Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00764309
First received: October 1, 2008
Last updated: January 30, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Scleroderma
Drug: dasatinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Evaluate the Safety of Dasatinib in the Treatment of Scleroderma Pulmonary Interstitial Fibrosis

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.

  • Reasons for Discontinuation of Study Treatment [ Time Frame: 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 ] [ Designated as safety issue: Yes ]

    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.


  • Laboratory Test Results Summary of Toxicity: Hematology [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.

  • Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR) [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 47
Study Start Date: January 2009
Study Completion Date: April 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1 Drug: dasatinib
Tablets, Oral, 100 mg, once daily, 6 months
Other Names:
  • Sprycel
  • BMS 354825

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00764309

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
United States, California
Ucla Division Of Rheumatology
Los Angeles, California, United States, 90095
United States, Connecticut
University Of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, District of Columbia
Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Illinois
Northwestern University Feinberg School Of Medicine
Chicago, Illinois, United States, 60611
United States, Massachusetts
Boston University School Of Medicine
Boston, Massachusetts, United States, 02118
United States, Michigan
University Of Michigan
Ann Arbor, Michigan, United States, 48106
West Michigan Rheumatology
Grand Rapids, Michigan, United States, 49546
United States, New Jersey
Umdnj Clinical Research Center
New Brunswick, New Jersey, United States, 08903
United States, New York
Hospital For Special Surgery
New York, New York, United States, 10021
United States, Pennsylvania
University Of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02905
United States, South Carolina
Medical University Of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00764309     History of Changes
Other Study ID Numbers: CA180-267
Study First Received: October 1, 2008
Results First Received: January 30, 2012
Last Updated: January 30, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Fibrosis
Pulmonary Fibrosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Dasatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014