ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03439514
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : February 4, 2019
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

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 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 : April 2020
Estimated Study Completion Date : July 2020


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)




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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.

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
Contact: Array BioPharma, Inc 303-381-6604 clinicaltrials@arraybiopharma.com

  Hide Study Locations
Locations
United States, Alabama
CB Flock Research Corporation Recruiting
Mobile, Alabama, United States, 36608
Contact: Cheryl Flock    251-725-1014    cflock@cbflockresearch.org   
Principal Investigator: John LeDoux, MD         
United States, Arizona
Mercy Gilbert Medical Center Recruiting
Gilbert, Arizona, United States, 85297
Contact: Brian Mutoff    480-728-8736    brian.mutoff@dignityhealth.org   
Principal Investigator: Nabil Dib, MD         
University of Arizona Sarver Heart Center Recruiting
Tucson, Arizona, United States, 85724
Principal Investigator: Nancy Sweitzer, MD         
United States, California
Ahmanson Cardiomyopathy Center Cardiovascular Genetics Recruiting
Los Angeles, California, United States, 90095
Contact: Eleanor Chang    310-291-6606    elchang@mednet.ucla.edu   
Principal Investigator: Jessica Wang, MD         
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94304
Contact: Jennifer Kim or Brianna Tucker    650-725-6911    bmtucker@stanford.edu/jennckim@stanford.edu   
Principal Investigator: Matthew Wheeler, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Jose Barron    720-848-7090    Jose.Barron@UCDenver.edu   
Principal Investigator: Matthew Taylor, MD         
United States, Florida
Innovative Research of West Florida Recruiting
Clearwater, Florida, United States, 33756
Contact: Tracey Osborn    727-584-6368 ext 201    traceyo@innovativeresearchfl.com   
Principal Investigator: Miguel Trevino, MD         
University of South Florida Recruiting
Tampa, Florida, United States, 33606
Contact: Heather Glunk    813-259-0671    hglunk@health.usf.edu   
Principal Investigator: Thomas McDonald, MD         
United States, Georgia
Columbus Cardiology Associates Research Recruiting
Columbus, Georgia, United States, 31904
Contact: Carla Burton    706-410-1116    cburton@iacthealth.com   
Principal Investigator: Alonzo Jones, MD         
United States, Idaho
Saint Lukes Idaho Cardiology Associates Recruiting
Boise, Idaho, United States, 83712
Principal Investigator: David Hinchman, MD         
United States, Massachusetts
Brigham and Womens Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mary Sheehan    617-732-6237    msheehan1@bwh.harvard.edu   
Principal Investigator: Neal Lakdawala, MD         
United States, Michigan
Mid Michigan Medical Center - Midland Recruiting
Midland, Michigan, United States, 48670
Contact: Jamie Prior    989-631-2469    jamie.prior@midmichigan.org   
Principal Investigator: Jeffrey Martindale, MD         
United States, Missouri
Center For Advanced Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Lisa LaRiccia    314-747-2246    lisa.lariccia@wustl.edu   
Principal Investigator: Gregory Ewald, MD         
United States, New Jersey
Rutgers New Jersey Medical School Recruiting
Newark, New Jersey, United States, 07102
Contact: Khyati Mehta    973-972-6794    mehtakp@njms.rutgers.edu   
Principal Investigator: Marc Klapholz, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Sevinj Sasunova    212-263-4113    sevinj.sasunova@nyumc.org   
Principal Investigator: Stephen Pan, MD         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Andrea Kim    212-305-1368    ak451@cumc.columbia.edu   
Principal Investigator: Farhana Latif, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Theresa Fonk    216-445-1647    fonkt@ccf.org   
Principal Investigator: Wai Hong Wilson Tang, MD         
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Sarah Stockdale    614-292-4084    Sarah.Stockdale@osumc.edu   
Principal Investigator: Ray Hershberger, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jessica Kim    215-615-0497    jessica.kim4@uphs.upenn.edu   
Principal Investigator: Anjali Owens, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Lindsey Stewart    843-792-1238    stew@musc.edu   
Principal Investigator: Dan Judge, MD         
United States, Tennessee
Stern Cardiovascular Foundation Inc Recruiting
Germantown, Tennessee, United States, 38138
Contact: Tammy West    901-271-1000    tammy.west@sterncardio.com   
Principal Investigator: Frank McGrew, MD         
Tennessee Center for Clinical Trials Recruiting
Tullahoma, Tennessee, United States, 36388
Contact: Tammy Davey    931-461-2663    tcctreg@gmail.com   
Principal Investigator: Dinesh Gupta, MD         
United States, Texas
Baylor Scott and White Research Institute Recruiting
Dallas, Texas, United States, 75246
Contact: Amanda Doss    214-865-2419    amanda.doss@bswhealth.org   
Principal Investigator: Robert Gottlieb, MD         
Texas Heart Institute Recruiting
Houston, Texas, United States, 77030
Contact: Gabrielle Phillip    832-355-9614    gphillip@texasheart.org   
Principal Investigator: Emerson Perin, MD         
United States, Wisconsin
Meriter Hospital Recruiting
Madison, Wisconsin, United States, 53713
Contact: Amanda Gessler    608-417-2168    agessler@unitypoint.org   
Principal Investigator: John Moses, MD         
Argentina
Array BioPharma Investigative Site Recruiting
Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina, C1093AAS
Array Investigative Site Recruiting
Buenos Aires, Argentina, C1280AEB
Array Investigative Site Recruiting
Santa Fe, Argentina, S3000EOZ
Belgium
Array BioPharma Investigative Site Recruiting
Aalst, Oost-Vlaanderen, Belgium, 9300
Array BioPharma Investigative Site Recruiting
Leuven, Belgium, 3000
Canada, British Columbia
Array Investigative Site Recruiting
Vancouver, British Columbia, Canada, V6E 1M7
Canada, Nova Scotia
Array BioPharma Investigative Site Recruiting
Halifax, Nova Scotia, Canada, B3H 3A7
Canada, Ontario
Array Investigative Site Recruiting
Peterborough, Ontario, Canada, 02201
Italy
Array Investigative Site Recruiting
San Benedetto Del Tronto, Italy, 63074
Array Investigative Site Recruiting
Trieste, Italy, 34149
Mexico
Array BioPharma Investigative Site Recruiting
Monterrey, Nuevo León, Mexico, 64060
Array BioPharma Investigative Site Recruiting
Ciudad de México, Mexico, 7300
Spain
Array BioPharma Investigative Site Recruiting
Palma De Mallorca, Baleares, Spain, 7198
Array BioPharma Investigative Site Recruiting
Badalona, Cataluña, Spain, 8036
Array Investigative Site Recruiting
Córdoba, Cordoba, Spain, 14004
Array BioPharma Investigative Site Recruiting
Majadahonda, Madrid, Spain, 28222
Array BioPharma Investigative Site Recruiting
Vigo, Pontevedra, Spain, 36312
Array BioPharma Investigative Site Recruiting
A Coruña, Spain, 15006
Array BioPharma Investigative Site Recruiting
Barcelona, Spain, 8035
Array BioPharma Investigative Site Recruiting
El Palmar, Spain, 30120
Array Investigative Site Recruiting
Madrid, Spain, 28007
Sponsors and Collaborators
Array BioPharma
Investigators
Study Director: Study Director Array BioPharma, Inc

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT03439514     History of Changes
Other Study ID Numbers: ARRAY-797-301
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Array BioPharma:
cardiomyopathy
Lamin Type A
heart failure
ARRY-797

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Cardiomegaly