A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation

NCT03439514 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: ARRAY-797-301C44110022017-004310-25
• Study Type: interventional
• Target: 77
• Locations: 10 countries
• Sites: 107

Brief Summary

This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). The study will further evaluate a dose level of study drug (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.

Conditions

Dilated Cardiomyopathy; Lamin A/C Gene Mutation

Keywords

cardiomyopathy; Lamin Type A; heart failure; ARRY-797; C4411002

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24

  The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. Study discontinuation \& death were incorporated into endpoint definition through ranking in hypothesis testing of treatment difference. Missing data resulting from study discontinuation were imputed using control-based multiple imputation method to estimate treatment effect.

  Baseline, Week 24

Secondary Outcomes (12)

• Change From Baseline in 6 MWT at Weeks 4 and 12

  Baseline, Week 4, Week 12

• Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24

  Baseline, Week 12, Week 24

• Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24

  Week 12, Week 24

• Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24

  Week 12, Week 24

• Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24

  Baseline, Week 4, Week 12, Week 24

Study Arms (2)

Part 1 Double-blind Treatment

EXPERIMENTAL

ARRY-371797 (PF-07265803) tablet orally OR matching placebo tablet orally

Drug: ARRY-371797 (PF-07265803); Other: Placebo

Part 2 Open-label Treatment

EXPERIMENTAL

ARRY-371797 (PF-07265803) tablet orally

Drug: ARRY-371797 (PF-07265803)

Interventions

ARRY-371797 (PF-07265803) DRUG

400 mg twice daily (BID)

Part 1 Double-blind Treatment; Part 2 Open-label Treatment

Placebo OTHER

BID

Part 1 Double-blind Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as:
• Gene positive for a pathogenic, likely pathogenic, or VUS mutation in the LMNA gene as determined by an accredited clinical laboratory.
• Evidence of cardiac impairment in 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 treatment or CRT-D initiated at least 6 months prior to initiation of study treatment and defibrillation function activated at least 4 weeks 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); a. Screening: 6MWT distance \>100 m but ≤450 m, AND b. Day -1 visit: 6MWT distance \>100 m but ≤485 m, AND c. Baseline visit (Day 1): 6MWT distance \>100 m but ≤485
• Class II/III patients must be stable for at least 3 months
• Stable medical and/or device therapy consistent with regional American Heart Association (AHA) / American College of Cardiology (ACC) or European Society of Cardiology (ESC) guidelines at the investigator discretion, without change in heart failure drug(s) dose in the past 1 month.
• Patients must meet acceptable hematology, hepatic and renal laboratory values within 35 days prior to Day 1 as specified in the protocol.

You may not qualify if:

• 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 intermittent or continuous IV inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation. Participants listed for cardiac transplantation may be enrolled provided transplantation is not likely to occur in the next 6 months.
• Myocardial infarction, cardiac surgical procedures (other than for pacemaker/ICD/CRT-D implantation or replacement), acute coronary syndrome, serious systemic infection with evidence of septicemia, or any major surgical procedure requiring general anesthesia within 3 months prior to screening.
• Currently receiving or deemed at high risk of requiring chronic renal replacement therapy (eg, hemodialysis or peritoneal dialysis) within 6 months.
• Initiation of CRT within 6 months prior to screening.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (107)

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham the Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

IDS Pharmacy at UAB Hospital

Birmingham, Alabama, 35249, United States

Location

Cardiovascular Clinical Trials Unit

Birmingham, Alabama, 35294, United States

Location

CB Flock Research Corporation

Mobile, Alabama, 36608, United States

Location

Chandler Regional Medical Center

Chandler, Arizona, 85224, United States

Location

Valley Heart Rhythm Specialists, PLLC

Chandler, Arizona, 85224, United States

Location

Cardiovascular and Stem Cell Consultants

Gilbert, Arizona, 85297-0425, United States

Location

Cardiovascular Research Clinic

Gilbert, Arizona, 85297-0425, United States

Location

Dignity Health, Mercy Gilbert Medical Center

Gilbert, Arizona, 85297-0425, United States

Location

Mercy Gilbert Medical Center

Gilbert, Arizona, 85297, United States

Location

Children's Clinic

Tucson, Arizona, 85712, United States

Location

Banner - Banner University Medical Center South

Tucson, Arizona, 85713, United States

Location

Banner - University Medical Center Tucson

Tucson, Arizona, 85719, United States

Location

Banner University Medicine North

Tucson, Arizona, 85719, United States

Location

Banner University Medical Center Tuscon

Tucson, Arizona, 85724, United States

Location

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724, United States

Location

Ahmanson Cardiomyopathy Center Cardiovascular Genetics

Los Angeles, California, 90095, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Colorado Academic Offices Building

Aurora, Colorado, 80045, United States

Location

University of Colorado Clinical and Translational Research Center

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

University of South Florida

Tampa, Florida, 33606-3601, United States

Location

USF Health

Tampa, Florida, 33606, United States

Location

Florida Cardiovascular Institute PA

Tampa, Florida, 33609, United States

Location

Centers for Heart Failure Therapy

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Columbus Cardiology Associates Research - Centricity Research - HyperCore - PPDS

Columbus, Georgia, 31904-6877, United States

Location

Columbus Cardiology Associates Research - IACT - HyperCore - PPDS

Columbus, Georgia, 31904-6877, United States

Location

Columbus Regional Research Institute at Talbotton - Centricity Research - HyperCore - PPDS

Columbus, Georgia, 31904-8946, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Saint Luke's Idaho Cardiology Associates

Boise, Idaho, 83712-6246, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MyMichigan Medical Center Midland

Midland, Michigan, 48670, United States

Location

Washington University Center For Advanced Medicine

St Louis, Missouri, 63110, United States

Location

Washington University Center for Outpatient Health

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Rutgers New Jersey Medical School - Doctors Office Center

Newark, New Jersey, 07103, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

NYU School of Medicine / NYU Langone Health

New York, New York, 10016, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Columbia University/Presbyterian Hospital - Vivian & Seymour Milstein Family Heart Center

New York, New York, 10032, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425-8911, United States

Location

Medical University of South Carolina - PPDS

Charleston, South Carolina, 29425, United States

Location

Stern Cardiovascular Foundation Inc

Germantown, Tennessee, 38138, United States

Location

Tennessee Center for Clinical Trials

Tullahoma, Tennessee, 37388, United States

Location

Baylor Scott and White Heart and Vascular Hospital

Dallas, Texas, 75226, United States

Location

Baylor Annette C and Harold C Simmons Transplant Institute

Dallas, Texas, 75246, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Meriter Hospital

Madison, Wisconsin, 53713, United States

Location

Fundacion Favaloro para la Docencia e Investigacion Medica

Buenos Aires, Buenos Aires F.D., C1093AAS, Argentina

Location

Instituto CAICI

Rosario, Santa Fe Province, S2000 PBJ, Argentina

Location

Hospital Provincial Del Centenario

Rosario, Santa Fe Province, S2000KDS, Argentina

Location

Hospital Británico de Buenos Aires

Buenos Aires, C1280AEB, Argentina

Location

Hospital Provincial Dr Jose Maria Cullen

Santa Fe, S3000EOZ, Argentina

Location

Onze-Lieve-Vrouwziekenhuis

Aalst, Oost-vlaanderen, 9300, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Nova Scotia Health Authority (Capital District Health Authority)

Halifax, Nova Scotia, B3H 1V7, Canada

Location

NSHA QEII Health Sciences Halifax Infirmary

Halifax, Nova Scotia, B3H 3A7, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Kawartha Cardiology Clinical Trials

Peterborough, Ontario, K9J 0B2, Canada

Location

Clinical Laboratories of Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Centre Intégré Universitaire de santé et de services sociaux de l'Estrie Centre hospitalier

Sherbrooke, Quebec, J1G 2E8, Canada

Location

Ospedale Di Cattinara

Trieste, Friuli Venezia Giulia, 34149, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, 00189, Italy

Location

Ospedale Santa Maria Della Misericordia Perugia

Perugia - Località S. Andrea Delle Fratte, Perugia, 6132, Italy

Location

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, PV, 27100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

