A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation

Not Recruiting

Trial ID: NCT03439514


This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). The study will further evaluate a dose level of study drug (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.

Official Title

A Phase 3, Multinational, Randomized, Placebo-controlled Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation (REALM-DCM)

Stanford Investigator(s)

Matthew Wheeler
Matthew Wheeler

Associate Professor of Medicine (Cardiovascular Medicine)


Selected Key Inclusion Criteria:

   - Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class
   II/III/ or Class IV defined as:

   - Gene positive for a pathogenic, likely pathogenic, or VUS mutation in the LMNA gene as
   determined by an accredited clinical laboratory.

   - Evidence of cardiac impairment in LVEF <= 50%

   - 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 and defibrillation function activated at least 4 weeks 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); a. Screening: 6MWT distance >100 m but ≤450 m,
   AND b. Day -1 visit: 6MWT distance >100 m but ≤485 m, AND c. Baseline visit (Day 1):
   6MWT distance >100 m but ≤485

   - Class II/III patients must be stable for at least 3 months

   - Stable medical and/or device therapy consistent with regional American Heart
   Association (AHA) / American College of Cardiology (ACC) or European Society of
   Cardiology (ESC) guidelines at the investigator discretion, without change in heart
   failure drug(s) dose in the past 1 month.

   - Patients must meet acceptable hematology, hepatic and renal laboratory values within
   35 days prior to Day 1 as specified in the protocol.

Selected Key Exclusion Criteria:

   - Presence of other form(s) of cardiomyopathy contributing to HF (eg, inflammatory or
   infiltrative cardiomyopathy), clinically significant cardiac anatomic abnormality
   (eg,LV aneurysm), clinically significant coronary artery disease (eg, coronary
   revascularization, exercise induced angina) or uncorrected, hemodynamically
   significant (ie, moderate-severe) primary structural valvular disease not due to HF,
   per investigator judgment.

   - Currently receiving intermittent or continuous IV inotrope infusion, or presence of a
   ventricular assist device, or history of prior heart transplantation. Participants
   listed for cardiac transplantation may be enrolled provided transplantation is not
   likely to occur in the next 6 months.

   - Myocardial infarction, cardiac surgical procedures (other than for pacemaker/ICD/CRT-D
   implantation or replacement), acute coronary syndrome, serious systemic infection with
   evidence of septicemia, or any major surgical procedure requiring general anesthesia
   within 3 months prior to screening.

   - Currently receiving or deemed at high risk of requiring chronic renal replacement
   therapy (eg, hemodialysis or peritoneal dialysis) within 6 months.

   - Initiation of CRT within 6 months prior to screening.

   - Treatment with any investigational agent(s) for HF within 35 days prior to Day 1.

   - 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), thyroid cancer, or cervical cancer, or, with prior review by the medical
   monitor, other early stage surgically curatively resected malignancies with less than
   a 20% expected 2 year recurrence rate.

   - 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.


other: Placebo

drug: ARRY-371797 (PF-07265803)

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jennifer Marino