E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 100000171021 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously on skin fibrosis in patients with dcSSc. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of SAR156597 compared to placebo on physical/functional disability in patients with dcSSc.
-To evaluate the efficacy of SAR156597 compared to placebo on respiratory function in patients with dcSSc.
-To evaluate the safety profile of SAR156597 compared to placebo in patients with dcSSc.
-To evaluate the potential for immunogenicity (anti-drug antibodies [ADA] response) of SAR156597 in patients with dcSSc.
-To evaluate the pharmacokinetics (PK) (trough plasma concentrations) of SAR156597
administered subcutaneously. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal exclusion criteria |
-Aged <18 years.
-Disease duration for >36 months from time of first non-Raynaud’s phenomenon manifestation.
-Modified Rodnan Skin Score (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,
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 hepatitis B core antibody with positive HBsAb and presence of hepatitis B DNA (HBV DNA).
-Abnormal Hepatitis C tests: Positive anti-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-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 FVC is ≤75% AND % predicted DLCO
after hemoglobin correction is ≤40%
-History of heart failure, LVEF ≤ 45%, coronary artery disease, angina,
myocardial infarction, ischemic/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 and/or other clinically significant ECG findings at screening.
-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.
-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
-Abnormal laboratory tests at screening:
-ALT or AST >2 times upper limit of normal range (ULN);
-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 ≥150 μmol/L.
Note: Laboratory parameters may be repeated once during the screening period if felt to be spurious or due to technical error in order to determine eligibility.
-Current history of substance and/or alcohol abuse
-Current employee of Sanofi or has an immediate family member (eg, spouse, parents, child or sibling) who is a current employee of Sanofi.
-Currently incarcerated or anticipated/scheduled to be incarcerated during the course of the study.
-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 G for United Kingdom), and/or who are unwilling or unable to be tested for pregnancy.
Note: Women of childbearing potential must have a confirmed negative pregnancy test at screening and randomization visits. They must use an effective contraceptive method throughout the entire duration of the study treatment, and for at least 12 weeks after the last administration of IMP.
Postmenopausal women must be amenorrheic for at least 12 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in mRSS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), assessed with SHAQ
- Change from baseline in respiratory function as measured by observed Forced Vital Capacity (FVC)
Change from baseline in observed Carbon Monoxide Diffusing Lung Capacity (DLco [corrected for hemoglobin]) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Austria |
Belgium |
Estonia |
France |
Germany |
Italy |
Mexico |
Poland |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |