Clinical trial NCT07023341: A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Official title: A Phase 3, Open Label, Single Arm Study to Evaluate Efficacy, Safety and Tolerability of Aficamten in Adult Japanese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Obstructive Hypertrophic Cardiomyopathy
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2025-06-17
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Researchers are looking for a better way to treat Japanese people who have symptomatic obstructive hypertrophic cardiomyopathy (symptomatic oHCM).

Obstructive hypertrophic cardiomyopathy (oHCM) is a type of heart disease where the heart muscles become thicker than normal due to over contraction. This thickening makes it harder than normal due to over contraction. This thickening makes it harder for the heart to pump blood out to the rest of the body. In symptomatic oHCM people with the condition experience symptoms like shortness of breath, chest pain, fainting, high blood pressure and irregular heartbeats.

The study treatment aficamten, also called BAY3723113, is under development to treat symptomatic oHCM. It aims to reduce the activity of cardiac myosin, a protein that helps heart muscles to contract, and thereby preventing over contraction and muscle thickening.

Although treatment options are available for symptomatic oHCM, there is still need for other treatment options that help target the root cause of the condition. In this study, researchers want to understand about the effects and long-term safety of aficamten in Japanese people with symptomatic oHCM.

The main purpose of the study is to learn how well aficamten works in Japanese with symptomatic oCHM.

For this, the researchers will check how participant's heart blood flow changes after 6 months of treatment. They do this by measuring the pressure needed for blood to leave the heart using a test called the left ventricular outflow tract (LVOT) gradient and a special breathing technique called Valsava maneuver.

Researchers will also look for:

* the number of participants who will have at least 1 level improvement on a scale doctors use to assess the effect of heart problems on daily activities after 3 and 6 months of treatment
* the change in the impact of heart problems on participant's daily lives based on their feedback on a questionnaire called Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) after 3 and 6 months of treatment.

This study will have 2 treatment periods: main treatment period and long-term treatment period. During the main treatment period, participants will take aficamten tablets once daily by mouth for up to 6 months. After completing this period, the participants who can join the long-term treatment period will continue taking aficamten until the drug becomes commercially available in Japan or the study ends.

Each participant will be in the study as long as they benefit from the treatment.

Participants will visit the study site:

* once before the treatment starts
* 9 times with a gap of 2 to 4 weeks between the visits during treatment under the main treatment period, and in the long-term treatment period, participants will visit almost every 3 months until the treatment ends.
* then 2 more times with a gap of 1 month between the visits after the treatment ends.

During the study, the study doctors and their team will:

* check participant's health by performing tests such as blood and urine tests, and checking heart health using an electrocardiogram (ECG) and echocardiogram (ECHO)
* ask the participants questions about how they are feeling and what adverse events are they having

An adverse event is any medical problem that a participant has during a study. Study doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatment. In addition, the participants will be asked to complete a questionnaire on quality of life at certain time points during the study.

If the participant benefits from the treatment, treatment with aficamten after the end of the study might be possible.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 to 85 years of age inclusive, at the time of signing the informed consent.
* Diagnosed with HCM per the following criteria:

  1. Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac disease and
  2. Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory of:

     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
* Has resting LVOT-G ≥ 30 mmHg and Valsalva LVOT-G =50 mmHg during screening as determined by the echocardiography core laboratory
* LVEF ≥ 60% at screening as determined by the echocardiography core laboratory
* NYHA Functional Class II or III at screening
* Hemoglobin ≥10 g/dL at screening
* Body mass index \<35 kg/m²
* Japanese
* Patients on beta-blockers, verapamil, diltiazem, or disopyramide/cibenzoline should have been on a stable regimen for \>6 weeks prior to the first dose of aficamten and anticipate remaining on the same medication regimen at least during the main study treatment period. Patients treated with disopyramide or cibenzoline must also be concomitantly treated with a beta blocker and/or calcium channel blocker.

Exclusion Criteria:

* Significant valvular heart disease (per investigator judgement)

  1. Moderate-severe valvular aortic stenosis and/or regurgitation
  2. Moderate-severe mitral regurgitation not due to systolic anterior motion of the mitral valve
* Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics oHCM (e.g., Noonan syndrome, Fabry disease, amyloidosis)
* History of LV systolic dysfunction (LVEF \<45%) or stress cardiomyopathy at any time during their clinical course
* Documented paroxysmal atrial fibrillation during the screening period
* Paroxysmal or persistent/permanent atrial fibrillation is only excluded IF:
* Rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 6 months prior to screening
* Rate control and anticoagulation have not been achieved for at least 6 months prior to screening
* Has been treated with SRT (surgical myectomy or percutaneous alcohol septal ablation) or cannot postpone plans for SRT until after the study period
* History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening
* Has received prior treatment with aficamten or mavacamten

Primary outcomes:
measure: Change in Valsava LVOT-G
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Change in resting LVOT-G
timeFrame: From baseline to Weeks 12 and 24
measure: Change in Valsava LVOT-G
timeFrame: From baseline to Week 12
measure: Change in N-terminal prohormone brain natriuretic peptide (NT-proBNP) value
timeFrame: From baseline to Week 24
measure: Proportion of patricipants with ≥1 class improvement in New York Heart Association (NYHA) Functional Class
timeFrame: From baseline to Weeks 12 and 24
measure: Change in KCCQ-CSS score
timeFrame: From baseline to weeks 12 and 24
measure: Incidence of left ventricular ejection fraction (LVEF) <40%
timeFrame: From baseline to last follow up, up to 4 weeks
measure: Incidence of LVEF <50%
timeFrame: From baseline to last follow up, up to 4 weeks
measure: Incidence of treatment emergent adverse events (TEAE)
timeFrame: From baseline to last follow up, up to 4 weeks
measure: Incidence of treatment emergent serious adverse events (TESAE)
timeFrame: From baseline to last follow up, up to 4 weeks
Other outcomes:
Locations:
city: Himeji
country: Japan
facility: Hyogo Prefectural HarimaHimeji General Medical Center
state: Hyogo
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Morioka-shi
country: Japan
facility: Iwate Prefectural Central Hospital
state: Iwate
city: Sagamihara
country: Japan
facility: Kitasato University Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: SHOWA Medical University Fujigaoka Hospital
state: Kanagawa
city: Nankoku
country: Japan
facility: Kochi Medical School Hospital
state: Kochi
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
state: Mumamoto
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Ginowan City
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa
city: Moriguchi
country: Japan
facility: Matsushita Memorial Hospital
state: Osaka
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Suita
country: Japan
facility: The University of Osaka Hospital
state: Osaka
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Bunkyo
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Fuchu
country: Japan
facility: Sakakibara Heart Institute
state: Tokyo
city: Koto
country: Japan
facility: Showa Medical University Koto Toyosu Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Saiseikai Fukuoka General Hospital
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
Study officials:
References: