Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis

NCT ID: NCT02921971

Last Updated: 2022-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-21
• Study Completion Date: 2019-04-01

Brief 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.

Detailed Description

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

Conditions

Systemic Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo (for SAR156597), single subcutaneous (SC) injection once in a week (QW) up to Week 24.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous

SAR156597

SAR156597 200 milligram (mg), single SC injection QW up to Week 24.

Group Type: EXPERIMENTAL

SAR156597

Intervention Type: DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous

Interventions

SAR156597

Pharmaceutical form: Solution Route of administration: Subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: Solution Route of administration: Subcutaneous

Intervention Type: DRUG

Other Intervention Names

Romilkimab

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400006

San Francisco, California, United States

Investigational Site Number 8400005

Washington D.C., District of Columbia, United States

Investigational Site Number 8400002

Cleveland, Ohio, United States

Investigational Site Number 8400007

Houston, Texas, United States

Investigational Site Number 0320003

Buenos Aires, , Argentina

Investigational Site Number 0320002

Caba, , Argentina

Investigational Site Number 0320005

Capital Federal, , Argentina

Investigational Site Number 0320001

San Miguel de Tucumán, , Argentina

Investigational Site Number 0560001

Ghent, , Belgium

Investigational Site Number 0560002

Leuven, , Belgium

Investigational Site Number 2330001

Tallinn, , Estonia

Investigational Site Number 2500003

Montpellier, , France

Investigational Site Number 2500004

Paris, , France

Investigational Site Number 2500002

Strasbourg, , France

Investigational Site Number 2760003

Bad Nauheim, , Germany

Investigational Site Number 2760001

Berlin, , Germany

Investigational Site Number 2760002

Cologne, , Germany

Investigational Site Number 2760004

Ulm, , Germany

Investigational Site Number 3800004

Genova, , Italy

Investigational Site Number 3800001

Milan, , Italy

Investigational Site Number 3800005

Milan, , Italy

Investigational Site Number 3800006

Orbassano, , Italy

Investigational Site Number 4840001

Chihuahua City, , Mexico

Investigational Site Number 4840005

Guadalajara, , Mexico

Investigational Site Number 4840002

Guadalajara, , Mexico

Investigational Site Number 4840003

Monterrey, , Mexico

Investigational Site Number 6160001

Poznan, , Poland

Investigational Site Number 6160002

Warsaw, , Poland

Investigational Site Number 6160003

Wroclaw, , Poland

Investigational Site Number 6420003

Bucharest, , Romania

Investigational Site Number 6420004

Bucharest, , Romania

Investigational Site Number 6420005

Bucharest, , Romania

Investigational Site Number 6420001

Cluj-Napoca, , Romania

Investigational Site Number 6420002

Târgu Mureş, , Romania

Investigational Site Number 6430002

Kemerovo, , Russia

Investigational Site Number 6430005

Moscow, , Russia

Investigational Site Number 6430001

Moscow, , Russia

Investigational Site Number 6430004

Moscow, , Russia

Investigational Site Number 6430003

Ufa, , Russia

Investigational Site Number 8040001

Kyiv, , Ukraine

Investigational Site Number 8040002

Kyiv, , Ukraine

Investigational Site Number 8040004

Kyiv, , Ukraine

Investigational Site Number 8040003

Kyiv, , Ukraine

Investigational Site Number 8260001

London, , United Kingdom

Countries

United States; Argentina; Belgium; Estonia; France; Germany; Italy; Mexico; Poland; Romania; Russia; Ukraine; United Kingdom

References

Allanore Y, Wung P, Soubrane C, Esperet C, Marrache F, Bejuit R, Lahmar A, Khanna D, Denton CP; Investigators. A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2020 Dec;79(12):1600-1607. doi: 10.1136/annrheumdis-2020-218447. Epub 2020 Sep 22.

Reference Type: DERIVED

PMID: 32963047 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001028-80

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1179-4690

Identifier Type: OTHER

Identifier Source: secondary_id

ACT14604

Identifier Type: -

Identifier Source: org_study_id