Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

Scleroderma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00764309
• Other study ID #: CA180-267
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 1, 2008
• Last updated: January 30, 2012
• Start date: January 2009
• Est. completion date: April 2011

Study information

• Verified date: January 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: April 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

Drug:
• dasatinib
Tablets, Oral, 100 mg, once daily, 6 months

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes
Primary	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	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form