Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

• Register: EUCTR
• Last refreshed on: 15 October 2018
• Main ID: EUCTR2016-001028-80-DE
• Date of registration: 18/07/2016
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis
• Scientific title: Efficacy and safety of SAR156597 in the treatment of diffuse cutaneous Systemic Sclerosis (dcSSc): A randomized, double-blind, placebo-controlled, 24-week, proof of concept study
• Date of first enrolment: 08/11/2016
• Target sample size: 94
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001028-80
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Estonia, France, Germany, Italy, Mexico, Poland, Romania, Russian Federation, Ukraine, United Kingdom, United States

Contacts

• Affiliation: Sanofi-Aventis Deutschland GmbH

• Affiliation: Sanofi-Aventis Deutschland GmbH

Key inclusion & exclusion criteria

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:
-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 li

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic sclerosis
MedDRA version: 20.0 Level: LLT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 100000171021

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Code: SAR156597
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: SAR156597
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 100-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

Secondary Objective: -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.

Timepoint(s) of evaluation of this end point: From baseline to Week 24

Secondary Outcome(s)

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])

Timepoint(s) of evaluation of this end point: From baseline to Week 24

Secondary ID(s)

ACT14604

Source(s) of Monetary Support

sanofi-aventis recherche & développement