Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity

Phase
Recruitment status
Participants
Lead sponsor
Start date
Number of sites

Summary
This trial will examine if maridebart cafraglutide as an adjunct to standard of care will lead to a reduction in heart failure (HF) events such as HF hospitalizations and urgent HF visits, cardiovascular (CV) deaths and improvement in HF symptoms in participants with HF with preserved ejection fraction (HFpEF) and HF with mildly reduced ejection fraction (HFmrEF) who are obese. This is a phase 3, global, multicenter, 2-part trial with a double-blind period and an open-label extension (OLE). The trial is event-driven, and Part 1 will conclude when approximately 850 primary endpoint events have occurred.
Acronym
Short title
Maridebart Cafraglutide in Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity
Official title
A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Maridebart Cafraglutide on Mortality and Morbidity in Participants Living With Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Obesity (MARITIME-HF)

Control arm
Registry reports results
Listing at source
Recruitment status
Phase
Study type
Interventional

Completion date
First posted
Registry last updated
Primary completion date
Start date

Participants
Participant count basis
Planned participants
Protocol amendments
Number of sites

Data monitoring committee
Registry sponsor category
Lead sponsor
Source registry
ClinicalTrials.gov

Registry ID
ClinicalTrials.gov ID
Registry record
Open registry record

Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design

  1. Time to First Occurrence of a Composite Endpoint Consisting of: CV Death or HF Events

    Timeframe: Up to approximately 35 months

    Heart Failure events include: hospitalization for HF or urgent HF visits.

  1. Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

  2. Change from Baseline in the KCCQ Total Symptom Score (TSS) for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-TSS assesses symptom frequency and burden, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

  3. Total Number of HF Events Including First and Recurrent HF Events

    Timeframe: Up to approximately 35 months

  4. Time to First Occurrence of a Composite Endpoint Consisting of: Myocardial Infarction (MI), Ischemic Stroke, CV Death (Major Adverse Cardiac Events [MACE]), or HF Events

    Timeframe: Up to approximately 35 months

  5. Time to First Event of a Composite Nephropathy Endpoint

    Timeframe: Up to approximately 35 months

    The composite nephropathy endpoint consists of: persistent macroalbuminuria, persistent ≥ 40% reduction in estimated glomerular filtration rate (eGFR), onset of persistent eGFR \< 15 mL/min/1.73 m\^2, initiation of chronic renal replacement therapy (dialysis or transplantation), CV or renal death.

  6. Change in eGFR Slope (Total)

    Timeframe: Baseline up to approximately 35 months

  7. Change in eGFR Slope (Chronic)

    Timeframe: From 4 months up to approximately 35 months

  8. Time to Onset of Type 2 Diabetes Mellitus (T2DM) in Participants with Prediabetes

    Timeframe: Up to approximately 35 months

  9. Time to the First HF Event

    Timeframe: Up to approximately 35 months

  10. Change from Baseline in the Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Timeframe: Baseline and Week 72

  11. Change from Baseline in Body Mass Index (BMI) (kg/m^2)

    Timeframe: Baseline and Week 72

  12. Change from Baseline in the Waist Circumference (cm)

    Timeframe: Baseline and Week 72

  13. Change from Baseline in the Urine Albumin-to-creatinine Ratio (uACR)

    Timeframe: Baseline and Week 72

  14. Change from Baseline in the Hemoglobin A1c (HbA1c [%, mmol/mol]) and fasting plasma glucose (mg/dL)

    Timeframe: Baseline and Week 72

  15. Percent Change from Baseline in the High-sensitivity C Reactive Protein (hs-CRP)

    Timeframe: Baseline and Week 72

  16. Percent Change from Baseline in the Body Weight (kg)

    Timeframe: Baseline and Week 72

  17. Percent Change from Baseline in Total Cholesterol

    Timeframe: Baseline and Week 72

  18. Percent Change from Baseline in Non-high-density Lipoprotein Cholesterol (non-HDL-C)

    Timeframe: Baseline and Week 72

  19. Percent Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C), HDL-C, Triglycerides (TG), Very Low-density Lipoprotein Cholesterol (VLDL-C)

    Timeframe: Baseline and Week 72

  20. Total All-cause Hospitalizations (First and Recurrent Time to Event)

    Timeframe: Up to approximately 35 months

  21. Number of Participants Achieving ≥ 5-point Change in KCCQ-CSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

  22. Number of Participants Achieving ≥ 10-point Change in KCCQ-CSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

  23. Number of Participants Achieving an Anchor-based Change in KCCQ-CSS Score From Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life. The Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) can be used as anchors to estimate within-patient change in the KCCQ-CSS score.

  24. Number of Participants Achieving ≥ 5-point Change in KCCQ-TSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-TSS assesses symptom frequency and burden, ranging from 0 to 100, with higher scores indicating better functioning and quality of life. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

  25. Number of Participants Achieving ≥ 10-point Change in KCCQ-TSS Score from Baseline for Participants with Baseline KCCQ-CSS Score ≤ 80

    Timeframe: Baseline and Week 48

    The KCCQ is a 23-item disease-specific measure for participants with HF, measuring the participant's perception of their health status. The KCCQ-TSS assesses symptom frequency and burden, ranging from 0 to 100, with higher scores indicating better functioning and quality of life. The KCCQ-CSS assesses symptoms and physical limitations, ranging from 0 to 100, with higher scores indicating better functioning and quality of life.

