Purpose

This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a gene encoding the lamin A/C protein (LMNA) mutation. The study will further evaluate a dose level of ARRY-371797 that has shown preliminary efficacy and safety in this patient population. After the primary analysis has been performed, eligible patients may receive open-label treatment with ARRY-371797.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as:
  • Gene positive for a deleterious mutation in the LMNA gene as determined by the study central laboratory or by initial laboratory testing (central confirmation of initial laboratory results is required prior to randomization and study treatment).
  • Evidence of cardiac impairment in EF
  • Patient will have an implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D). ICD implanted at least 4 weeks prior to initiation of study treatment or CRT-D initiated at least 6 months prior to initiation of study treatment
  • Class II/III patients must have objective functional impairment evidenced by a reduction in 6-minute walk test (6MWT);
  • Stable medical and/or device therapy consistent with American Heart Association (AHA) / American College of Cardiology (ACC) or European Society of Cardiology (ESC) guidelines
  • Patients must meet acceptable hematology, hepatic and renal laboratory values as specified

Selected

Exclusion Criteria

  • Presence of other form(s) of cardiomyopathy contributing to HF (e.g., inflammatory or infiltrative cardiomyopathy) or clinically significant cardiac anatomic abnormality (e.g., LV aneurysm).
  • Clinically significant coronary artery disease (e.g., coronary revascularization, exercise-induced angina) per Investigator judgment.
  • Uncorrected, hemodynamically significant (i.e., moderate-severe) primary structural valvular disease not due to HF.
  • Currently receiving or deemed at high risk of requiring chronic renal replacement therapy (e.g., hemodialysis or peritoneal dialysis) within 6 months.
  • Treatment with any investigational agent(s) for HF within 28 days prior to Day 1. Any treatment with an investigational agent(s) requires approval from the Medical Monitor.
  • Malignancy that is active or has been diagnosed within 3 years prior to screening, except surgically curatively resected in situ malignancies or surgically cured early breast cancer, prostate cancer, skin cancer (basal cell carcinoma, squamous cell carcinoma) or cervical cancer.
  • Non-cardiac condition that limits lifespan to < 1 year.
  • Serum positive for hepatitis B surface antigen, viremic hepatitis C, or human immunodeficiency virus (HIV) at screening.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
The study will be conducted in 2 parts: a randomized, double-blind treatment period for at least 24 weeks, followed by an ARRY-371797 open-label treatment period.
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
During the randomized, double-blind period, patients, Investigators, site personnel and the sponsor personnel directly involved with the conduct of the study will remain blinded to assigned treatment, except for regulatory reporting requirements.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1 Double-blind Treatment
ARRY-371797 tablet orally OR matching placebo tablet orally
  • Drug: ARRY-371797
    400 mg twice daily (BID)
  • Other: Placebo
    BID
Experimental
Part 2 Open-label Treatment
ARRY-371797 tablet orally
  • Drug: ARRY-371797
    400 mg twice daily (BID)

Recruiting Locations

More Details

Status
Recruiting
Sponsor
Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.