Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 94

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 <18 years of age.
-Disease duration of >36 months from time of first non-Raynaud’s phenomenon manifestation.
-mRSS <10 or >35 at screening and baseline visits.
-History of vasculitis, active or in remission
-Diagnosis of connective tissue disease (other than SSc) or overlap syndrome (eg, polymyositis/SSc).
-Positive Human Immunodeficiency Virus (HIV) serology or a known history of HIV infection, active or in remission
-Abnormal hepatitis B and/or hepatitis C tests indicative of active or chronic infection ((refer to protocol)
-Positive or 2 confirmed indeterminate Quantiferon-TB Gold tests at screening
-Serious infection (eg, pneumonia, pyelonephritis) within 4 weeks of screening, infection requiring hospitalization or intravenous antibiotics within 4 weeks of screening or chronic bacterial infection (eg, osteomyelitis).
-History of anaphylaxis to any biologic therapy.
-Evidence of any clinically significant, severe or unstable, acute or chronically progressive, uncontrolled infection or medical condition (eg, cerebral, cardiac, pulmonary, renal, hepatic, gastrointestinal or neurologic other than SSc or SSc-ILD) or previous, active or pending surgical disorder, or any condition that may affect patient safety in the judgment of the Investigator.
-At screening, the % predicted forced vital capacity (FVC) is =75% AND % predicted carbon monoxid diffusing lung capacity (DLCO) after hemoglobin correction is =40%
-History of heart failure (including acutely decompensated in the setting of preserved ejection fraction), Left Ventricular Ejection Fraction (LVEF) =45%, coronary artery disease, angina, myocardial infarction, ischemic cardiomyopathy and/or hypertrophic cardiomyopathy
-Any prior history of malignancy or active malignancy, including lymphoproliferative diseases (except successfully-treated carcinoma in-situ of the cervix, non-metastatic squamous cell or basal cell carcinoma of the skin) within 5 years prior to baseline.
Ischemic ECG changes (except those NOT supported by the findings of a left heart catheterization performed in the last year within screening) and/or other clinically significant ECG findings (Appendix L) at screening. (All abnormal ECG finding will be reviewed and confirmed by a local cardiologist.)
-High dose steroids (>10 mg/day prednisolone equivalent); or change in steroid dose within 4 weeks prior to screening or during the screening period; or expected changes during the course of the study.
-Previous treatment with rituximab within 12 months prior to screening.
-Previous treatment with bone marrow transplantation, total lymphoid irradiation or ablative ultrahigh dose cyclophosphamide.
-Treatment with high dose immunosuppressive drug (eg, cyclophosphamide >1 mg/kg oral/day or >750 mg IV/month; azathioprine >100 mg/day; methotrexate >15 mg/week; mycophenolate mofetil >2 g/day) within 3 months of screening or change in dose within 4 weeks prior to baseline.
-Treatment with etanercept, cyclosporine A, intravenous immunoglobulin (IVIG), rapamycin, Dpenicillamine, tyrosine kinase inhibitors within 4 weeks of screening or antithymocyte globulin within 6 months of screening.

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

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): - Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), assessed with SHAQ<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 [corrected for hemoglobin])<br> ;Timepoint(s) of evaluation of this end point: From baseline to Week 24

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