Health Assessment Questionnaire Disability Index (HAD-QI), assessed with SHAQ<br><br>Change from baseline in respiratory function as measured by observed Forced Vital Capacity (FVC)<br>Change from baseline in observed Carbon Monoxide Diffusing Lung Capacity (DLco 8corrected for hemoglobin))<br>;Timepoint(s) of evaluation of this end point: From Baseline to Week 24

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