Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

Phase 1

Completed

Conditions: Scleroderma

Interventions: Drug: dasatinib

Registration Number: NCT00764309

Lead Sponsor: Bristol-Myers Squibb

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
A1	dasatinib	-

Primary Outcome Measures

Name	Time	Method
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)	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	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.
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)	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	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.
Laboratory Test Results Summary of Toxicity: Hematology	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	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.
Reasons for Discontinuation of Study Treatment	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	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (13): Northwestern University Feinberg School Of Medicine
🇺🇸
Chicago, Illinois, United States
Boston University School Of Medicine
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Boston, Massachusetts, United States
Mayo Clinic Arizona
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Scottsdale, Arizona, United States
Ucla Division Of Rheumatology
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Los Angeles, California, United States
University Of Connecticut Health Center
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Farmington, Connecticut, United States
Georgetown University Hospital
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Washington, District of Columbia, United States
West Michigan Rheumatology
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Grand Rapids, Michigan, United States
Umdnj Clinical Research Center
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New Brunswick, New Jersey, United States
Hospital For Special Surgery
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New York, New York, United States
University Of Pittsburgh
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Pittsburgh, Pennsylvania, United States
Medical University Of South Carolina
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Charleston, South Carolina, United States
University Of Michigan
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Ann Arbor, Michigan, United States
Rhode Island Hospital
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Providence, Rhode Island, United States