Dilated Cardiomyopathy (DCM) with Lamin A/C gene (LMNA) Mutation MedDRA version: 20.0 Level: LLT Classification code 10056419 Term: Dilated cardiomyopathy System Organ Class: 100000004849
Conditions
Interventions
Product Name: ARRY-371797
Product Code: ARRY-371797
Pharmaceutical Form: Film-coated tablet
CAS Number: 765914-60-1
Current Sponsor code: ARRY-371797
Concentration unit: mg milligram(s)
Concentration
Sponsors
Array BioPharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Selected Key Inclusion Criteria: • Provide a signed and dated informed consent document prior to initiation of any study-related procedures. Patients under guardianship or partial guardianship will be eligible unless prohibited by local laws or by local/central ethic committees • Age = 18 years at time of informed consent • Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as: o 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 o Evidence of cardiac impairment as determined by EF = 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 • 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 within 35 days prior Day 1 • Affiliated to a social security system, or is a beneficiary (if applicable in the national regulation) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Selected Key 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., moderatesevere) 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 35 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. • Pregnancy or breastfeeding, or patients who plan to become pregnant during the duration of the trial • Patients with an underlying condition that may impact the ability of the 6MWT to reflect changes in cardiovascular function such as: an orthopedic condition that limits walking abilities (e.g., severe arthritis), significant musculoskeletal pathology, significant chronic obstructive pulmonary disease (COPD) that limits exercise tolerance or any other condition that according to the Investigator's assessment significantly limits a patient's performance on the 6MWT independently from the patient's cardiomyopathy. • Documented hypersensitivity/allergy or clinically significant intolerance to any component of drug product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: NYHA Class II/III patients only: Evaluate the effect of ARRY-371797 on functional capacity (as measured by the 6-minute walk test [6MWT]) compared to placebo;Secondary Objective: - NYHA Class II/III patients only: Evaluate additional measures of efficacy of ARRY-371797 compared to placebo in the randomized period - Characterize the plasma pharmacokinetics (PK) of ARRY-371797 and metabolites - Evaluate the impact of ARRY-371797 on hospitalization-free survival (HFS) and overall survival (OS) - Evaluate the safety of ARRY-371797 compared to placebo;Primary end point(s): NYHA Class II/III patients only: Change from baseline in 6MWT at Week 12;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. NYHA Class II/III patients only: Change from baseline in 6MWT at Weeks 4 and 24 2. NYHA Class II/III patients only: Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) domains at Weeks 12 and 24 3. NYHA Class II/III patients only: Change from baseline in Patient Global Impression (PGI) scores at Weeks 12 and 24 - Patient Global Impression of Severity (PGI-S) - Patient Global Impression of Change (PGI-C) 4. NYHA Class II/III patients only: Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) at Weeks 4, 12 and 24 5. Plasma concentrations of ARRY-371797 and metabolites (AR00420643, AR00428028 and AR00486705) predose and at a single time point postdose on specified visit days 6. HFS: Defined as the time from randomization to heart failure (HF) - related hospitalization or death due to any cause 7. OS 8. Safety as determined by: - Incidence and severity of adverse events (AEs) - Changes in clinical safety laboratory tests, vital signs and 12-lead electrocardiograms (ECGs) - Incidence and severity of ventricular or atrial arrhythmias detected clinically using existing implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) or other applicable device interrogations at Weeks 12 and 24, if applicable;Timepoint(s) of evaluation of this end point: 1. Weeks 4 and 24 2. Weeks 12 and 24 3. Weeks 12 and 24 4. Weeks 4, 12 and 24 5. Predose and at a single time point postdose on specified visit days 6. Throughout the duration of the study 7. Throughout the duration of the study 8. Safety endpoints throughout the duration of the study | — |
Countries
Argentina, Belgium, Canada, Denmark, France, Germany, Italy, Mexico, Netherlands, Norway, Spain, United Kingdom, United States
Contacts
Public ContactTeri Whisenand
Array BioPharma Inc.
Outcome results
None listed