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 . Pulmonary fibrosis and pulmonary hypertension appear as the leading causes of mortality and patients with SSc have considerable morbidity from their disease due to skin fibrosis, Raynaud’s phenomenon and damage to the gastrointestinal tract, lungs, heart and kidneys. MedDRA v
Conditions
Interventions
Product Name: IVA337
Product Code: IVA337
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: IVA337
CAS Number: 927961-18-0
Current Sponsor code: IVA337
Other descriptive name: 1-(6-BENZOTHIAZOLY
Sponsors
Inventiva SAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 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 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Unstable treatment with corticosteroids or immunosuppressive agents (stable therapy for more than 3 months with prednisone = 10 mg, methotrexate= 20 mg/w, azathioprine = 150 mg/d, mycofenolate mofetil = 2g/d, or leflunomide = 20 mg/d is acceptable) • Cyclophosphamide during the past 6 months • Requirement of IV prostanoids for critical ischemia or pulmonary hypertension in the last 3 months • Renal insufficiency defined by a creatinine clearance of less than 30 ml/min and/or past/current renal crisis • Hepatic impairment i.e. primary biliary cirrhosis and unexplained persistent liver function abnormality, • Gallbladder disease • Severe cardiac (LVEF 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 • Contraindications to the class of drugs under study (PPAR agonists), e.g. known hypersensitivity or allergy to class of drugs or the investigational product (see IB 2015) • Any condition or treatment, which in the opinion of the investigator, places the subject at unacceptable risk as a patient in the trial (Please consider the precautions and warnings described in the IB 2015)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ;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. ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): • MRSS response rates; improvers are defined by a reduction =5 points and =25 % of MRSS • Overall progression of the disease: defined as absence of rescue therapy and absence of severe organ involvement (see definition below) • Change in pulmonary function (FVC% predicted and cDLCO% predicted) • Changes in patient reported outcomes (SHAQ, UCLA SCTC GIT, PROMIS29, SF36) • Digital ulcer net burden (defined as total number of ulcers at a certain time point minus number of ulcers at baseline) and proportion of patients who do not develop new ulcers • Cochin Hand Function Scale • Physician and patient global assessments of disease activity over the past week (VAS) • Change in the Combined Response Index for Systemic Sclerosis (CRISS), consisting of five variables: MRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score (from SHAQ patient reported outcome) • Need for escape therapy (% patients) • Severe organ involvement (% patients) defined by • New renal crisis OR • New or worsened clinically symptomatic and significant heart disease, considered secondary to DcSSc OR • Relative decline in FVC % predicted by = 10% or relative decline in FVC % predicted between 5 to 8 and swollen joints > 6 OR • New onset of tendon friction rubs SAFETY • Frequency and type of AEs • Lab tests: mean change and frequency of values outside the normal range OTHER • Changes in Raynaud phenomenon (Raynaud’s condition score) • Mean changes in activity biomarkers • Population pharmacokinetics • Follow-up: There is a follow-up visit to evaluate any changes that might occur within 12 weeks after completion of the treatment. The performed assessments listed in the Schedule of Study Procedures refer to safety and efficacy.;Timepoint(s) of evaluation of this end point: Throughout the study at weeks, 2, 4, 8, 12, 16, 24, 28, 32, 40, 48, 60 | — |
Countries
Bulgaria, Germany, Italy, Netherlands, Slovenia, Spain, Switzerland, United Kingdom
Contacts
Public ContactManager
Inventiva
Outcome results
None listed