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Trial record 1 of 2 for:    IVA337
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Proof-of-concept Trial of IVA337 in Diffuse Cutaneous Systemic Sclerosis (FASST)

This study is currently recruiting participants.
Verified June 2016 by Inventiva Pharma
Sponsor:
ClinicalTrials.gov Identifier:
NCT02503644
First Posted: July 21, 2015
Last Update Posted: June 14, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Inventiva Pharma
  Purpose
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.

Condition Intervention Phase
Scleroderma, Diffuse Diffuse Cutaneous Systemic Sclerosis Drug: IVA337 Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Multicentre Proof-of-concept Trial of IVA337 in the Treatment of Diffuse Cutaneous Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Inventiva Pharma:

Primary Outcome Measures:
  • Measurement of skin thickness by the Modified Rodnan Skin Score (MRSS) [ Time Frame: 48 weeks ]
    Mean change of the MRSS from baseline


Secondary Outcome Measures:
  • Response rates based on MRSS improvement [ Time Frame: 12, 24, 32, 48, and 60 weeks ]
    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 [ Time Frame: 28, 32,40, and 48 weeks ]
    Overall progression of the disease: defined as absence of rescue therapy and absence of severe organ involvement

  • Lung function measured by FVC% predicted [ Time Frame: 24 and 48 weeks ]
    Change in pulmonary function

  • Lung function by cDLCO% predicted [ Time Frame: 24 and 48 weeks ]
    Change in pulmonary function

  • Scleroderma Health Assessment Questionnaire (SHAQ) [ Time Frame: 24, 48, and 60 weeks ]
    Changes in patient reported outcomes

  • Gastrointestinal tract symptoms severity and its impact on patients' well-being assessed by the UCLA SCTC GIT [ Time Frame: 24, 48, and 60 weeks ]
    Changes in patient reported outcomes

  • Patient-reported health status assessed by PROMIS29 [ Time Frame: 24, 48, and 60 weeks ]
    Changes in patient reported outcomes

  • Physical and mental health assessed by SF36 [ Time Frame: 24, 48, and 60 weeks ]
    Changes in patient reported outcomes

  • 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 [ Time Frame: 12, 24, 32, 48, and 60 weeks ]
    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

  • Hand function assessed by the Cochin Hand Function Scale [ Time Frame: 12, 24, 32, 48, and 60 weeks ]
  • Patient global assessment of disease activity assessed by a visual analogue scale [ Time Frame: 24, 48, and 60 weeks ]
    Patient global assessments of disease activity (VAS)

  • Physician global assessment of disease activity assessed by a visual analogue scale [ Time Frame: 24, 48, and 60 weeks ]
    Physician global assessment of disease activity (VAS)

  • Change in the Combined Response Index for Systemic Sclerosis (CRISS) [ Time Frame: 24, 48, and 60 weeks ]
    Composed of five variables: MRSS, FVC % predicted, physician and patient global assessments, and HAQ-DI score

  • Percent of patients who need escape therapy [ Time Frame: 28, 32,40, and 48 weeks ]
    Need for escape therapy

  • Percent of patients who experience a new severe organ involvement [ Time Frame: 2, 4, 8,12, 16, 24, 28, 32, 40, 48, and 60 weeks ]
    Severe organ involvement

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 2, 4, 8,12, 16, 24, 28, 32, 40, 48, and 60 weeks ]
    Frequency and type of AEs

  • Routine and specific laboratory tests (composite) to assess safety and tolerability [ Time Frame: 2, 12, 24, 32, 48, and 60 weeks ]
    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.


Other Outcome Measures:
  • Raynaud attacks assessed by a diary and the Raynaud condition score (VAS) [ Time Frame: Daily during week 9 and week 25 ]
  • Progression of the disease assessed by changes of the activity of specific SSc biomarkers in the blood [ Time Frame: 12, 24, and 48 weeks ]
    Mean changes in activity biomarkers

  • Progression of the disease assessed by changes of the activity of specific SSc biomarkers in the skin [ Time Frame: 48 weeks ]
    Mean changes in activity biomarkers

  • Population pharmacokinetics to confirm the pharmacokinetic profile, including Cmax, Tmax, AUC, half-life (t1/2), clearance (CL/F) and volume of distribution (Vd/F) [ Time Frame: 2, 24, and 48 weeks ]

Estimated Enrollment: 132
Study Start Date: October 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IVA337 800mg
Patients receive twice daily 400mg IVA337.
Drug: IVA337
Capsules of 200mg IVA337
Other Name: No other names at present
Active Comparator: IVA337 1200mg
Patients receive twice daily 600mg IVA337.
Drug: IVA337
Capsules of 200mg IVA337
Other Name: No other names at present
Placebo Comparator: Placebo
Patients receive twice daily placebo.
Drug: Placebo
Identical capsules without active substance
Other Name: No other names at present

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 12 weeks after the last dose.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Contraindications to the class of drugs under study (PPAR agonists), e.g. 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 in the last 3 months; rituximab in the last 6 months.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02503644


Contacts
Contact: Mari Carmen Delatte +33 380 447 680 mari-carmen.delatte@inventivapharma.com
Contact: Salim Kichou, Doctor +33 3 80 44 7589 salim.kichou@inventivapharma.com

  Show 43 Study Locations
Sponsors and Collaborators
Inventiva Pharma
Investigators
Principal Investigator: 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
  More Information

Responsible Party: Inventiva Pharma
ClinicalTrials.gov Identifier: NCT02503644     History of Changes
Other Study ID Numbers: IVA_01_337_HSSC_15_001
First Submitted: June 30, 2015
First Posted: July 21, 2015
Last Update Posted: June 14, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Inventiva Pharma:
diffuse cutaneous systemic sclerosis
scleroderma
IVA337
dcSSc

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases