Phase 3 Study of ARRY-371797 in Lamin A/C Gene Mutation-related DCM

  • Research type

    Research Study

  • Full 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



  • Contact name

    Perry Elliott

  • Contact email

  • Sponsor organisation

    Array BioPharma Inc.

  • Eudract number


  • Identifier


  • Duration of Study in the UK

    1 years, 8 months, 15 days

  • Research summary

    Research Summary:

    This is a phase 3, Multinational, Randomised, Placebo-controlled Study of ARRY-371797 (study drug) in Patients with Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation. The main purpose of the research study is to evaluate the
    effect of the study drug ARRY-371797 on the patients’ ability to walk over a 6-minute period (as measured by the 6-minute walk test) compared to placebo in at least 120 patients with symptomatic New York Heart Association (NYHA)Class II/III/IV dilated cardiomyopathy (DCM) secondary to LMNA mutations. NYHA functional Class IV patients (up to approximately 40) will also be enrolled at a 1:1 randomisation and will be assessed for overall safety and time from randomisation to heart failure related hospitalisation or death.
    The study will be conducted in 2 parts: a randomised, double-blind treatment period for at least 24 weeks, followed by an ARRY-371797 open-label treatment period where patients will be eligible to receive 400 mg ARRY-371797 (study drug) taken twice a day. Study procedures include medical history, physical examination, vital signs, blood and urine sample collection, ECG, Arrhythmia assessment, and 6 minute walk test, Echocardiogram.
    Array BioPharma Inc. is sponsoring this trial and it is expected that approximately 160 patients with genetic dilated cardiomyopathy, who are 18 years and older, will participate in this study in the UK Argentina, Belgium, Canada, France, Germany, Italy, Mexico, Netherlands, Norway, Spain and the USA with an expected 12 patients from the UK.

    Summary of Results:

    • Based on the interim analysis, this study was terminated due to futility. Final analysis confirmed the findings of the interim analysis.
    • There was no difference observed on the primary endpoint of change from baseline in 6MWT at Week 24 for NYHA Class II/III participants (2 sided p-value=0.818). The median (95% CI) difference between treatment groups in change from baseline in 6MWT at Week 24 was 4.936 ( 24.246, 34.118) meters.
    • The results of the key secondary analyses of changes from baseline in KCCQ-PL and KCCQ-TSS, as well as change from baseline in NT proBNP at Week 24 were consistent with the primary results.
    • There were no new safety signals detected.
    • No clinically meaningful differences in TEAEs, clinical laboratory tests, vital signs, ECGs, or other safety-related observations were found between the PF 07265803 and placebo groups.
    • Sixty-nine (89.6%) participants (35 for PF-07265803, 34 for placebo) had at least 1 TEAE during the study, and a numerically higher proportion of participants in the PF-07265803 group (65.0%) had at least 1 TEAE which was considered related to the study intervention compared to the placebo group (24.3%).
    • A numerically higher proportion of participants in the placebo group (56.8%) experienced SAEs compared to the PF-07265803 group (25.0%); 4 participants (all in the PF-07265803 group) had treatment-related SAEs.
    • Fifteen (19.5%) participants (9 [22.5%] for PF-07265803, 6 [16.2%] for placebo) discontinued from the study intervention due to AE, of whom 8 participants (6 for PF 07265803, 2 for placebo) discontinued due to treatment related AEs.
    • Twenty-one (27.3%) participants (16 [40.0%] for PF-07265803, 5 [13.5%] for placebo) had dose changed or interrupted due to AEs, of whom 15 participants (13 for PF 07265803, 2 for placebo) had dose changed or interrupted due to treatment-related AEs.
    • There were 6 deaths reported in the study. In the PF-07265803 group, 3 deaths were caused by pancreatic neoplasia, ventricular tachycardia, and anoxic brain injury from sequelae of primary graft dysfunction post heart transplant and worsening ventricular tachycardia; in the placebo group, 3 deaths were caused by bacterial pneumonia, respiratory failure, and disease progression. Two participants (1 in each group) died during the on-treatment period. No deaths were assessed as related to study interventions.
    • No participants had an event meeting the criteria for possible Hy’s Law.
    • There were numerically fewer WHF events reported in the PF-07265803 group compared with placebo. Due to the low number of evaluable participants and events, the results should be interpreted with caution.
    • The OS was similar between the PF-07265803 and placebo groups.

  • REC name

    London - Westminster Research Ethics Committee

  • REC reference


  • Date of REC Opinion

    14 Dec 2018

  • REC opinion

    Further Information Favourable Opinion