Clinical trial NCT05767346: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
Official title: A Phase 3, Multi-center, Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obstructive Hypertrophic Cardiomyopathy (oHCM)
Keywords: Obstructive Hypertrophic Cardiomyopathy
Aficamten
Metoprolol
oHCM
CK-3773274
CK-274
MAPLE-HCM
MAPLE
CY 6032
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2023-03-14
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy and safety of aficamten (CK-3773274) compared with metoprolol succinate in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction


Eligibility criteria: Inclusion Criteria:

* Participants who meet all the following criteria at screening may be included in the trial:

  * Males and females between 18 to 85 years of age, inclusive, at screening
  * Body mass index \< 35 kg/m2
  * Diagnosed with oHCM per the following criteria by cardiac magnetic resonance imaging (CMR) or echocardiography -

    * Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease and
    * Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory:

      1. ≥ 15 mm in one or more myocardial segments OR
      2. ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM
  * NYHA class II or III
  * Has a KCCQ-CSS score of ≤ 90 at screening
  * Has a screening echocardiogram with the following determined by the echocardiography core laboratory:

    * Resting LVOT-G \> 30 mm Hg and/or post-Valsalva LVOT-G ≥ 50 mmHg at screening AND
    * LVEF ≥ 60%
  * Hemoglobin ≥ 10g/dL
  * Respiratory exchange ratio (RER) ≥ 1.05 and peak oxygen uptake (pVO2) \< 100% predicted on the screening CPET per the core laboratory
  * Patients previously exposed to mavacamten are allowed to participate but must be off mavacamten for at least 8 weeks

Exclusion Criteria:

* Any of the following criteria will exclude potential participants from the trial:

  * Medical indication for either beta blocker or calcium-channel blockers prohibiting drug discontinuation other than oHCM
  * History of intolerance or medical contraindication to beta blocker therapy
  * Resting SBP of \> 160 mmHg
  * Resting heart rate of \> 100 bpm
  * Significant valvular heart disease

    1. Moderate-severe valvular aortic stenosis or fixed subaortic obstruction
    2. Mitral regurgitation not due to systolic anterior motion of the mitral valve (per Investigator judgment)
  * Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
  * History of LV systolic dysfunction (LVEF \< 45%) or stress cardiomyopathy at any time during their clinical course
  * Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
  * Documented room air oxygen saturation reading \< 90% at screening
  * Planned septal reduction treatment that cannot be deferred during the trial period
  * History of septal reduction therapy (surgical myectomy or alcohol septal ablation) within 6 months of screening
  * History of paroxysmal or persistent atrial fibrillation or atrial flutter. Atrial flutter treated with radio frequency ablation without recurrence within the last 6 months prior to screening is allowed.
  * Current or recent (\< 4 weeks) therapy with disopyramide
  * History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
  * Has received prior treatment with aficamten or previously intolerant (reduced LVEF requiring permanent drug discontinuation) to mavacamten

Primary outcomes:
measure: Change in peak oxygen uptake (pVO2) by cardiopulmonary exercise testing (CPET)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) Functional Class
timeFrame: Baseline to Week 24
measure: Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)
timeFrame: Baseline to Week 24
measure: Change in left ventricular mass index (LVMI)
timeFrame: Baseline to Week 24
measure: Change in left atrial volume index (LAVI)
timeFrame: Baseline to Week 24
measure: Change from baseline values in NT-proBNP
timeFrame: Baseline to Week 24
measure: Change in post-Valsalva LVOT-G
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Heart and Vascular Institute
state: Alaska
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Health - Sulpizio Cardiovascular Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center (Smidt Heart Institute)
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Fayetteville
country: United States
facility: Piedmont Fayette Hospital
state: Georgia
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center/New York Presbyterian Hospital
state: New York
city: Charlotte
country: United States
facility: Sanger Heart & Vascular Institute - HCM Clinic
state: North Carolina
city: Morrisville
country: United States
facility: Duke Health Center Arringdon
state: North Carolina
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Division of Heart Failure and Transplantation (Hospital of the University of Pennsylvania)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Ascension Saint Thomas Heart West
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: CHI St. Luke's Health Baylor-St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Falls Church
country: United States
facility: Inova Schar Heart and Vascular
state: Virginia
city: Campinas
country: Brazil
facility: Instituto de Pesquisa Clinica de Campinas - IPECC
state: SP
city: San Paolo
country: Brazil
facility: lnstituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
state: SP
city: Ibirapuera
country: Brazil
facility: Institutdo Danta Pazzanese
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumonlogie de Quebec - Universite Laval
city: Changsha
country: China
facility: Xiangya Second Hospital of Central South University
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
city: Marseille
country: France
facility: CHU La Timone
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Lariboisiere - APHP
city: Pessac
country: France
facility: Hopital Cardiologique Haut Leveque - CHU de Bordeaux
city: Rennes
country: France
facility: CHU Pontchaillou
city: Saint-Herblain
country: France
facility: Hopital Laennec - CHU de Nantes
city: Berlin
country: Germany
facility: Charite-Universitatsmedizin Berlin - Campus Virchow Klinikum
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Hebrew Medical Center- Ein Kerem
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Safed
country: Israel
facility: Ziv Medical Center
city: Florence
country: Italy
facility: AOU Careggi
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen Arrixaca
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Son Ferriol
country: Spain
facility: Hospital Universitario Son Llatzer
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Liverpool
country: United Kingdom
facility: Liverpool Heart and Chest Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospital NHS Trust - John Radcliffe Hospital - OCMR
Study officials:
affiliation: Cytokinetics
name: Scientific Leadership
role: STUDY_DIRECTOR
References: