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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02503644
• Date of registration: 30/06/2015
• Prospective Registration: Yes
• Primary sponsor: Inventiva Pharma
• Public title: Proof-of-concept Trial of IVA337 in Diffuse Cutaneous Systemic Sclerosis FASST
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Multicentre Proof-of-concept Trial of IVA337 in the Treatment of Diffuse Cutaneous Systemic Sclerosis
• Date of first enrolment: October 29, 2015
• Target sample size: 145
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02503644
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Christopher Denton, Professor
• Affiliation: Royal Free Hospital NHS Foundation Trust

• Name: Yannick Allanore, Professor
• Affiliation: Université Paris Descartes, Hôpital Cochin, Service de Rhumatologie A & INSERM, Paris, France,

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diffuse Cutaneous Systemic Sclerosis

Scleroderma, Diffuse

Intervention(s)

Drug: Placebo

Drug: IVA337

Primary Outcome(s)

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

Secondary Outcome(s)

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

Physical and mental health assessed by SF36 [Time Frame: 24 and 48 weeks]

Lung function by cDLCO% predicted [Time Frame: 24 and 48 weeks]

Routine and specific laboratory tests (composite) to assess safety and tolerability [Time Frame: 2, 12, 20, 24, 32, 36, 44, 48, and 52 weeks]

Change in the Combined Response Index for Systemic Sclerosis (CRISS) [Time Frame: 24 and 48 weeks]

Number of participants with adverse events as a measure of safety and tolerability [Time Frame: 2, 4, 8, 12, 16, 20, 24, 28, 32, 40, 44, 48, and 52 weeks]

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]

Physician global assessment of disease activity assessed by a visual analogue scale [Time Frame: 24 and 48 weeks]

Patient global assessment of disease activity assessed by a visual analogue scale [Time Frame: 24 and 48 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 [Time Frame: 12, 24, 32 and 48 weeks]

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

Percent of patients who experience a new severe organ involvement [Time Frame: 2, 4, 8,12, 16, 24, 28, 32, 40, 48, and 52 weeks]

Response rates based on MRSS improvement [Time Frame: 12, 24, 32, 48 weeks]

Patient-reported health status assessed by PROMIS29 [Time Frame: 24 and 48 weeks]

Gastrointestinal tract symptoms severity and its impact on patients' well-being assessed by the UCLA SCTC GIT [Time Frame: 24 and 48 weeks]

Hand function assessed by the Cochin Hand Function Scale [Time Frame: 12, 24, 32 and 48 weeks]

Scleroderma Health Assessment Questionnaire (SHAQ) [Time Frame: 24 and 48 weeks]

Secondary ID(s)

IVA_01_337_HSSC_15_001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors