Efficacy and Tolerability of STI571 (Imatinib Mesylate) for the Treatment of Fibrosis in Participants With Systemic Sclerosis

Study Overview
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Brief Summary
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This study investigates the efficacy and safety of STI571 for the treatment of fibrosis in participants with systemic sclerosis. Other purposes of the study were to investigate whether STI571 is effective in improving lung functions and other test results called biomarkers. Whether STI571 is well-absorbed in systemic sclerosis participants' gut was also investigated by testing the drug level in the blood (pharmacokinetics).

Official Title
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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

Conditions
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Systemic Sclerosis, Scleroderma

Intervention / Treatment
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* Drug: STI571


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants who are equal to or older than 18 years of age and who have early diffuse cutaneous systemic sclerosis (Disease duration < 18 months from the first non-Raynaud's symptom) Participants with a modified Rodnans Skin Score (MRSS) of at least 20 in the absence of trunk involvement or a MRSS of at least 16 in patients with trunk involvement Female patients of childbearing potential practicing two acceptable forms of contraception Exclusion Criteria: SSc patients with a MRSS greater than 35 Concurrent connective tissue diseases other than systemic sclerosis Significant pre-existing heart, liver, lungs, digestive system, blood and other diseases, cancer Conditions that might mimic the potential side effects of STI571 (blood conditions, liver damage, chronic diarrhea, edema) Concurrent medical therapies (or during last 6 weeks before first dosing) that may potentially influence outcome of the study Allergic to the study medication Pregnancy Breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ST1571<br>Participants received ST1571 100 mg tablets, orally, once daily. Initiated at an oral dose of 200 mg/day for 4 weeks then titrated up to 400 mg/day for 2 weeks followed by 600 mg/day until Week 24, if well tolerated. | Drug: STI571<br>* STI571 tablets taken orally once a day<br>* Other names: Gleevec, Glivec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | The efficacy of oral STI571 in participants with systemic sclerosis is defined by an improvement in MRSS. Skin thickness was assessed clinically in each of 17 body areas and scored using a 0-3 scale, where 0= normal, 1= mild thickness, 2= moderate thickness, and 3= severe thickness (maximum score 51). A higher score indicates greater severity of the disease. | Baseline, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS) | 
| Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's) | An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to the study drug. An SAE is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, is medically significant, i.e., defined as an event that jeopardizes the patient or may require medical or surgical intervention to prevent one of the outcomes listed above. | Baseline to Week 48/EOS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | The following MRSS categories were calculated for up to Week 48: Non-response: a reduction in MRSS <25%, Partial response: a reduction in MRSS between 25-<50%, Complete response: a reduction in MRSS between 50-<80%, Remission: a reduction in MRSS ≥80%. | Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic sclerosis, scleroderma, fibrosis, STI571, imatinib