Lacopo Olivotto, Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

Location

A.O.U. di Perugia Ospedale Santa Maria della Misericordia

Perugia, Umbria, 06156, Italy

Location

AO Ospedale Policlinico Consorziale di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Pavia - Istituti Clinici Scientifici Maugeri Spa ? Società Benefit

Pavia, 27100, Italy

Location

A.O.U. di Perugia Ospedale Santa Maria Della Misericordia

Perugia, 06132, Italy

Location

A.O.U. di Perugia Ospedale Santa Maria della Misericordia

Perugia, 06156, Italy

Location

Presidio Ospedaliero Madonna del Soccorso

San Benedetto del Tronto, 63074, Italy

Location

Ospedale Di Cattinara

Trieste, 34149, Italy

Location

Hospital Boutique Riobamba

Mexico City, Mexico City, 07300, Mexico

Location

Cardiolink Clin Trials S.C.

Monterrey, Nuevo León, 64060, Mexico

Location

Christus Muguerza Hospital Alta Especialidad

Monterrey, Nuevo León, 64060, Mexico

Location

Fundación de Atención e Investigación Médica Lindavista S.C.

Mexico City, 07300, Mexico

Location

Amsterdam UMC, Location Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Sykehuset Innlandet HF Hamar

Hamar, 2318, Norway

Location

Oslo University Hospital, Rikshospitalet

Oslo, 0424, Norway

Location

Centro de Farmacovigilancia de Galicia

Santiago de Compostela, A Coruña, 15781, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Complejo Hospitalario Universitario de Vigo - H. Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, 14004, Spain

Location

Hospital General Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, 28222, Spain

Location

Hospital Universitario Son Llatzer

Palma de Mallorca, 07198, Spain

Location

Queen Elizabeth University Hospital - PPDS

Glasgow, Glasgow CITY, G51 4TF, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (4)

• Garcia-Pavia P, Lakdawala NK, Sinagra G, Ripoll-Vera T, Afshar K, Priori SG, Ware JS, Owens A, Li H, Angeli FS, Elliott P, MacRae CA, Judge DP. Characterization and natural history of patients with LMNA-related dilated cardiomyopathy in the phase 3 REALM-DCM trial. ESC Heart Fail. 2024 Dec;11(6):4201-4208. doi: 10.1002/ehf2.14955. Epub 2024 Aug 15.

  PMID: 39145700 DERIVED

• Garcia-Pavia P, Palomares JFR, Sinagra G, Barriales-Villa R, Lakdawala NK, Gottlieb RL, Goldberg RI, Elliott P, Lee P, Li H, Angeli FS, Judge DP, MacRae CA; REALM-DCM Investigators. REALM-DCM: A Phase 3, Multinational, Randomized, Placebo-Controlled Trial of ARRY-371797 in Patients With Symptomatic LMNA-Related Dilated Cardiomyopathy. Circ Heart Fail. 2024 Jul;17(7):e011548. doi: 10.1161/CIRCHEARTFAILURE.123.011548. Epub 2024 Jul 9.

  PMID: 38979608 DERIVED

• Judge DP, Taylor MR, Li H, Oliver C, Angeli FS, Lee PA, MacRae CA. Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary. Future Cardiol. 2023 Mar;19(3):117-126. doi: 10.2217/fca-2022-0125. Epub 2023 Apr 3.

  PMID: 37010012 DERIVED

• MacRae CA, Taylor MR, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene. Future Cardiol. 2023 Feb;19(2):55-63. doi: 10.2217/fca-2022-0099. Epub 2023 Jan 31.

  PMID: 36718638 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Cardiomyopathies; Limb-girdle muscular dystrophy, type 1B; Heart Failure

Interventions

ARRY-371797

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in 2 parts: a randomized, double-blind treatment period for at least 24 weeks, followed by an ARRY-371797 (PF-07265803) open-label treatment period.

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 20, 2018
• Study Start: April 17, 2018
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

CA (7); ES (11); ME (4); BE (2); AR (5); NL (1); US (56); NO (2); IT (16); GB (3)