Clinical trial NCT02921971: Effectiveness and Safety of SAR156597 in Treating Diffuse Systemic Sclerosis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-10-03
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Modified Rodnan Skin Score to Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Mean Observed Forced Vital Capacity (FVC) Level to Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Mean Observed Diffusing Lung Capacity for Carbon Monoxide (DLco) to Week 24
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Investigational Site Number 8400006
state: California
city: Washington
country: United States
facility: Investigational Site Number 8400005
state: District of Columbia
city: Cleveland
country: United States
facility: Investigational Site Number 8400002
state: Ohio
city: Houston
country: United States
facility: Investigational Site Number 8400007
state: Texas
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0320003
city: Caba
country: Argentina
facility: Investigational Site Number 0320002
city: Capital Federal
country: Argentina
facility: Investigational Site Number 0320005
city: San Miguel De Tucuman
country: Argentina
facility: Investigational Site Number 0320001
city: Gent
country: Belgium
facility: Investigational Site Number 0560001
city: Leuven
country: Belgium
facility: Investigational Site Number 0560002
city: Tallinn
country: Estonia
facility: Investigational Site Number 2330001
city: Montpellier
country: France
facility: Investigational Site Number 2500003
city: Paris Cedex 14
country: France
facility: Investigational Site Number 2500004
city: Strasbourg Cedex
country: France
facility: Investigational Site Number 2500002
city: Bad Nauheim
country: Germany
facility: Investigational Site Number 2760003
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
city: Köln
country: Germany
facility: Investigational Site Number 2760002
city: Ulm
country: Germany
facility: Investigational Site Number 2760004
city: Genova
country: Italy
facility: Investigational Site Number 3800004
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Milano
country: Italy
facility: Investigational Site Number 3800005
city: Orbassano
country: Italy
facility: Investigational Site Number 3800006
city: Chihuahua
country: Mexico
facility: Investigational Site Number 4840001
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840005
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4840002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840003
city: Poznan
country: Poland
facility: Investigational Site Number 6160001
city: Warszawa
country: Poland
facility: Investigational Site Number 6160002
city: Wroclaw
country: Poland
facility: Investigational Site Number 6160003
city: Bucharest
country: Romania
facility: Investigational Site Number 6420003
city: Bucharest
country: Romania
facility: Investigational Site Number 6420004
city: Bucuresti
country: Romania
facility: Investigational Site Number 6420005
city: Cluj Napoca
country: Romania
facility: Investigational Site Number 6420001
city: Targu Mures
country: Romania
facility: Investigational Site Number 6420002
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430004
city: Ufa
country: Russian Federation
facility: Investigational Site Number 6430003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040001
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040002
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040004
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040003
city: London
country: United Kingdom
facility: Investigational Site Number 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.