Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis

NCT00764309 | Completed Phase 1 Results

• 1 other identifier: CA180-267
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 13

Brief Summary

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

Conditions

Scleroderma

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (1)

A1

EXPERIMENTAL

Drug: dasatinib

Interventions

dasatinib DRUG

Tablets, Oral, 100 mg, once daily, 6 months

Also known as: Sprycel, BMS 354825

A1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (13)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Ucla Division Of Rheumatology

Los Angeles, California, 90095, United States

Location

University Of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University Feinberg School Of Medicine

Chicago, Illinois, 60611, United States

Location

Boston University School Of Medicine

Boston, Massachusetts, 02118, United States

Location

University Of Michigan

Ann Arbor, Michigan, 48106, United States

Location

West Michigan Rheumatology

Grand Rapids, Michigan, 49546, United States

Location

Umdnj Clinical Research Center

New Brunswick, New Jersey, 08903, United States

Location

Hospital For Special Surgery

New York, New York, 10021, United States

Location

University Of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02905, United States

Location

Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• 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.

  PMID: 29121645 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 2, 2008
• Study Start: January 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: April 1, 2011
• Last Updated: February 29, 2012
• Results First Posted: February 29, 2012

Record last verified: 2012-01

Locations

US (13)