Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

Tracking Information
First Submitted Date ICMJE	October 1, 2008
First Posted Date ICMJE	October 2, 2008
Results First Submitted Date	January 30, 2012
Results First Posted Date	February 29, 2012
Last Update Posted Date	February 29, 2012
Study Start Date ICMJE	January 2009
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 30, 2012)	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 ]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 ]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 ]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 ]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.
Original Primary Outcome Measures ICMJE; (submitted: October 1, 2008)	Incidence of pleural or pericardial effusions [ Time Frame: Continuously ]
Change History	Complete list of historical versions of study NCT00764309 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis
Official Title ICMJE	An Open Label Study to Evaluate the Safety of Dasatinib in the Treatment of Scleroderma Pulmonary Interstitial Fibrosis
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 Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Scleroderma
Intervention ICMJE	Drug: dasatinib; Tablets, Oral, 100 mg, once daily, 6 months; Other Names: Sprycel; BMS 354825
Study Arms	Experimental: A1; Intervention: Drug: dasatinib
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 30, 2012)	47
Original Estimated Enrollment ICMJE; (submitted: October 1, 2008)	30
Actual Study Completion Date	April 2011
Actual Primary Completion Date	June 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00764309
Other Study ID Numbers ICMJE	CA180-267
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Bristol-Myers Squibb
Study Sponsor ICMJE	Bristol-Myers Squibb
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account	Bristol-Myers Squibb
Verification Date	January 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP