Inclusion criteria :|
- Systemic Sclerosis (SSc) 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.
- Age <18 years of age.
- Disease duration for >36 months from time of first non-Raynaud's phenomenon
- MRSS <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,
- Positive 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
- 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 DNA
- Abnormal Hepatitis C tests: Positive anti-hepatitis C virus antibody (HCV Ab) and
positive HCV RNA.
- Positive or 2 confirmed indeterminate Quantiferon-TB 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 patient safety in the judgment of the Investigator.
- At screening, the % predicted forced vital capacity (FVC) is â‰¤75% AND % predicted
carbon monoxide diffusing lung capacity (DLCO) after hemoglobin correction is â‰¤40%
- History of heart failure (including acutely decompensated in the setting of preserved
ejection fraction), left ventricular ejection fraction â‰¤ 45%, coronary artery disease,
angina, myocardial infarction, ischemic cardiomyopathy and/or hypertrophic
- 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
- Ischemic 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 will be reviewed and confirmed by a local
- High dose steroids (>10 mg/day prednisolone equivalent); or change in steroid dose
within 4 weeks prior to/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 ultra-high 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, 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 is longer).
- Abnormal laboratory tests at screening:
- Alanine transaminase or aspartate transaminase >2 times upper limit of normal range;
- Hemoglobin <11 g/100 mL for male and <10 g/100 mL for female;
- Neutrophils <1500/mm^3 (except <1000/mm3 for those of African descent);
- Platelets <100 000/mm^3;
- Creatinine â‰¥150 Âµmol/L.
- Current history of substance and/or alcohol abuse
- Any condition or circumstance that will preclude the patient from following and
completing protocol requirements, in the opinion of the Investigator.
- Pregnant or breastfeeding woman
- Women who are of childbearing potential not protected by highly-effective
contraceptive method(s) of birth control as (defined in the informed consent form
and/or Appendix A for United Kingdom), and/or who are unwilling or unable to be tested
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.