Clinical trial NCT02057341: A Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: LMNA-Related Dilated Cardiomyopathy
Keywords: laminopathy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-02-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test.
timeFrame: 12 weeks
Secondary outcomes:
measure: Assess the efficacy of study drug in terms of left ventricular function.
timeFrame: 48 weeks
measure: Assess the efficacy of study drug in terms of right ventricular function.
timeFrame: 48 weeks
measure: Assess the safety of study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.
timeFrame: 48 weeks
measure: Characterize the pharmacokinetics (PK) of study drug and metabolites in terms of plasma concentration-time profiles and model-based PK parameters.
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Madison
country: United States
facility: Meriter Wisconsin Heart
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: