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

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ClinicalTrials.gov Identifier: NCT03439514
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : June 5, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Dilated Cardiomyopathy Lamin A/C Gene Mutation Drug: ARRY-371797 Other: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
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.
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.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : December 12, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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)


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

Secondary Outcome Measures :
  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 ]
    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.

  3. Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) as measured by Total Symptom Score (TSS) domain [ Time Frame: at Weeks 12 and 24 ]
    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.

  4. 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 ]
    Measured by the scale of: none, mild, moderate, severe or very severe (listed from better to worse)

  5. 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 ]
    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).

  6. Change from baseline in N-terminal pro-brain natriuretic peptide (NT-proBNP) [ Time Frame: at Weeks 4, 12 and 24 ]
  7. 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 ]
  8. Hospitalization-free survival (HFS) [ Time Frame: From randomization up to 24 months ]
    Defined as the time from randomization until the earliest of hospitalization for heart-failure related reasons or death due to any cause.

  9. Overall survival (OS) [ Time Frame: From randomization up to 24 months ]
    Defined as the time from randomization until death due to any cause.

  10. Number of participants with Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (SAEs) [ Time Frame: From randomization until approximately 18 months ]
    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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 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., 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439514


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

Locations
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Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03439514    
Other Study ID Numbers: ARRAY-797-301
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: June 5, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
cardiomyopathy
Lamin Type A
heart failure
ARRY-797
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly