Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis
Condition: Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: SAR156597; Placebo
Intervention description: Pharmaceutical form: Solution Route of administration: Subcutaneous; Pharmaceutical form: Solution Route of administration: Subcutaneous
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate, in comparison with placebo, the efficacy of SAR156597 administered
      subcutaneously for 24 weeks on skin fibrosis in participants with diffuse cutaneous systemic
      sclerosis (dcSSc).

      Secondary Objectives:

        -  To evaluate the efficacy of SAR156597 compared to placebo on physical/functional
           disability in participants with dcSSc.

        -  To evaluate the efficacy of SAR156597 compared to placebo on respiratory function of
           participants with dcSSc.

        -  To evaluate the safety profile of SAR156597 compared to placebo in participants with
           dcSSc.

        -  To evaluate the potential for immunogenicity (anti-drug antibodies response) of
           SAR156597 in participants with dcSSc.

        -  To evaluate the pharmacokinetics (trough plasma concentrations) of SAR156597
           administered subcutaneously for 24 weeks.
    

Eligibility criteria:

        Inclusion criteria :

          -  Systemic Sclerosis (SSc) according to the American College of Rheumatology/The
             European League against Rheumatism (ACR/EULAR) 2013 criteria.

          -  Diffused 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 complied with the requirements of the study protocol.

        Exclusion criteria:

          -  Aged less than (<) 18 years of age.

          -  Disease duration for greater than (>) 36 months from time of first non-Raynaud's
             phenomenon manifestation.

          -  Modified Rodnan Skin Score <10 or >35 at screening and baseline visits.

          -  History of vasculitis, active or in remission.

          -  Diagnosis of connective tissue diseases (other than SSc) or overlap syndrome (eg,
             polymyositis/scleroderma).

          -  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:

          -  Abnormal Hepatitis B tests: Positive hepatitis B surface antigen (HBsAg) OR positive
             total hepatitis B core antibody (HBcAb) with negative hepatitis B surface antibody
             (HBsAb) OR positive total HBcAb with positive HBsAb and presence of hepatitis B virus
             deoxyribonucleic acid.

          -  Abnormal Hepatitis C tests: Positive anti-hepatitis C virus antibody (HCV Ab) and
             positive HCV ribonucleic acid.

          -  Positive or 2 confirmed indeterminate Quantiferon-tuberculosis Gold tests at screening
             (regardless of prior treatment status).

          -  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-interstitial lung disease) or previous, active or pending surgical disorder, or
             any condition that may affect participant safety in the judgment of the Investigator.

          -  At screening, the percent (%) predicted forced vital capacity was less than or equal
             to (<=75) % and % predicted carbon monoxide diffusing lung capacity after hemoglobin
             correction is <=40%.

          -  History of heart failure (including acutely decompensated in the setting of preserved
             ejection fraction), left ventricular ejection fraction <= 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 carcinoma or basal cell carcinoma of the skin) within 5 years prior to
             baseline.

          -  Ischemic electrocardiogram (ECG) changes (except those not supported by the findings
             of a left heart catheterization performed in the last year) and/or other clinically
             significant ECG findings. (All abnormal ECG finding were 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 randomization (or baseline visit); 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 ultra-high dose cyclophosphamide.

          -  Treatment with high dose immunosuppressive drug (eg, cyclophosphamide >1 mg/kilogram
             (kg) oral/day or >750 mg intravenous (IV)/month; azathioprine >100 mg/day;
             methotrexate >15 mg/week; mycophenolate mofetil >2 gram (g)/day) within 3 months of
             screening or change in dose within 4 weeks prior to randomization (or baseline visit);
             or expected changes in dose during the course of the study.

          -  Treatment with etanercept, cyclosporine A, IV immunoglobulin, rapamycin,
             D-penicillamine, tyrosine kinase inhibitors within 4 weeks of screening or
             antithymocyte globulin within 6 months of screening.

          -  Treatment with infliximab, certolizumab, golimumab, abatacept, or adalimumab,
             tocilizumab within 8 weeks of screening or anakinra within 1 week of screening.

          -  Treatment with any investigational drug within 1 month of screening, or 5 half-lives,
             if known (whichever was longer).

          -  Abnormal laboratory tests at screening:

          -  Alanine transaminase or aspartate transaminase >2 times upper limit of normal range;

          -  Hemoglobin <11 g/100 milliliter (mL) for male and <10 g/100 mL for female;

          -  Neutrophils <1500/mm^3 (except <1000/mm^3 for those of African descent);

          -  Platelets <100 000/mm^3;

          -  Creatinine greater than or equal to (>=)150 micromole/Liter (mcgmol/L).

          -  Current history of substance and/or alcohol abuse.

          -  Any condition or circumstance that would preclude the participant from following and
             completing protocol requirements, in the opinion of the Investigator.

          -  Pregnant or breastfeeding woman.

          -  Women who were of childbearing potential not protected by highly-effective
             contraceptive method(s) of birth control, and/or who were unwilling or unable to be
             tested for pregnancy.

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.