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: PF-07265803
Pharmaceutical Form: Film-coated tablet
CAS Number: 765914-60-1
Current Sponsor code: ARRY-371797
Other descriptive name: PF-07265803
Concentration
Sponsors
Array BioPharma Inc. (a wholly owned subsidiary of Pfizer 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: a) Gene positive for a pathogenic, likely pathogenic or VUS mutation in the LMNA gene as determined by an accredited clinical laboratory; b) NYHA functional Class II or III that has been stable for at least 3 months; c) Evidence of cardiac impairment as determined by 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 intervention or CRT-D initiated at least 6 months prior to initiation of study intervention and defibrillation function activated at least 4 weeks prior to initiation of study intervention. Devices must have activated pacing capabilities or a separate pacemaker must be present. • 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 regional (e.g. American Heart Association (AHA)/American College of Cardiology (ACC) or European Society of Cardiology (ESC) guidelines at the investigator discretion, without change in HF drug(s) dose in the past 1 month. • Patients must meet acceptable hematology, hepatic and renal laboratory values as specified within 35 days prior Day 1 Please refer to Protocol, section 5.1 for detailed list of Inclusion Criteria. 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 (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 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. • 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. • 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. Please refer to Protocol, section 5.2 for detailed list of Exclusion Criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effect of ARRY-371797 (PF-07265803) on functional capacity (as measured by the 6-minute walk test [6MWT]) compared to placebo;Secondary Objective: - Evaluate additional measures of efficacy of ARRY-371797 (PF-07265803) compared to placebo in the randomized period. - Evaluate the impact of ARRY-371797 (PF-07265803) on composite of all-cause mortality, or worsening heart failure (WHF). - Evaluate the impact of ARRY-371797 (PF-07265803) on overall survival (OS). - Evaluate the safety of ARRY-371797 (PF-07265803) compared to placebo.;Primary end point(s): NYHA Class II/III patients only: Change from baseline in 6MWT at Week 24;Timepoint(s) of evaluation of this end point: At week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. NYHA Class II/III patients only: Change from baseline in 6MWT at Weeks 4 and 12 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. Defined as the time from randomization to the first occurrence of any event in the composite of death due to any cause, or worsening heart failure (HF-related hospitalization or HF-related urgent care visit). 6. 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;Timepoint(s) of evaluation of this end point: 1. Weeks 4 and 12 2. Weeks 12 and 24 3. Weeks 12 and 24 4. Weeks 4, 12 and 24 5. Throughout the duration of the study 6. Throughout the duration of the study 7. Safety endpoints throughout the duration of the study | — |
Countries
Argentina, Belgium, Canada, France, Germany, Italy, Mexico, Netherlands, Norway, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed