Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

ID: NCT02921971
Status: Recruiting
Phase: Phase 2
Start Date: November 01, 2016
First Submitted: September 30, 2016
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Sanofi
Location: Argentina, Austria, Belgium, Estonia, France, Germany, Italy, Mexico, Poland, Romania, Russian Federation, Ukraine, United Kingdom, United States
Conditions: Systemic Sclerosis
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Study Description

Brief Summary

Primary Objective:

To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously for 24 weeks on skin fibrosis in patients with dcSSc.

Secondary Objectives:

- 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 for 24 weeks.

Detailed Description

The total study duration per patient will be 39 weeks; consisting of a 4-week screening, a 24-week of study treatment period, and a 11-week follow-up with no study drug treatment.
Condition or disease Intervention/treatment Phase

Systemic Sclerosis

Drug: SAR156597 (ACT14604)
Other Names
Drug: Placebo
Other Names
Phase 2

Tracking Information

First Submitted DateSeptember 30, 2016
Last Update Posted DateFebruary 22, 2018
Start DateNovember 01, 2016
Anticipated Completion DateJanuary 01, 2019
Primary Completion DateOctober 01, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change from baseline in mRSS [Time Frame: From baseline to Week 24]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), assessed with SHAQ [Time Frame: From baseline to Week 24]

  • Change from baseline in respiratory function as measured by observed Forced Vital Capacity (FVC) [Time Frame: From baseline to Week 24]

  • Change from baseline in observed Carbon Monoxide Diffusing Lung Capacity (DLco [corrected for hemoglobin]) [Time Frame: From baseline to Week 24]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleEffectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis
Official TitleEfficacy 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
Brief Summary

Primary Objective:

To evaluate, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously for 24 weeks on skin fibrosis in patients with dcSSc.

Secondary Objectives:

- 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 for 24 weeks.

Detailed Description

The total study duration per patient will be 39 weeks; consisting of a 4-week screening, a 24-week of study treatment period, and a 11-week follow-up with no study drug treatment.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
94
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Systemic Sclerosis
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: SAR156597 (ACT14604)

Pharmaceutical form:Solution Route of administration: Subcutaneous

Other Names
Drug: Placebo

Pharmaceutical form:Solution Route of administration: Subcutaneous

Other Names
Study Groups/Cohorts
SAR156597
SAR156597 will be given on a specific time period

Placebo
Placebo will be given on a specific time period

Study Arms
Placebo Comparator Placebo
Placebo will be given on a specific time period
Drug : Placebo
Pharmaceutical form:Solution Route of administration: Subcutaneous

Experimental SAR156597
SAR156597 will be given on a specific time period
Drug : SAR156597 (ACT14604)
Pharmaceutical form:Solution Route of administration: Subcutaneous

Arm Intervention/Treatment
Placebo Comparator Placebo
Placebo will be given on a specific time period
Drug : Placebo
Experimental SAR156597
SAR156597 will be given on a specific time period
Drug : SAR156597 (ACT14604)

Recruitment Information

Recruitment Status:Recruiting
Enrollment94
Completion DateJanuary 01, 2019
Eligibility Criteria: 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.
Exclusion criteria:
- Age <18 years of age.
- Disease duration for >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 diseases (other than SSc) or overlap syndrome (eg, polymyositis/scleroderma).
- 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 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 DNA (HBV 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 ≤75% AND % predicted carbon monoxide 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 ≤ 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 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 cardiologist.)
- 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 ≥150 µmol/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 for pregnancy.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Argentina
Austria
Belgium
Estonia
France
Germany
Italy
Mexico
Poland
Romania
Russian Federation
Ukraine
United Kingdom
United States

Administrative Information

NCT Number:NCT02921971
Other Study ID Numbers
ACT14604
2016-001028-80
U1111-1179-4690
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Sanofi
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi