A multi-centre, open-label, Proof of Concept (PoC) study to evaluate the efficacy and tolerability of STI571 for the treatment of fibrosis in patients with systemic sclerosis - ND

Conditions: sistemic sclerosis
MedDRA version: 9.1Level: LLTClassification code 10018124Term: Generalized scleroderma

Registration Number: EUCTR2007-004669-17-IT

Lead Sponsor: OVARTIS FARMA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 27

Inclusion Criteria

Male and female patients equal to or older than 18 years of age and fulfilling the American College of Rheumatology criteria for systemic sclerosis (SSc) Diffuse cutaneous SSc (dcSSc) according to the LeRoy criteria with disease duration less than 18 months from the appearance of the first non-RaynaudŽs symptom judged by a physician to be part of SSc Patients with a modified Rodnan Skin Score of at least 20 (maximum score 51) in the absence of trunk involvement or a modified Rodnan Skin Score of at least 16 in patients with trunk involvement Female patients of child bearing potential must be using two acceptable methods of contraception (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through Study Completion. Period abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Male patients must be using a two acceptable methods of contraception, (e.g., spermicidal gel plus condom) for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child in the three (3) months following last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients meeting any of the following criteria will be excluded from entry into or continuation in the study unless sponsor approval is obtained: 1. SSc patients with a MRSS greater than 35. 2. Concurrent connective tissue diseases other than SSc including SSc-like illnesses related to environmental, ingested or injected agents, and also including overlap syndromes and mixed connective tissue disease. 3. Significant pre-existing internal organ damage: kidneys: MDRD calculated creatinine clearance < 40 mL/min renal crisis (acute onset of renal failure, moderate to marked hypertension, and normal urine sediment with mild proteinuria) in the 2 months prior to treatment lungs: FVC < 50% predicted CO diffusion capacity < 40% predicted heart: left ventricular ejection fraction < 40% ECG conduction abnormalities deemed by the Investigator to be clinically significant (including atrio-ventricular blocks, atrial or ventricular arrhythmias, sinus pauses > 3 seconds) gut: pseudo-obstruction mal-absorption requiring parental nutrition. 4. Existing myositis: serum creatine phosphokinase > 3 fold of the upper-limit 5. Conditions that might mimic potential side effects of STI571: hematological conditions: - thrombocytopenia < 100 x 109/L neutropenia < 1.5 x 109/L moderate hepatic insufficiency with transaminase levels >3 fold the upper limit of normal, or bilirubin > 2 fold the upper limit of normal PLS SEE PROTOCOL

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of oral STI571 in skin fibrosis in systemic sclerosis (SSc) patients as measured by an improvement in the modified Rodnan Skin Score. To assess the safety and tolerability of oral STI571 in SSc patients.;Secondary Objective: To assess improvement in lung functions as measured by CO diffusion capacity (DLCO) and Forced Vital Capacity (FVC). To assess biomarkers reflecting the direct effects of STI571 on its biological targets. To determine the PK trough levels of STI571 and its major active metabolite CGP74588 during dose escalation and the maintenance phase of the study.;Primary end point(s): To assess the efficacy of oral STI571 in skin fibrosis in systemic sclerosis (SSc) patients as measured by an improvement in the modified Rodnan Skin Score (MRSS) To assess the safety and tolerability of oral STI571 in SSc patients

Secondary Outcome Measures

Name	Time	Method

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