Proof-of-concept Trial of IVA337 in Diffuse Cutaneous Systemic Sclerosis

NCT ID: NCT02503644

Last Updated: 2019-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-29
• Study Completion Date: 2018-10-12

Brief Summary

Systemic sclerosis (SSc), or scleroderma is a connective tissue disease of autoimmune origin. It is a life-threatening orphan disease with severe physical and psychosocial consequences. IVA337 has a novel mechanism of action and this study is designed to compare IVA337 at two dose levels with a placebo control treatment. Patients will be unaware of the treatment they are receiving and will be randomized to one of three treatment arms , either IVA337 400mg bid, IVA337 600mg bid or placebo bid. They will receive drug for 48 weeks and during that time assessments will be made to monitor both the efficacy and safety of the treatment.

Detailed Description

Study design: randomized, double-blind, placebo-controlled, multicentre phase 2 proof-of-concept trial of IVA337 for the treatment DcSSc.

The treatments are randomly assigned. The randomisation is stratified for background therapy to ensure even distribution of background therapies among treatment groups.

There are 3 parallel treatment groups: placebo, IVA337 400mg bid and IVA337 600mg bid (identical capsules of 200mg IVA337 or placebo). Both, patient and investigator are blinded.

The treatment lasts 48 weeks. A follow-up assessment takes place 4 weeks after the last dose.

Conditions

Scleroderma, Diffuse; Diffuse Cutaneous Systemic Sclerosis

Study Design

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

Study Groups

IVA337 800mg

Patients receive twice daily 400mg IVA337.

Group Type: ACTIVE_COMPARATOR

IVA337

Intervention Type: DRUG

Capsules of 200mg IVA337

IVA337 1200mg

Patients receive twice daily 600mg IVA337.

Group Type: ACTIVE_COMPARATOR

IVA337

Intervention Type: DRUG

Capsules of 200mg IVA337

Placebo

Patients receive twice daily placebo.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical capsules without active substance

Interventions

IVA337

Capsules of 200mg IVA337

Intervention Type: DRUG

Placebo

Identical capsules without active substance

Intervention Type: DRUG

Other Intervention Names

lanifibranor; No other names at present

Eligibility Criteria

Inclusion Criteria

• Informed Consent documented by signature
• Systemic sclerosis according to ACR/EULAR 2103 criteria (van de Hoogen 2013)
• Diffuse cutaneous SSc subset according to LeRoy's criteria
• Diagnosis within the past 3 years as defined by the first non-Raynaud's symptom
• MRSS between 10 and 25
• Age between 18 and 75, male or female

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; the therapy must be maintained as background therapy.

Exclusion Criteria

• 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 30 ml/min (CKD-EPI or MDRD formula) 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
• History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma, 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 4 weeks before the Pre-treatment Visit
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inventiva Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yannick Allanore, Professor

Role: PRINCIPAL_INVESTIGATOR

Université Paris Descartes, Hôpital Cochin, Service de Rhumatologie A & INSERM, Paris, France,

Christopher Denton, Professor

Role: PRINCIPAL_INVESTIGATOR

Royal Free Hospital NHS Foundation Trust

Locations

University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment -Kaspela

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment - "Sveti Ivan Rilski"

Sofia, , Bulgaria

Hôpital Pellegrin

Bordeaux, , France

CHRU de Lille- Hôpital Claude Huriez

Lille, , France

Hopital Cochin

Paris, , France

University Hospital of Strasbourg

Strasbourg, , France

Kerckhoff-Klinik

Bad Nauheim, , Germany

Charité- Universitätsmedizin Berlin

Berlin, , Germany

Chaité-Universtätsmedezin Berlin

Berlin, , Germany

Klinik fur Dermatologie und Venerologie der Universitat zu Köln

Cologne, , Germany

Univertaetsklinikum Carl Gustav Carus

Dresden, , Germany

University of Erlangen-Nuremberg

Erlangen, , Germany

CIRI GmbH Centrum für Innovative Diagnostik und Therapie

Frankfurt, , Germany

University Medical Center Freiburg

Freiburg im Breisgau, , Germany

Kilinik für Hautkrankenheiten

Münster, , Germany

Universtätsklinik Ulm

Ulm, , Germany

Istituto di Clinica Medica Generale Polo Didattico

Ancona, , Italy

Azienda Ospedalaria Spedali Civili di Brescia

Brescia, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Ospedale San Salvatore ASL L'Aquila

L’Aquila, , Italy

Azienda Ospedaliera Universitaria Federico II

Napoli, , Italy

University of Padova

Padua, , Italy

Ospedale di Alta Specializzazione "San Camillo"

Roma, , Italy

Policlinico Umberto I

Roma, , Italy

Universita degli Studi de Verona

Verona, , Italy

Leiden University Medical Center

Leiden, , Netherlands

Erasmus MC Universitair Medisch Centrum Rotterdam

Rotterdam, , Netherlands

Centrum Miriada Prywatny

Bialystok, , Poland

University Hospital in Bydgoszcz

Bydgoszcz, , Poland

CM Plejady

Krakow, , Poland

Reumed

Lublin, , Poland

Medycine Centrum Hetmanska Poznan

Poznan, , Poland

Centrum Medyczne Oporow

Wroclaw, , Poland

University Medical centre Ljubljana

Ljubljana, , Slovenia

University Medical Centre Maribor

Maribor, , Slovenia

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hopital Universitario Gregorio Marañon

Madrid, , Spain

Hopital 12 de Octubre

Madrid, , Spain

Hopital Universitario Sanchinarro

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital La Princesa

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario Dr Peset

Valencia, , Spain

University Hospital Lausanne

Lausanne, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

Leeds Institut of Rheumatic and Musculoskeletal Medicine

Leeds, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Countries

Bulgaria; France; Germany; Italy; Netherlands; Poland; Slovenia; Spain; Switzerland; United Kingdom

Other Identifiers

IVA_01_337_HSSC_15_001

Identifier Type: -

Identifier Source: org_study_id