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Scleroderma, DiffusePhase 2FASSTNCT02503644

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

A Phase 2 study testing IVA337 in people with Scleroderma, Diffuse and Diffuse Cutaneous Systemic Sclerosis, run by Inventiva Pharma at 49 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
IVA337
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
145 participants
Where
49 sitesin 10 countries
Study dates
29 Oct 2015to 12 Oct 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 20Show fewer
  • 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.

Trial locations and contacts

49 sites in 10 countries.

49 sites in 10 countries

Germany10 sites

  • Kerckhoff-Klinik

    Bad Nauheim, 61231

  • Charité- Universitätsmedizin Berlin

    Berlin, 10117

  • Chaité-Universtätsmedezin Berlin

    Berlin

  • Klinik fur Dermatologie und Venerologie der Universitat zu Köln

    Cologne, 50931

  • Univertaetsklinikum Carl Gustav Carus

    Dresden, 01307

  • University of Erlangen-Nuremberg

    Erlangen, 91054

  • CIRI GmbH Centrum für Innovative Diagnostik und Therapie

    Frankfurt

  • University Medical Center Freiburg

    Freiburg im Breisgau, 79106

  • Kilinik für Hautkrankenheiten

    Münster, 48149

  • Universtätsklinik Ulm

    Ulm, 89081

Other trials in Germany

Italy9 sites

  • Istituto di Clinica Medica Generale Polo Didattico

    Ancona, 60020

  • Azienda Ospedalaria Spedali Civili di Brescia

    Brescia, 25123

  • Azienda Ospedaliera Universitaria Careggi

    Florence, 50139

  • Ospedale San Salvatore ASL L'Aquila

    L’Aquila, 67100

  • Azienda Ospedaliera Universitaria Federico II

    Naples, 80131

  • University of Padova

    Padova, 35128

  • Ospedale di Alta Specializzazione "San Camillo"

    Roma, 00152

  • Policlinico Umberto I

    Roma, 00161

  • Universita degli Studi de Verona

    Verona, 37134

Other trials in Italy

Spain8 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08026

  • Hopital Universitario Gregorio Marañon

    Madrid, 28007

  • Hopital 12 de Octubre

    Madrid, 28041

  • Hopital Universitario Sanchinarro

    Madrid, 28050

  • Hospital La Paz

    Madrid

  • Hospital La Princesa

    Madrid

  • Hospital Universitario Ramon y Cajal

    Madrid

  • Hospital Universitario Dr Peset

    Valencia, 46017

Other trials in Spain

Poland6 sites

  • Centrum Miriada Prywatny

    Bialystok

  • University Hospital in Bydgoszcz

    Bydgoszcz

  • CM Plejady

    Krakow

  • Reumed

    Lublin

  • Medycine Centrum Hetmanska Poznan

    Poznan

  • Centrum Medyczne Oporow

    Wroclaw

Other trials in Poland

Bulgaria4 sites

  • University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski

    Pleven

  • Multiprofile Hospital for Active Treatment Plovdiv

    Plovdiv

  • University Multiprofile Hospital for Active Treatment -Kaspela

    Plovdiv

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

    Sofia

Other trials in Bulgaria

France4 sites

  • Hôpital Pellegrin

    Bordeaux, 33076

  • CHRU de Lille- Hôpital Claude Huriez

    Lille, 59037

  • Hopital Cochin

    Paris, 75014

  • University Hospital of Strasbourg

    Strasbourg, 67098

Other trials in France

Netherlands2 sites

  • Leiden University Medical Center

    Leiden

  • Erasmus MC Universitair Medisch Centrum Rotterdam

    Rotterdam

Other trials in Netherlands

Slovenia2 sites

  • University Medical centre Ljubljana

    Ljubljana

  • University Medical Centre Maribor

    Maribor

Other trials in Slovenia

Switzerland2 sites

  • University Hospital Lausanne

    Lausanne

  • University Hospital Zurich

    Zurich

Other trials in Switzerland

United Kingdom2 sites

  • Leeds Institut of Rheumatic and Musculoskeletal Medicine

    Leeds, LS7 4SA

  • Royal Free Hospital

    London, NW3 2QG

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Multicentre Proof-of-concept Trial of IVA337 in the Treatment of Diffuse Cutaneous Systemic Sclerosis

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.

Read the 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.

Being tested
IVA337, Placebo
Keywords
diffuse cutaneous systemic sclerosis, scleroderma, IVA337, dcSSc, lanifibranor
Medical subject headings
Scleroderma, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IVA337Drug

    Also called lanifibranor

    Capsules of 200mg IVA337

  • PlaceboDrug

    Also called No other names at present

    Identical capsules without active substance

Study groups in NCT02503644
Study groupRoleWhat they receive
IVA337 800mgActive comparatorPatients receive twice daily 400mg IVA337.
Receives: Drug: IVA337
IVA337 1200mgActive comparatorPatients receive twice daily 600mg IVA337.
Receives: Drug: IVA337
PlaceboPlacebo comparatorPatients receive twice daily placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Mean change of the MRSS from baseline

    Measured: 48 weeks

Secondary outcomes (17)

  1. Response rates based on MRSS improvement

    MRSS response rates:

    Initial definition: improvers are defined by a reduction ≥5 points and ≥25 % of MRSS; Additional definition: improvers are defined by a reduction

    ≥ 4 points and ≥ 20% of MRSS based on Quillinan et al. (2014, 2017)

    Measured: 12, 24, 32, 48 weeks

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

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

    Measured: 28, 32,40, and 48 weeks

  3. Lung function measured by FVC% predicted

    Change in pulmonary function

    Measured: 24 and 48 weeks

  4. Lung function by cDLCO% predicted

    Change in pulmonary function

    Measured: 24 and 48 weeks

  5. Scleroderma Health Assessment Questionnaire (SHAQ)

    Changes in patient reported outcomes

    Measured: 24 and 48 weeks

  6. Gastrointestinal tract symptoms severity and its impact on patients' well-being assessed by the UCLA SCTC GIT

    Changes in patient reported outcomes

    Measured: 24 and 48 weeks

  7. Patient-reported health status assessed by PROMIS29

    Changes in patient reported outcomes

    Measured: 24 and 48 weeks

  8. Physical and mental health assessed by SF36

    Changes in patient reported outcomes

    Measured: 24 and 48 weeks

  9. 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

    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

    Measured: 12, 24, 32 and 48 weeks

  10. Hand function assessed by the Cochin Hand Function Scale

    Hand function assessed by the Cochin Hand Function Scale

    Measured: 12, 24, 32 and 48 weeks

  11. Patient global assessment of disease activity assessed by a visual analogue scale

    Patient global assessments of disease activity (VAS)

    Measured: 24 and 48 weeks

  12. Physician global assessment of disease activity assessed by a visual analogue scale

    Physician global assessment of disease activity (VAS)

    Measured: 24 and 48 weeks

  13. Change in the Combined Response Index for Systemic Sclerosis (CRISS)

    Composed of five variables: MRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score

    Measured: 24 and 48 weeks

  14. Percent of patients who need escape therapy

    Need for escape therapy

    Measured: 28, 32,40, and 48 weeks

  15. Percent of patients who experience a new severe organ involvement

    Severe organ involvement

    Measured: 2, 4, 8,12, 16, 24, 28, 32, 40, 48, and 52 weeks

  16. Number of participants with adverse events as a measure of safety and tolerability

    Frequency and type of AEs

    Measured: 2, 4, 8, 12, 16, 20, 24, 28, 32, 40, 44, 48, and 52 weeks

  17. Routine and specific laboratory tests (composite) to assess safety and tolerability

    creatine kinase, N-terminal pro-brain natriuretic peptide, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, γ-glutamyl transferase, total bilirubin, direct bilirubin,RBC and WBC count, reticulocytes, haemoglobin, haematocrit, albumin , Quick, aPTT, INR, BUN, plasma creatinine, microalbuminuria, homocysteine, urinalysis (dip stick), glycated haemoglobin, creatine phosphokinase increase, platelet counts, plasma osteocalcin, serum beta C-terminal telopeptide (β-CTx or B-Crosslaps), Differential: neutrophils, eosinophils, basophils, monocytes, lymphocytes, cholesterol, triglycerides, albumin, total protein, C-reactive protein (CRP), adiponectin, serology HIV and hepatitis infection: Hep. A antibodies, B antibodies and antigen, C antibodies, serum b-HCG.

    Measured: 2, 12, 20, 24, 32, 36, 44, 48, and 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2015 (estimated)
  2. Study start29 Oct 2015
  3. Primary completionOct 2018
  4. Study completion12 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02503644
Sponsor's protocol ID
IVA_01_337_HSSC_15_001
Acronym
FASST
Status last verified
Mar 2019
First submitted
30 Jun 2015
Last updated
4 Mar 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IVA337 in people with Scleroderma, Diffuse and Diffuse Cutaneous Systemic Sclerosis, run by Inventiva Pharma at 49 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in Germany, Italy, Spain, Poland, Bulgaria and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of skin thickness by the Modified Rodnan Skin Score (MRSS) (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02503644.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2019.

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