Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the safety of Dasatininb in the treatment of scleroderma pulmonary interstitial fibrosis.

Official Title
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An Open Label Study to Evaluate the Safety of Dasatinib in the Treatment of Scleroderma Pulmonary Interstitial Fibrosis

Conditions
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Scleroderma

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Target Population meet American College of Rheumatology (ACR) criteria for scleroderma have clinical evidence of active skin disease with a skin score of ≥15 have had the onset of their first non-Raynaud phenomenon feature of SSc no more than 3 years prior to screening have evidence of fibrosing alveolitis (active pulmonary fibrosis) manifested by a forced vital capacity (FVC) between 45% and 80% of predicted normal and/or diffusing capacity (DLCO) between 30% and 70% of predicted normal values have an abnormal high resolution Computed tomography (CT) scan of the chest/lungs demonstrating typical ground glass changes of alveolitis with background fibrosis have adequate renal function- no evidence of renal crisis in the 2 months prior to enrollment and serum creatinine < 3 mg/dL for both sexes, must use an acceptable form of birth control age ≥ 18 Exclusion Criteria: Clinically significant pleural or pericardial effusion in the previous 12 months: Grade 3 or 4. Patients with recent Grade I or II effusions or peripheral edema will be permitted to enter the study Clinically significant cardiac disease (New York Heart Association Class III or IV) including preexisting arrhythmia, (such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes), myocardial infarction, uncontrolled angina within 6 months, congestive heart failure, cardiomyopathy, or pericardial disease Clinically-significant coagulation or platelet function disorder (eg, known von Willebrand's disease) Abnormal QTcF interval prolonged (> 450 msec) after electrolytes have been corrected on baseline electrocardiogram Laboratory Test Findings Hgb < 10 g/dL; platelet count < 100,000/dL; WBC < 3,000/dL; PMN < 1,000/dL; OR lymphocytes < 350/dL The presence of any of the following laboratory findings at screening: positive for antibodies to hepatitis C virus; positive for antibodies to hepatitis B surface antigen (HBsAg); serum bilirubin 2 times normal, Alanine Aminotransferase (ALT), or Aspartate Aminotransferase (AST)> 2.5 times upper limit of normal Prohibited Treatments and/or Therapies use of other immunosuppressive therapies must be discontinued at enrollment, eg methotrexate, azathioprine, cyclophosphamide, mycophenolic acid, mycophenolate mofetil, cyclosporine treatment with any other experimental or investigational drug(s) concurrently or less than 12 weeks prior to study enrollment use of anti-fibrotic agents must be discontinued at enrollment, eg colchicine, D-penicillamine, minocycline or Type 1 oral collagen

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: A1<br> | Drug: dasatinib<br>* Tablets, Oral, 100 mg, once daily, 6 months<br>* Other names: BMS 354825;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs) | AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded. | From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years | 
| Reasons for Discontinuation of Study Treatment | Participants who discontinued the study due to any AEs were recorded. Significant drug-related discontinuations were those SAEs recorded on the SAE case report forms with relationship to study drug of related or missing and action taken regarding study drug of discontinued or missing. | From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years | 
| Laboratory Test Results Summary of Toxicity: Hematology | Toxicity was graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. (Grade (GR)0=normal, GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening). Granulocyte count (x 10^9 /L), GR1: ≥1.0 - <1.5, GR2: ≥0.5 - <1.0; Hemoglobin (g/dL), GR0: 13-17, GR1: <13 - 10.0 , GR2: 8.0 - <10.0, GR3: 6.5 - <8.0; Platelet count (x 10^9 /L) GR0: 150-400, GR2: ≥50.0 - <75.0; Leukocyte count (x 10^9 /L ), GR0: 3.5-11.1, GR2: 2.0 - <3.0. | From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years | 
| Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR) | GR0=normal,1=mild,2=moderate,3=severe,4=life-threatening. ALP(U/L) GR0:40-135,GR1:>135-337; ALT(U/L) GR0:0-47,GR1:>47-117; AST(U/L) GR0:0-37,GR1:>37-93; High(↑) Calcium(mg/dL) GR0:8.4-10.2,GR1:>10.2-11.5; Low(↓) Calcium(mg/dL) GR0:8.4-10.2,GR1:<8.4-8.0,GR2:7.0-<8.0; CK(U/L) GR0:24-195,GR1:>195-488, GR2:>488-975; Creatinine(mg/dL) GR0:0.6-1.4,GR1:>1.4-2.1,GR2:>2.1-4.2; ↑Potassium(mEq/L) GR0:3.6-5.2,GR1:>5.2-5.5,GR2:>5.5-6.0; ↑Sodium(mEq/L) GR0:134-146; ↓Sodium(mEq/L) GR0:134-146,GR1:<134-130; Inorganic Phosphorus(mg/dL) GR0:2.4-4.9,GR2:≥2.0-<2.5; Total Bilirubin(mg/dL) GR0:0-1.1,GR1:>1.1-2.75. | From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years |