A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM

A Phase III, Randomized, Double-blinded, Placebo-controlled Clinical Study With A Long-term Extension to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Mavacamtenis a novel, small molecule, selective allosteric inhibitor of cardiac-specific myosin, for the treatment of patients with symptomatic oHCM. This study will assess the efficacy and safety of mavacamten in Chinese adults with symptomatic oHCM.

Study Overview

• Status: Active, not recruiting
• Conditions: Obstructive Hypertrophic Cardiomyopathy
• Intervention / Treatment: Drug: Mavacamten; Drug: Placebo

Detailed Description

This is a randomized, double-blinded, placebo-controlled clinical study witha long-term extension to evaluate the efficacy and safety of mavacamten in Chinese adults with symptomatic oHCM. Approximately 81eligible participants will be enrolled and randomized in a 2:1 ratio (mavacamten:placebo). Participants will receive mavacamten or matching placebofor 30 weeks indouble-blinded manner. After 30-week double-blinded placebo-controlled treatment, eligible participants will receive mavacamten for additional 48 weeks (placebogroup: switch from placebo to mavacamten, mavacamten group: maintain on mavacamten).

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is at least 18 years old at screening.
• Body weight is greater than 45 kg at screening.
• Has adequate acoustic windows to enable accurate TTEs
• Diagnosed with oHCM
• Has documented LVEF ≥ 55% at rest.
• Has a valid measurement of Valsalva LVOT peak gradient at screening
• Has NYHA Class II or III symptoms at screening
• Female participants must not be pregnant or lactating
• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent according to national, local, and institutional guidelines before the first study specific procedure.

Exclusion Criteria:

• Participated in a clinical trial in which the participant received any investigational drug (or is currently using an investigational device) within 30 days prior to screening, or at least 5 times the respective elimination half-life (if known), whichever is longer.
• Causing cardiac hypertrophy in other reasons
• Previously participated in a clinical study with mavacamten.
• Hypersensitivity to any of the components of the mavacamten formulation.
• Current treatment (within 14 days prior to screening) or planned treatment during the double-blinded treatment with a combination of beta-blockers and verapamil or a combination of beta-blockers and diltiazem.
• Has been successfully treated with invasive septal reduction
• Has documented obstructive coronary artery disease
• Has known moderate or severe (as per investigator's judgment) aortic valve stenosis, constrictive pericarditis, or clinically significant congenital heart disease at screening.
• Has any acute or serious comorbid condition that, in the judgment of the investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.
• History of malignant disease within 10 years of screening
• Has safety laboratory parameters outside normal limits at screening as assessed by the local laboratory
• Has a positive serologic test at screening for infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus surface antigen.
• Known uncured COVID-19 (coronavirus disease 2019) infection or with severe complication before screening.
• Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• Prior treatment with cardio toxic agents.
• Unable to comply with the study requirements, including the number of required visits to the clinical site.
• Is a first degree relative of personnel directly affiliated with the study at the clinical study site, any study vendor, or the study sponsor.
• Identified as alcohol addicts.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mavacamten; Mavacamten Capsules	Drug: Mavacamten; Mavacamten Capsules; Other Names: MYK-461; BMS-986327
Placebo Comparator: placebo; Matching Placebo Capsules	Drug: Placebo; Matching PBO capsules during placebo controlled period，and mavacamten capsules during long term extension period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 30 in Valsalva left ventricular outflow tract (LVOT) peak gradient	To compare the effect of a 30-week course of mavacamten with placebo on Valsalva LVOT peak gradient as determined by Doppler echocardiography	30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to Week 30 in resting LVOT peak gradient	To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.	30 weeks
Proportion of participants achieving a Valsalva LVOT peak gradient < 30 mmHg at Week 30	To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.	30 weeks
Proportion of participants achieving a Valsalva LVOT peak gradient < 50 mmHg at Week 30.	To compare the effect of a 30-week course of mavacamten with placebo on LVOT obstruction.	30 weeks
Proportion of participants with at least 1 class improvement in New York Heart Association (NYHA) functional classification from baseline to Week 30	To compare the effect of a 30-week course of mavacamten with placebo on clinical symptoms	30 weeks
Change from baseline to Week 30 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)	To compare the effect of a 30-week course of mavacamten with placebo on Participant-Reported health status individually	30 weeks
Change from baseline to Week 30 in N-terminal pro-B-type natriuretic peptide (NT-proBNP)	To compare the effect of a 30-week course of mavacamten on cardiac biomarkers	30 weeks
Change from baseline to Week 30 in cardiac troponin	To compare the effect of a 30-week course of mavacamten on cardiac biomarkers	30 weeks
Change from baseline to Week 30 in left ventricular (LV) mass index	To compare the effect of a 30-week course of mavacamten with placebo on LV mass evaluated by cardiac magnetic resonance (CMR) imaging.	30 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving NYHA Class I and resting and Valsalva LVOT peak gradient < 30 mmHg at Week 30 Change from baseline to Week 30 in echocardiographic indices of cardiac structure and systolic and diastolic function	To assess the effect of a 30-week course of mavacamten on cardiac function and structure as evaluated by echocardiography To assess the effect of a 30-week course of mavacamten on cardiac function and structure as evaluated by CMR imaging To assess the effect of a 30-week course of mavacamten on Participant-Reported health status	30 weeks
Change from baseline to Week 30 in myocardial fibrosis Change from baseline to Week 30 in cellular hypertrophy, cardiac structure, and function Change from baseline to Week 30 in Total Symptom Score and Overall Summary Score from KCCQ	To assess the effect of a 30-week course of mavacamten on cardiac function and structure as evaluated by echocardiography To assess the effect of a 30-week course of mavacamten on cardiac function and structure as evaluated by CMR imaging To assess the effect of a 30-week course of mavacamten on Participant-Reported health status	30 weeks
Incidence of LVEF < 50% determined by TTE Incidence and severity of TEAEs, and treatment-emergent SAEs	To assess the safety of mavacamten during the 30-week double-blinded, placebo-controlled treatment period	30 weeks
Incidence of major adverse cardiac events (MACEs; CV death, non-fatal stroke, non-fatal myocardial infarction) Incidence of hospitalizations (due to CV and non-CV events)	To assess the safety of mavacamten during the 30-week double-blinded, placebo-controlled treatment period	30 weeks
Incidence of HF events, including hospitalizations and urgent emergency room/outpatient visits for HF Incidence of atrial fibrillation/flutter (new from screening, and recurrent) Incidence of ICD therapy and resuscitated cardiac arrest	To assess the safety of mavacamten during the 30-week double-blinded, placebo-controlled treatment period	30 weeks
Incidence of ventricular tachyarrhythmias including ventricular tachycardia, ventricular fibrillation, and Torsades de Pointe Incidence of adverse events of special interest (AESIs; symptomatic overdose, outcomes of pregnancy, LVEF ≤ 30%)	To assess the safety of mavacamten during the 30-week double-blinded, placebo-controlled treatment period	30 weeks

Collaborators and Investigators

• Sponsor: LianBio LLC
• Investigators: Principal Investigator: Shuyang Zhang, M.D., Ph.D., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2022
• Primary Completion (Actual): March 6, 2023
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Mavacamten
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: LB2001-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No