A clinical trial to investigate the efficacy and safety of a new compound for the treatment of diffuse systemic sclerosis, called IVA337.Patients in the trial will be randomly allocated to either the new treatment or a placebo and will be unaware of which treatment they are receiving.
- Conditions
- Systemic sclerosis (scleroderma) (SSc) is a chronic connective tissue disorder of unknown aetiology characterized by widespread microvascular damage and excessive deposition of collagen in the skin and internal organs.MedDRA version: 20.0Level: LLTClassification code 10012941Term: Diffuse sclerodermaSystem Organ Class: 100000004859MedDRA version: 20.0Level: LLTClassification code 10074034Term: Generalised sclerodermaSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2015-001617-27-SI
- Lead Sponsor
- Inventiva SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 145
•Systemic sclerosis according to ACR/EULAR 2013 criteria
•Diffuse cutaneous SSc subset (LeRoy’s criteria)
•Diagnosis within the past 3 years as defined by the first non-Raynaud’s symptom
•MRSS between 10 and 25
• Aged between 18 and 75 years
• Informed consent documented by signature
• Patients on stable treatment (for >3 months) with prednisone = 10 mg, methotrexate= 20 mg/w, azathioprine = 150 mg/d, mycophenolate mofetil = 2g/d, or leflunomide = 20 mg/d may be included in the study; therapy to be maintained as background therapy
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 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35
• Cyclophosphamide during the past 3 months
• Requirement of IV prostanoids for pulmonary hypertension in the last 3 months
• Renal insufficiency defined by a creatinine clearance of less than 30ml/min (CKD-EPI or MDRD formula) a and/or past/current renal crisis
• Hepatic impairment i.e. primary biliary cirrhosis and unexplained persistent liver function abnormality,
• Gallbladder disease (Cholelithiasis is not an exclusion criterion)
• Diabetic ketoacidosis
• Severe cardiac (LVEF <45%) and/or pulmonary disease (FVC < 50% or pulmonary hypertension proven by right heart catheterisation)
• History of heart failure, symptomatic coronary artery disease, significant ventricular tachyarrhythmia, stent placement, coronary artery bypass surgery, and/or myocardial infarction.
• Recipient of solid organ transplant
• Gastrointestinal involvement preventing oral administration of study drug
• Chronic infections, positive serology for infection with hepatitis B or C.
• Pregnancy, Lactation. Woman of childbearing potential unwilling to use a medically acceptable form of birth control. Such methods include:
- combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
- progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
- intrauterine device (IUD)
- intrauterine hormone-releasing system ( IUS)
- bilateral tubal occlusion
- vasectomised partner
• History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma of the skin, treated cervical dysplasia, or treated in situ cervical cancer
• A recent history of alcohol or drug abuse, non-compliance with other medical therapies
• Participation in a clinical study involving another investigational drug or device within the past 4 weeks or during the study
• Laboratory parameters at the pre-treatment visit showing any of the following abnormal results: transaminases > 2x the upper limit of normal (ULN) and/or bilirubin > 2x ULN; neutrophil count < 1,500/mm3; platelet count < 100,000/mm3; haemoglobin < 9 g/dL
• known hypersensitivity or allergy to class of drugs or the investigational product
• Any condition or treatment, which in the opinion of the investigator, places the subject at unacceptable risk as a patient in the trial
• Co-therapy with biologics. Wash-out period: Any anti-TNF agent in the last 3-months: adalimumab, certolizumab, etanercept, golimumab,
infliximab, abatacept and tocilizumab in the last 3 months; rituximab in the last 6 months
• Any other significant heart disease or any clinically significant ECG abnormality reported by central ECG reading
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to evaluate in patients suffering from diffuse cutaneous SSc (DcSSc) the effect of 800mg and 1200mg IVA337 daily on the skin compared to placebo. The modified Rodnan Skin Score (MRSS) will be used to determine the changes in skin.<br>;Secondary Objective: Secondary objectives include additional efficacy evaluations (details in the protocol), assessment of adverse events (AEs), and determination of population PK parameters of IVA337 in patients.<br>;Primary end point(s): Primary outcome is the mean change of the Modifed Rodnan Skin Score (MRSS) from baseline to week 48;Timepoint(s) of evaluation of this end point: 48 weeks
- Secondary Outcome Measures
Name Time Method