Evaluation of Maridebart Cafraglutide Efficacy and Safety in Adults with Obesity or Overweight Without Type 2 Diabetes Mellitus: A Phase 3 Randomized, Double-blind, Placebo-controlled Study
- Trial ID
- 2024-515524-36-00
- Protocol
- 20210181
- Sponsor
- Amgen Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 randomized, double-blind, placebo-controlled study is to evaluate the efficacy of **maridebart cafraglutide** in achieving a superior percentage change in body weight compared to placebo in adult participants without Type 2 Diabetes Mellitus who have obesity or are overweight. This objective is clinically relevant as it addresses chronic weight management, a significant health concern associated with various comorbidities.
Secondary objectives include demonstrating the superiority of maridebart cafraglutide over placebo in:
- Reduction in central adiposity
- Reduction in body weight
- Reduction in systolic blood pressure
- Reduction in triglycerides
- Improvement in glycemia
- Improvement in functional health and well-being
These secondary objectives aim to provide a comprehensive assessment of the potential benefits of maridebart cafraglutide beyond weight reduction, addressing various metabolic and cardiovascular risk factors associated with obesity.
Participants
The clinical trial for **chronic weight management** involves a total of 2,451 participants, comprising both male and female subjects. The study population includes adults aged 18 years and older, with a **body mass index (BMI)** of 30 kg/m² or higher, or a BMI between 27 and less than 30 kg/m² accompanied by at least one weight-related comorbidity such as hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease, or metabolic dysfunction-associated steatotic liver disease. Participants were selected based on their history of at least one unsuccessful attempt at weight loss through diet and exercise. The trial does not include vulnerable populations. Participants are expected to be well-motivated and willing to adhere to study procedures, including following lifestyle advice and maintaining lifestyle logs. The trial aims to evaluate the efficacy of maridebart cafraglutide compared to a placebo in achieving a percentage change in body weight.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy, safety, and tolerability of **maridebart cafraglutide** in adult participants without type 2 diabetes mellitus who have obesity or are overweight. The primary objective is to demonstrate that maridebart cafraglutide is superior to placebo in terms of percentage change in body weight. The trial is set to last for a total duration of 72 weeks, with the estimated recruitment start date being May 27, 2025, and the estimated end date being April 16, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, body mass index (BMI), and history of weight loss attempts. The inclusion criteria require participants to be at least 18 years old, have a BMI of ≥30 kg/m², or a BMI of 27 to <30 kg/m² with at least one weight-related comorbidity. Following the screening, participants will be randomized to receive either maridebart cafraglutide or a placebo, both administered as a **solution for injection** via subcutaneous use.
Throughout the trial, participants will attend regular follow-up visits to monitor changes in body weight, waist circumference, blood pressure, fasting triglycerides, and fasting glucose. The primary endpoint is the percent change from baseline in body weight at week 72. Secondary endpoints include changes in waist circumference, achieving specific weight reduction milestones, and changes in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score.
The expected length of participant involvement is the full 72 weeks unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent. Participants are expected to adhere to study procedures, including lifestyle advice and maintaining lifestyle logs. The trial is not classified as a low-intervention study, and it is conducted under the sponsorship of Amgen Inc. The study aims to provide valuable insights into the management of chronic weight conditions in the specified population.
Treatment
The clinical trial involves the administration of **AMG 133**, an experimental medication, which is a **solution for injection**. The active substance in AMG 133 is **maridebart cafraglutide**, a protein-based compound classified as a human IgG1 monoclonal antibody against the gastric inhibitory polypeptide receptor, fused to a glucagon-like peptide 1 analog. The pharmaceutical form of AMG 133 is a solution intended for **subcutaneous use**. The dosing schedule allows for a maximum daily dose of 9999 mg, with a total treatment period not exceeding 72 weeks. The administration of AMG 133 is monitored to ensure participant compliance, and the medication is provided by Amgen Inc.
The study also includes a **placebo** group, where participants receive a placebo designed to mimic the administration of maridebart cafraglutide. The placebo is administered in the same pharmaceutical form and route as AMG 133, ensuring the double-blind nature of the trial. The placebo is used to evaluate the efficacy, safety, and tolerability of maridebart cafraglutide by providing a comparator for the experimental treatment. The placebo does not contain any active substance and is used to maintain the integrity of the study's blinding process.
Efficacy
The efficacy of Maridebart Cafraglutide in the clinical trial will be assessed primarily through the **percent change from baseline in body weight** at week 72. This primary endpoint is designed to demonstrate the superiority of Maridebart Cafraglutide over placebo in achieving weight reduction in adult participants without Type 2 Diabetes Mellitus who have obesity or are overweight. Secondary endpoints include several additional measures at week 72: change from baseline in waist circumference, achieving reductions in body weight of 5%, 10%, 15%, and 20% from baseline, change from baseline in systolic blood pressure (SBP), percent change from baseline in fasting triglycerides, change from baseline in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function Composite Score, and change from baseline in fasting glucose.
These efficacy parameters will be collected and analyzed at the specified timepoint of week 72. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable measurement of these endpoints. The data collected will be analyzed to determine the effectiveness of Maridebart Cafraglutide in achieving the desired outcomes compared to placebo, providing insights into its potential benefits for weight management in the specified population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant has provided informed consent before initiation of any study-specific ctivities/procedures.
- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
- BMI ≥ 30 kg/m2 at screening, OR BMI ≥ 27 to < 30 kg/m2 at screening, with at least 1 of the following weight-related comorbidities: * hypertension: treated, or with SBP ≥ 130 mmHg or DBP ≥ 80 mmHg * dyslipidemia: treated, or with: LDL ≥ 160 mg/dL (4.1 mmol/L), or triglycerides ≥ 150 mg/dL (1.7 mmol/L), or HDL < 40 mg/dL (1.0 mmol/L) for males or HDL < 50 mg/dL (1.3 mmol/L) for females * obstructive sleep apnea * cardiovascular disease (for example, ischemic cardiovascular disease, New York Heart Association (NYHA) Class I, II, or III heart failure) * metabolic dysfunction-associated steatotic liver disease
- History of at least 1 unsuccessful attempt at weight loss by diet and exercise
- In the opinion of the investigator, well-motivated and willing to follow study procedures for the duration of the study, including, but not limited to: following lifestyle advice, maintaining lifestyle log(s), and completing required study visits and questionnaires
Exclusion Criteria
- Obesity induced by other endocrinologic disorders, monogenetic or syndromic forms of obesity
- Self-reported change in body weight > 5kg 90 days before screening
- Previous or planned surgical, endoscopic, or device-based treatment for obesity
- History of malignancy 5 years before screening
- Type 1 or 2 diabetes mellitus or any other types of diabetes mellitus
- History of chronic pancreatitis
- History of acute pancreatitis 180 days before screening
- Family or personal history of MTC or multiple endocrine neoplasia syndrome type 2
- History of the following 60 days before screening: myocardial infarction, coronary artery bypass graft surgery or other major cardiovascular surgery, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack
- New York Heart Association Class IV heart failure
- History of unstable major depressive disorder or other severe psychiatric disorder 2 years before screening
- History of organ transplant or on transplant list
- History of other conditions that the investigator, may preclude the participant from following the protocol and completing the study
- Clinically significant gastric-emptying abnormality
- Use 90 days before randomization of medications, supplements, or alternative remedies for weight loss
- Use 90 days before randomization of glucose-lowering drugs for the treatment of diabetes
- Use 90 days before randomization or require use during the trial of medications that may cause significant weight gain including, but not limited to chronic systemic glucocorticoid therapy, tricyclic antidepressants, atypical tetracyclic antidepressants, atypical antipsychotics, lithium, and all formulations of valproic acid
- Is receiving treatment in another investigational device or drug study, or within 90 days since ending treatment on another investigational device or drug study. This does not apply to other investigational procedures or participation in observational research studies
- Participation in a study that includes maridebart cafraglutide or AMG 598
- Hemoglobin A1c ≥ 6.5% & fasting plasma glucose ≥ 126 mg/dL at screening. If only 1 of the above labs meets the threshold at screening, then the participant should be retested for both & excluded if any repeated test result meets the threshold
- Estimated glomerular filtration rate < 30 mL/min/1.73 m2 according to 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation or receiving dialysis at screening
- Calcitonin ≥ 50 ng/L at screening
- Thyroid-stimulating hormone < 0.4 mIU/L or TSH > 6.0 mIU/L with free thyroxine below the lower limit of normal at screening
- Acute or chronic hepatitis, signs & symptoms of any liver disease other than MASLD, ALT > 3.0 x the upper limit of normal, or total bilirubin > 1.2 x ULN
- Systolic blood pressure ≥ 180 mmHg and/or DBP ≥ 120 mmHg at screening
- Patient Health Questionnaire-9 score of ≥ 15 on day 1 before randomization
- Suicidal ideation of category 4 or 5 on the Columbia-Suicide Severity Rating Scale Baseline version at screening, or on the C-SSRS Since Last Visit version on day 1 before randomization
- History of suicide attempt evaluated through C-SSRS Baseline version at screening or any suicidal behavior on the C-SSRS Since Last Visit version on day 1 before randomization
- Participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment & the 16 weeks after last dose of investigational product
- Participants who are breastfeeding or plan to breastfeed while on study through 16 weeks after last dose of investigational product
- Participants planning to become pregnant while on study and 16 weeks after the last dose of investigational product
- Participants of childbearing age with a positive pregnancy test assessed at screening and/or day 1 before randomization
- Any disorder, unwillingness, or inability, not covered by the other exclusion criteria, that in the investigator’s opinion, might jeopardize the participant’s safety or compliance with the protocol
- Major surgery planned during the study
- Investigative site personnel directly affiliated with the study and/or their immediate family
- Participant has known sensitivity to any of the products or components to be administered during dosing
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 27 May 2025 | 59 |
 Czechia | Not Recruiting | 27 May 2025 | 94 |
 Denmark | Not Recruiting | 27 May 2025 | 77 |
 Finland | Not Recruiting | 27 May 2025 | 50 |
 Germany | Not Recruiting | 27 May 2025 | 473 |
 Italy | Not Recruiting | 27 May 2025 | 20 |
 Poland | Not Recruiting | 27 May 2025 | 179 |
 Spain | Not Recruiting | 27 May 2025 | 108 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AMG 133 | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 9999 | 72 | PRD10000277 |
Placebo for Maridebart Cafraglutide | Placebo | N/A | — | — | — | N/A |