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

Título: 
A Study of ARRY-371797 in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
Estado de reclutamiento: 
Recruiting
Estado se actualizó más recientemente: 
January 2, 2020
Fenotipo(s) clínico(s): 
LMNA Related Disorders
Gene(s): 
LMNA
Propósito de estudio: 

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.

Intervención / tratamiento: 
Drug: ARRY-371797
Fase: 
Phase 3
Descripción del estudio: 

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.

Tipo de estudio: 
Interventional
Título oficial: 
A Phase 3, Multinational, Randomized, Placebo-Controlled Study of ARRY-371797 in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
Fecha de inicio del estudio: 
March 12, 2018
Fecha de finalización del estudio: 
July 2020
Objetivo(s) principal(es): 

Change from baseline in 6-minute walk test (6MWT) [ Time Frame: at Week 12 ]

Objetivo(s) secundario(s): 
  1. Change from baseline in 6-minute walk test (6MWT) [ Time Frame: at Weeks 4 and 24 ]
  2. Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) domain [ Time Frame: at Weeks 12 and 24 ]
  3. The KCCQ is a self-administered questionnaire that requires 4 to 6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). The PL is a single domain consisting of 7 items scored using a range of 0 - 100, in which higher scores reflect better physical functioning status.
  4. Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) as measured by Total Symptom Score (TSS) domain [ Time Frame: at Weeks 12 and 24 ]
  5. The KCCQ is a self-administered questionnaire that requires 4 to 6 minutes to complete. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and Quality of Life (QoL). The TSS is a combined score based upon the symptom burden, symptom frequency and symptom severity domains of the questionnaire. Scores are transformed to a range of 0 - 100, in which higher scores reflect better health status.
  6. Change from baseline in Patient Global Impression score of Severity(PGI-S) of heart failure symptoms and physical activity limitations [ Time Frame: at Weeks 12 and 24 ]
  7. Measured by the scale of: none, mild, moderate, severe or very severe (listed from better to worse)
  8. Change from baseline in Patient Global Impression score of Change (PGI-C) in heart failure symptoms and physical activity limitations [ Time Frame: at Weeks 12 and 24 ]
  9. Measured by the scale of: very much better, moderately better, a little better, no change, a little worse, moderately worse, very much worse (listed from better to worse).
  10. Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: at Weeks 4, 12 and 24 ]
  11. Plasma concentrations of ARRY-371797 and metabolites predose and at a single time point post dose on specified visit days [ Time Frame: Duration of treatment cycle, 24 weeks ]
  12. Hospitalization-free survival (HFS) [ Time Frame: From randomization up to 24 months ]
  13. Defined as the time from randomization until the earliest of hospitalization for heart-failure related reasons or death due to any cause.
  14. Overall survival (OS) [ Time Frame: From randomization up to 24 months ]
  15. Defined as the time from randomization until death due to any cause.
  16. Number of participants with Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (SAEs) [ Time Frame: From randomization until approximately 18 months ]
  17. Severity of AEs will be graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (April 2005), as appropriate
Elegibilidad: 

Ages Eligible for Study: 18 Years and older   (Adult, Older Adult)

Sexes Eligible for Study: All

Accepts Healthy Volunteers: No

Criterios de inclusión: 
  • 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
Criterio de exclusión: 
  • 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.
Sitio(s) de estudio / Ubicacion(es): 

Multiple study sites in the United States, Argentina, Belgium, Canada, Italy, Mexico, Netherlands, Spain and the United Kingdom. Contact Array BioPharma for more information on study sites near you. 

Patrocinadores y Colaboradores: 

Array BioPharma

Investigador(es) principal(es): 

Study Director:

Array BioPharma, Inc

Para obtener más información, por favor comuníquese con el Coordinador del estudio: 

Contact:  

Email: 

Phone: 

ID de ClinicalTrials.gov: 
NCT03439514