A Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy

NCT02057341 | Completed Phase 2 DMC

• 2 other identifiers: ARRAY-797-231C4411004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug ARRY-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin A/C gene mutation, and to further evaluate the drug's safety. Approximately 12 patients from the US will be enrolled in this study.

Conditions

LMNA-Related Dilated Cardiomyopathy

Keywords

laminopathy

Outcome Measures

Primary Outcomes (1)

• Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test.

  12 weeks

Secondary Outcomes (4)

• Assess the efficacy of study drug in terms of left ventricular function.

  48 weeks

• Assess the efficacy of study drug in terms of right ventricular function.

  48 weeks

• Assess the safety of study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.

  48 weeks

• Characterize the pharmacokinetics (PK) of study drug and metabolites in terms of plasma concentration-time profiles and model-based PK parameters.

  48 weeks

Study Arms (2)

ARRY-371797 (Dose 1)

EXPERIMENTAL

Drug: ARRY-371797, p38 inhibitor; oral

ARRY-371797 (Dose 2)

EXPERIMENTAL

Drug: ARRY-371797, p38 inhibitor; oral

Interventions

ARRY-371797, p38 inhibitor; oral DRUG

multiple dose, single schedule

ARRY-371797 (Dose 1); ARRY-371797 (Dose 2)

Eligibility Criteria

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

You may qualify if:

• Patients with idiopathic dilated cardiomyopathy and stable New York Heart Association (NYHA) Class II - IIIa congestive heart failure (CHF).
• Stable, guidelines-based medical and device therapy, without any CHF hospitalizations or change in heart failure drug dose with ≥ 50% reduction in dose or ≥ 100% increase in dose in the past 3 months.
• Left ventricular (LV) end diastolic diameter by trans-thoracic echocardiography of \> 3.3 cm/m2 (for females) or 3.4 cm/m2 (for males) and/or LV ejection fraction ≤ 45%.
• Gene positive for a pathogenic mutation in the LMNA gene, as determined by a CLIA-certified clinical laboratory (mutations including but not limited to: splice-site, non-sense, deletion mutations, a mis-sense mutation in a highly conserved codon, a mis-sense mutation involving a major charge change, a mis-sense mutation previously associated with genetic dilated cardiomyopathy).
• Within 3 weeks prior to first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 350 m AND/OR ≥ 100 m and ≤ 450 m AND ≤ 60% predicted distance AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
• On the day before and day of first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 400 m (with the greater value within 10% of the lesser value) AND/OR ≥ 100 m and ≤ 475 m (with the greater value within 10% of the lesser value) AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
• Acceptable hematology, hepatic and renal function laboratory values within 3 weeks prior to first dose of study drug.
• Additional criteria exist.

You may not qualify if:

• Unstable clinical cardiac symptoms requiring unscheduled hospitalization within 60 days prior to study start.
• Clinically significant coronary artery disease, as per Investigator judgment.
• Currently receiving continuous intravenous (IV) inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation.
• Any of the following within 60 days prior to study start: Myocardial infarction, cardiac surgical procedures, acute coronary syndrome, hemodynamically destabilizing cardiac arrhythmia, serious systemic infection with evidence of septicemia, any major surgical procedure requiring general anesthesia.
• Uncorrected, hemodynamically significant primary valvular disease.
• Initiation of cardiac resynchronization therapy within 180 days prior to study start.
• Likelihood, in the Investigator's opinion, of undergoing cardiac transplantation, left ventricular assist device or other device implantation, or other cardiac surgery within the next 6 months; or of requiring continuous IV inotropic treatment, or referral for hospice or end-of-life treatment.
• Active malignancy (except surgically-curative basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma).
• Receiving chronic immunosuppressant therapy.
• Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C.
• Participation in any other investigational study of drugs or devices within 30 days prior to study start.
• Additional criteria exist.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

University of Colorado School of Medicine

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Meriter Wisconsin Heart

Madison, Wisconsin, 53713, United States

Location

Related Publications (4)

• 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

• MacRae CA, Taylor MRG, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study. Circ Genom Precis Med. 2023 Feb;16(1):e003730. doi: 10.1161/CIRCGEN.122.003730. Epub 2022 Dec 14.

  PMID: 36515663 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Laminopathies

Interventions

ARRY-371797

Condition Hierarchy (Ancestors)

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2014
• First Posted: February 7, 2014
• Study Start: February 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: October 14, 2020

Record last verified: 2020-10

Locations

US (6)