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

NCT02351856 | Completed Phase 2 Results

• 2 other identifiers: ARRAY-797-001C4411001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief Summary

This is a rollover study designed to investigate the safety and effectiveness of investigational study drug ARRY-371797 in patients who previously received ARRY-371797 in a study for patients with LMNA-related dilated cardiomyopathy sponsored by Array BioPharma and may, in the Investigator's opinion, derive benefit from continued treatment.

Conditions

LMNA-Related Dilated Cardiomyopathy

Keywords

laminopathy; ARRY-797

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)

• Number of Participants With Change From Baseline Value in Clinical Laboratory Hematology Test Results to Worst Value

  In this outcome measure, number of participants with baseline laboratory hematology values as per National Cancer Institute Common Terminology Criteria (NCI-CTC) grade (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) and corresponding changes/shift to the worst CTC grades post baseline were presented. Shift data have been reported for hematology parameters: hemoglobin (g/L), platelets (10\^9/L), leukocytes (10\^9/L), neutrophils (10\^9/L), lymphocytes (10\^9/L) and eosinophils (10\^9/L). Baseline was defined as last non-missing value before the initial administration of study treatment in parent study and worst post-baseline value defined as worst value between first dose of study drug up to the maximum of 282 weeks. Only those categories in which at least 1 participant had data were reported.

  Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)

• Number of Participants With Change From Baseline Value in Clinical Laboratory Chemistry Test Results to Worst Value

  In this outcome measure, number of participants with baseline laboratory chemistry values as per NCI-CTC grade (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) and corresponding changes/shift to the worst CTC grades post baseline were presented. Shift data have been reported for laboratory parameters: alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, international unit per liter (IU/L), albumin, bilirubin, urea nitrogen, calcium, creatinine, glucose, magnesium, protein and phosphate grams per deciliter (g/dL), potassium and sodium, millimol per liter (mmol/L). Baseline was defined as last non-missing value before the initial administration of study treatment in parent study and worst post-baseline value defined as worst value between first dose of study drug up to the maximum of 282 weeks. Only those categories in which at least 1 participant had data were reported.

  Baseline, Post-Baseline (anytime from first dose of study drug to maximum duration of up to 282 weeks)

• Number of Participants With Abnormal Physical Examination Findings

  Physical examination included the assessment of skin, head, ears, eyes, nose, throat, cardiovascular system, abdomen and lungs. Abnormality in physical examination were based on investigator's discretion.

  Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)

• Number of Participants With Abnormalities in Vital Signs

  Following vital signs parameters were analyzed using prespecified range of results for signs of clinical significance: systolic blood pressure in millimeters of mercury (mmHg): \<90 mmHg and ≥160 mmHg, diastolic blood pressure: \<60 mmHg and ≥100 mmHg, heart rate in beats per minute (bpm): \<40bpm and \>120 bpm, temperature in degree Celsius (C): \<36.1 and \> 37.2 degree C.

  Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)

• Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

  Following ECG parameters were analyzed using prespecified range of results for signs of clinical significance: heart rate: \<40bpm and \>120 bpm; QT/QTcF (QT interval corrected using Fridericia's formula) criteria: QT interval \>500 ms; QTcF interval \>450 ms; or change from baseline in QTcF \>30 ms.

  Baseline up to 30 days after last dose of study drug (i.e., maximum up to 282 weeks)

Secondary Outcomes (10)

• Change From Baseline in Six Minute Walk Test (6MWT) Distance at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit

  Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)

• Change From Baseline in Left Ventricular End Systolic Index (LVESVI) and Left Ventricular End Diastolic Volume Index (LVEDVI) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit

  Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)

• Change From Baseline in Left Ventricular Mass (LVM) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit

  Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit

  Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)

• Change From Baseline in Left Ventricular Mass (LVM) to Volume Ratio at Day 1, Weeks 24, 48, 72, 96 and Early Termination Visit

  Baseline, Day 1, Weeks 24, 48, 72, 96 and early termination visit (anytime within the maximum duration of up to 282 weeks)

Study Arms (1)

ARRY-371797

EXPERIMENTAL

Drug: ARRY-371797, p38 inhibitor, oral

Interventions

ARRY-371797, p38 inhibitor, oral DRUG

multiple dose, single schedule

ARRY-371797

Eligibility Criteria

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

You may qualify if:

• Received ARRY-371797 as treatment for a genetic dilated cardiomyopathy secondary to LMNA mutations in a clinical study sponsored by Array BioPharma.
• May, in the opinion of the Investigator, benefit from continued ARRY-371797 treatment.
• Additional criteria exist.

You may not qualify if:

• Discontinued treatment in the parent study for any reason other than study completion or Sponsor termination of the study.
• Additional criteria exist.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Meriter Wisconsin Heart

Madison, Wisconsin, 53713, United States

Location

Related Publications (3)

• 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

• 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

• Judge DP, Lakdawala NK, Taylor MRG, Mestroni L, Li H, Oliver C, Angeli FS, Lee PA, MacRae CA. Long-Term Efficacy and Safety of ARRY-371797 (PF-07265803) in Patients With Lamin A/C-Related Dilated Cardiomyopathy. Am J Cardiol. 2022 Nov 15;183:93-98. doi: 10.1016/j.amjcard.2022.08.001. Epub 2022 Sep 13.

  PMID: 36114020 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

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 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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: January 30, 2015
• Study Start: February 2, 2015
• Primary Completion: December 21, 2020
• Study Completion: December 21, 2020
• Last Updated: March 31, 2022
• Results First Posted: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (4)