This clinical trial is studying a new treatment for people who have Heart Failure with Preserved or Mildly Reduced Ejection Fraction and are also living with obesity. The study will test a medication called maridebart cafraglutide (also known as AMG 133), which is given as an injection under the skin. Some participants will receive the study medication while others will receive placebo. The purpose of this research is to determine if the medication can reduce heart failure-related hospital visits and deaths in people with this specific type of heart condition who also have a high body weight.
The treatment involves regular injections of either maridebart cafraglutide or placebo, given in addition to standard heart failure treatments that participants are already receiving. The study will monitor how the medication affects participants’ heart health, particularly focusing on heart failure events that require medical attention and heart-related deaths.
During the study, researchers will track various aspects of participants’ health, including their heart function and quality of life. They will use questionnaires to assess how participants are feeling and functioning in their daily activities. The study will also monitor other important heart-related events such as myocardial infarction (heart attack) and ischemic stroke.
1Initial evaluation
Your heart function will be evaluated to confirm that you have heart failure with preserved or mildly reduced ejection fraction (a condition where your heart pumps normally but doesn’t fill properly with blood).
Your body mass index (BMI) will be measured to confirm it is 30 or higher.
A blood test will check your NT-proBNP levels (a substance that indicates heart stress).
2Medical imaging
An echocardiogram (heart ultrasound) will be performed to examine your heart structure.
The test will measure various aspects of your heart, including chamber sizes and wall thickness.
3Treatment assignment
You will be randomly assigned to receive either maridebart cafraglutide (AMG 133) or a placebo.
The medication or placebo will be given as an injection under the skin (subcutaneous injection).
This is a double-blind study, which means neither you nor your doctor will know which treatment you are receiving.
4Treatment period
You will receive regular injections of either the study medication or placebo.
The treatment period will continue until the study ends in September 2030.
Your heart health will be monitored throughout the study period.
You will complete questionnaires about your symptoms and quality of life at various points during the study, including at week 48.
5Monitoring
Regular check-ups will track your heart health and any heart-related events.
The study will monitor for events such as hospitalization for heart failure, urgent heart failure visits, or heart-related health issues.
Your overall health and any changes in your condition will be regularly assessed.
Who Can Join the Study?
Must be at least 18 years old or older if required by local law
Must have a Body Mass Index (BMI) of 30 or higher at screening (BMI is a measure of body fat based on height and weight)
Must have been diagnosed with heart failure for at least 30 days before screening with New York Heart Association (NYHA) Class II-IV symptoms at screening (symptoms ranging from mild to severe limitations in physical activity)
Must be on stable heart failure medications for at least 14 days before screening
Must have a left ventricular ejection fraction greater than 40% measured within the last 12 months (this measures how well your heart pumps blood)
Must have elevated NT-proBNP levels (a blood test that helps diagnose heart failure):
– Above 300 pg/mL for patients with normal heart rhythm
– Above 600 pg/mL for patients with atrial fibrillation or flutter
Must have at least one of these conditions:
– Specific heart structure changes shown on an echocardiogram
– Hospital stay for heart failure requiring IV medication in the past 12 months
– Evidence of high heart filling pressures in the past 12 months
For participants with Type 2 diabetes: Must be on stable diabetes treatment (diet, exercise, or medications) for at least 30 days before starting the study
Who Cannot Join the Study?
Age below 18 years old
Current pregnancy or breastfeeding
Body Mass Index (BMI) less than 30 kg/m² (a measurement that uses height and weight to determine if someone is overweight)
Ejection fraction (the percentage of blood pumped out of the heart with each beat) outside the preserved or mildly reduced range
Severe heart failure symptoms that require immediate hospitalization
History of severe allergic reactions to similar medications
Participation in other clinical trials within the past 30 days
Unstable heart condition requiring urgent medical intervention
Severe kidney or liver disease
Inability to provide informed consent
History of drug or alcohol abuse within the past year
Life-threatening illness other than heart failure
Use of medications that could interact with the study drug
Mental conditions that could interfere with study participation
Maridebart cafraglutide is a new investigational medication being studied for treating heart failure in people who also have obesity. It is designed to help patients who have a specific type of heart failure where their heart can still pump blood relatively well (preserved or mildly reduced ejection fraction). The medication is being tested as an additional treatment alongside standard heart failure medications to see if it can reduce hospitalizations due to heart failure and improve survival rates.
Placebo is an inactive substance that looks identical to the study medication but contains no active ingredients. It is used to compare the effects of the active medication and determine if maridebart cafraglutide provides real benefits to patients.
Heart Failure with Preserved Ejection Fraction – A type of heart failure where the heart muscle contracts normally but doesn’t relax properly between beats, reducing the heart’s ability to fill with blood. This condition leads to less blood being pumped throughout the body, causing symptoms like shortness of breath and fatigue. The heart maintains a normal ejection fraction of 50% or higher, despite the heart’s compromised filling ability.
Heart Failure with Mildly Reduced Ejection Fraction – A form of heart failure where the heart’s pumping function is slightly decreased, with ejection fraction typically ranging between 40% and 49%. The heart muscle becomes mildly weakened but can still pump a significant portion of blood with each contraction. This condition can cause similar symptoms to other types of heart failure, including reduced exercise tolerance and fluid retention.
Obesity – A chronic condition characterized by excessive accumulation of body fat, typically measured by a Body Mass Index (BMI) of 30 or higher. The condition develops gradually as a result of consuming more calories than the body uses over an extended period. It affects multiple body systems and can impact overall physical functioning. The excess weight puts additional strain on the body’s organs and skeletal system.
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