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A Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT02057341
First received: February 5, 2014
Last updated: June 1, 2016
Last verified: June 2016
  Purpose
This is a Phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug ARRY-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin A/C gene mutation, and to further evaluate the drug's safety. Approximately 12 patients from the US will be enrolled in this study.

Condition Intervention Phase
LMNA-Related Dilated Cardiomyopathy
Drug: ARRY-371797, p38 inhibitor; oral
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test. [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Assess the efficacy of study drug in terms of left ventricular function. [ Time Frame: 48 weeks ]
  • Assess the efficacy of study drug in terms of right ventricular function. [ Time Frame: 48 weeks ]
  • Assess the safety of study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. [ Time Frame: 48 weeks ]
  • Characterize the pharmacokinetics (PK) of study drug and metabolites in terms of plasma concentration-time profiles and model-based PK parameters. [ Time Frame: 48 weeks ]

Enrollment: 12
Study Start Date: February 2014
Study Completion Date: May 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARRY-371797 (Dose 1) Drug: ARRY-371797, p38 inhibitor; oral
multiple dose, single schedule
Experimental: ARRY-371797 (Dose 2) Drug: ARRY-371797, p38 inhibitor; oral
multiple dose, single schedule

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Patients with idiopathic dilated cardiomyopathy and stable New York Heart Association (NYHA) Class II - IIIa congestive heart failure (CHF).
  • Stable, guidelines-based medical and device therapy, without any CHF hospitalizations or change in heart failure drug dose with ≥ 50% reduction in dose or ≥ 100% increase in dose in the past 3 months.
  • Left ventricular (LV) end diastolic diameter by trans-thoracic echocardiography of > 3.3 cm/m2 (for females) or 3.4 cm/m2 (for males) and/or LV ejection fraction ≤ 45%.
  • Gene positive for a pathogenic mutation in the LMNA gene, as determined by a CLIA-certified clinical laboratory (mutations including but not limited to: splice-site, non-sense, deletion mutations, a mis-sense mutation in a highly conserved codon, a mis-sense mutation involving a major charge change, a mis-sense mutation previously associated with genetic dilated cardiomyopathy).
  • Within 3 weeks prior to first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 350 m AND/OR ≥ 100 m and ≤ 450 m AND ≤ 60% predicted distance AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
  • On the day before and day of first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 400 m (with the greater value within 10% of the lesser value) AND/OR ≥ 100 m and ≤ 475 m (with the greater value within 10% of the lesser value) AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
  • Acceptable hematology, hepatic and renal function laboratory values within 3 weeks prior to first dose of study drug.
  • Additional criteria exist.

Key Exclusion Criteria:

  • Unstable clinical cardiac symptoms requiring unscheduled hospitalization within 60 days prior to study start.
  • Clinically significant coronary artery disease, as per Investigator judgment.
  • Currently receiving continuous intravenous (IV) inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation.
  • Any of the following within 60 days prior to study start: Myocardial infarction, cardiac surgical procedures, acute coronary syndrome, hemodynamically destabilizing cardiac arrhythmia, serious systemic infection with evidence of septicemia, any major surgical procedure requiring general anesthesia.
  • Uncorrected, hemodynamically significant primary valvular disease.
  • Initiation of cardiac resynchronization therapy within 180 days prior to study start.
  • Likelihood, in the Investigator's opinion, of undergoing cardiac transplantation, left ventricular assist device or other device implantation, or other cardiac surgery within the next 6 months; or of requiring continuous IV inotropic treatment, or referral for hospice or end-of-life treatment.
  • Active malignancy (except surgically-curative basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma).
  • Receiving chronic immunosuppressant therapy.
  • Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C.
  • Participation in any other investigational study of drugs or devices within 30 days prior to study start.
  • Additional criteria exist.
  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: NCT02057341

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Colorado
University of Colorado School of Medicine
Aurora, Colorado, United States, 80045
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Wisconsin
Meriter Wisconsin Heart
Madison, Wisconsin, United States, 53713
Sponsors and Collaborators
Array BioPharma
  More Information

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT02057341     History of Changes
Other Study ID Numbers: ARRAY-797-231 
Study First Received: February 5, 2014
Last Updated: June 1, 2016

Keywords provided by Array BioPharma:
laminopathy

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly

ClinicalTrials.gov processed this record on February 24, 2017