And 8 more, listed on the interactive page.

Sources for outcomes

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
99 Years
Healthy volunteers
No

  • Age ≥ 18 years at the time of informed consent.
  • BMI ≥ 30.0 kg/m^2 at randomization.
  • HF diagnosed for at least 30 days with New York Heart Association (NYHA) Class II-IV at the time of informed consent.
  • Managed with HF standard of care therapies.
  • Left ventricular ejection fraction (LVEF) of > 40% within 12 months before randomization.

  • History of any of the following within 60 days prior to or during screening: Type I (spontaneous) MI, valvular replacement or repair, coronary revascularization, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke.

  • HF due to: hypertrophic cardiomyopathy, infiltrative cardiomyopathy, active or chronic myocarditis, constrictive pericarditis, cardiac tamponade, arrhythmogenic right ventricular or left ventricular cardiomyopathy/dysplasia, uncorrected primary valvular heart disease, clinically significant congenital heart disease.

  • Hospitalized with acute decompensated HF at the time of or during the screening period.

  • Type 1 diabetes mellitus, or any type of diabetes with the exception of T2DM or history of gestational diabetes.

  • For participants with a prior diagnosis of T2DM (including those diagnosed during screening):

    1. HbA1c > 10.0% (86 mmol/mol) at screening
    2. Uncontrolled diabetes requiring immediate therapy
    3. History of diabetic ketoacidosis or hyperosmolar state/coma within 12 months before randomization
    4. One or more episodes of severe hypoglycemia within 6 months before randomization and/or history of hypoglycemia unawareness
    5. History or presence of either proliferative diabetic retinopathy, or diabetic maculopathy, or severe non-proliferative diabetic retinopathy; or currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema.
  • SBP ≥ 180 mmHg during the screening period, or on three or more blood pressure-lowering drugs with a SBP > 160 mmHg during the screening period (including day 1 prior to randomization).

  • History of chronic pancreatitis or acute pancreatitis in the 180 days before screening or during the screening period.

  • Any personal lifetime history of, or family history(first-degree relative[s]) of medullary thyroid carcinoma or MEN-2.

  • eGFR < 20 mL/min/1.73 m^2 (CKD-EPI creatinine (Cr)-cystatin C equation) or receiving dialysis at screening.

  • Calcitonin ≥ 50 ng/L (pg/mL) at screening.

  • Acute or chronic hepatitis.

  • Any of the following psychiatric history:

    1. History of unstable major depressive disorder or other severe psychiatric disorder within 2 years prior to screening or during the screening period
    2. Lifetime history of suicide attempt
    3. History of non-suicidal self-injury within 5 years prior to screening or during the screening period.
  • History of any other condition that, in the opinion of the investigator, may preclude the participant from following the protocol and completing the trial.

  • Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA), glucose-dependent insulinotropic polypeptide (GIP) agonists or antagonists, or amylin analogs within 90 days prior to or during the screening period or planned use during the conduct of the trial.

Sources for eligibility

  • University of Alabama Saint Vincent's BirminghamBirmingham, United StatesRecruiting
  • SEC Clinical ResearchDothan, United StatesRecruiting
  • Eastern Shore Research InstituteFairhope, United StatesRecruiting
  • Heart Center Research LLCHuntsville, United StatesRecruiting
  • HonorHealthPhoenix, United StatesRecruiting
  • Medical Advancement Centers of ArizonaPhoenix, United StatesRecruiting
  • Pima Heart and Vascular Clinical ResearchTucson, United StatesRecruiting
  • Yuma Clinical TrialsYuma, United StatesRecruiting
  • Arkansas CardiologyLittle Rock, United StatesRecruiting
  • National Heart InstituteBeverly Hills, United StatesRecruiting
  • Valley Clinical Trials, LLC dba Flourish ResearchCovina, United StatesRecruiting
  • National Institute of Clinical ResearchHuntington Beach, United StatesRecruiting
  • 310 Clinical ResearchInglewood, United StatesRecruiting
  • Radin Cardiovascular Medical GroupNewport Beach, United StatesRecruiting
  • Valley Clinical TrialsNorthridge, United StatesRecruiting
  • University of California IrvineOrange, United StatesRecruiting
  • Empire Clinical ResearchPomona, United StatesRecruiting
  • San Diego Cardiac CenterSan Diego, United StatesRecruiting
  • NorthBay Clinical Research LLCSanta Rosa, United StatesRecruiting
  • Manshadi Heart InstituteStockton, United StatesRecruiting
  • Cardiology Associates of Fairfield County PCStamford, United StatesRecruiting
  • Orlando Heart and Vascular InstituteAltamonte Springs, United StatesRecruiting
  • D and H Tamarac Research CenterAventura, United StatesRecruiting
  • Excel Medical Clinical TrialsBoca Raton, United StatesRecruiting
  • Cardiovascular and Vein Center of FloridaBradenton, United StatesRecruiting

And 603 more, listed on the interactive page.

Sources for sites

Sources for references

Related records

Drugs (1)

Lead sponsors (1)

Conditions (2)