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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary:

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.

Current Primary Outcome: Measurement of skin thickness by the Modified Rodnan Skin Score (MRSS) [ Time Frame: 48 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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.

Original Secondary Outcome:

• 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 analgue 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 analgue 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 tolerabiltiy [ Time Frame: 2, 12, 24, 32, 48, and 60 weeks ]
  creatine kinase, troponin I, 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.

Dates:
Date Received: June 30, 2015
Date Started: October 2015
Date Completion: December 2017
Last Updated: June 13, 2016
Last Verified: June 2016