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

NCT02503644 | Completed Phase 2

• 1 other identifier: IVA_01_337_HSSC_15_001
• Study Type: interventional
• Target: 145
• Locations: 10 countries
• Sites: 49

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.

Conditions

Scleroderma, Diffuse; Diffuse Cutaneous Systemic Sclerosis

Keywords

diffuse cutaneous systemic sclerosis; scleroderma; IVA337; dcSSc; lanifibranor

Outcome Measures

Primary Outcomes (1)

• Measurement of skin thickness by the Modified Rodnan Skin Score (MRSS)

  Mean change of the MRSS from baseline

  48 weeks

Secondary Outcomes (17)

• Response rates based on MRSS improvement

  12, 24, 32, 48 weeks

• Overall progression of the disease: defined as absence of rescue therapy and absence of severe organ involvement

  28, 32,40, and 48 weeks

• Lung function measured by FVC% predicted

  24 and 48 weeks

• Lung function by cDLCO% predicted

  24 and 48 weeks

• Scleroderma Health Assessment Questionnaire (SHAQ)

  24 and 48 weeks

Other Outcomes (4)

• Raynaud attacks assessed by a diary and the Raynaud condition score (VAS)

  Daily during week 9 and week 25

• Progression of the disease assessed by changes of the activity of specific SSc biomarkers in the blood

  12, 24, and 48 weeks

• Progression of the disease assessed by changes of the activity of specific SSc biomarkers in the skin

  48 weeks

Study Arms (3)

IVA337 800mg

ACTIVE COMPARATOR

Patients receive twice daily 400mg IVA337.

Drug: IVA337

IVA337 1200mg

ACTIVE COMPARATOR

Patients receive twice daily 600mg IVA337.

Drug: IVA337

Placebo

PLACEBO COMPARATOR

Patients receive twice daily placebo.

Drug: Placebo

Interventions

IVA337 DRUG

Capsules of 200mg IVA337

Also known as: lanifibranor

IVA337 1200mg; IVA337 800mg

Placebo DRUG

Identical capsules without active substance

Also known as: No other names at present

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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

Sponsors & Collaborators

• Inventiva Pharma: lead

Study Sites (49)

University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski

Pleven, Bulgaria

Location

Multiprofile Hospital for Active Treatment Plovdiv

Plovdiv, Bulgaria

Location

University Multiprofile Hospital for Active Treatment -Kaspela

Plovdiv, Bulgaria

Location

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

Sofia, Bulgaria

Location

Hôpital Pellegrin

Bordeaux, 33076, France

Location

CHRU de Lille- Hôpital Claude Huriez

Lille, 59037, France

Location

Hopital Cochin

Paris, 75014, France

Location

University Hospital of Strasbourg

Strasbourg, 67098, France

Location

Kerckhoff-Klinik

Bad Nauheim, 61231, Germany

Location

Charité- Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Chaité-Universtätsmedezin Berlin

Berlin, Germany

Location

Klinik fur Dermatologie und Venerologie der Universitat zu Köln

Cologne, 50931, Germany

Location

Univertaetsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

CIRI GmbH Centrum für Innovative Diagnostik und Therapie

Frankfurt, Germany

Location

University Medical Center Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Kilinik für Hautkrankenheiten

Münster, 48149, Germany

Location

Universtätsklinik Ulm

Ulm, 89081, Germany

Location

Istituto di Clinica Medica Generale Polo Didattico

Ancona, 60020, Italy

Location

Azienda Ospedalaria Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50139, Italy

Location

Ospedale San Salvatore ASL L'Aquila

L’Aquila, 67100, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

University of Padova

Padua, 35128, Italy

Location

Ospedale di Alta Specializzazione "San Camillo"

Roma, 00152, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Universita degli Studi de Verona

Verona, 37134, Italy

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Erasmus MC Universitair Medisch Centrum Rotterdam

Rotterdam, Netherlands

Location

Centrum Miriada Prywatny

Bialystok, Poland

Location

University Hospital in Bydgoszcz

Bydgoszcz, Poland

Location

CM Plejady

Krakow, Poland

Location

Reumed

Lublin, Poland

Location

Medycine Centrum Hetmanska Poznan

Poznan, Poland

Location

Centrum Medyczne Oporow

Wroclaw, Poland

Location

University Medical centre Ljubljana

Ljubljana, Slovenia

Location

University Medical Centre Maribor

Maribor, Slovenia

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08026, Spain

Location

Hopital Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hopital 12 de Octubre

Madrid, 28041, Spain

Location

Hopital Universitario Sanchinarro

Madrid, 28050, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital La Princesa

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario Dr Peset

Valencia, 46017, Spain

Location

University Hospital Lausanne

Lausanne, Switzerland

Location

University Hospital Zurich

Zurich, Switzerland

Location

Leeds Institut of Rheumatic and Musculoskeletal Medicine

Leeds, LS7 4SA, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

lanifibranor

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Yannick Allanore, Professor

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

  PRINCIPAL INVESTIGATOR

• Christopher Denton, Professor

  Royal Free Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 21, 2015
• Study Start: October 29, 2015
• Primary Completion: October 1, 2018
• Study Completion: October 12, 2018
• Last Updated: March 4, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); ES (8); CH (2); BU (4); FR (4); GB (2); DE (10); SL (2); IT (9); PL (6)