Clinical trial NCT00764309: Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis
Official title: An Open Label Study to Evaluate the Safety of Dasatinib in the Treatment of Scleroderma Pulmonary Interstitial Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Scleroderma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-10-02
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
timeFrame: 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
measure: Reasons for Discontinuation of Study Treatment
timeFrame: 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
measure: Laboratory Test Results Summary of Toxicity: Hematology
timeFrame: 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
measure: Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Ucla Division Of Rheumatology
state: California
city: Farmington
country: United States
facility: University Of Connecticut Health Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Chicago
country: United States
facility: Northwestern University Feinberg School Of Medicine
state: Illinois
city: Boston
country: United States
facility: Boston University School Of Medicine
state: Massachusetts
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: West Michigan Rheumatology
state: Michigan
city: New Brunswick
country: United States
facility: Umdnj Clinical Research Center
state: New Jersey
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: Pittsburgh
country: United States
facility: University Of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University Of South Carolina
state: South Carolina
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Martyanov V, Kim GJ, Hayes W, Du S, Ganguly BJ, Sy O, Lee SK, Bogatkevich GS, Schieven GL, Schiopu E, Marangoni RG, Goldin J, Whitfield ML, Varga J. Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease. PLoS One. 2017 Nov 9;12(11):e0187580. doi: 10.1371/journal.pone.0187580. eCollection 2017.