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

• Status: Completed
• Trial end date: 2016-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Array BioPharma; Pfizer

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.