Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus

A Phase 2 Randomized, Placebo-controlled, Double-blind, Dose-ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AMG 133 in Adult Subjects With Overweight or Obesity, With or Without Type 2 Diabetes Mellitus

The study aims to compare and assess the dose response of 3 selected doses of maridebart cafraglutide compared with placebo, on inducing and maintaining weight loss from baseline at Week 52 in participants with overweight or obesity without diabetes mellitus (Cohort A) and in participants with overweight or obesity with Type 2 diabetes mellitus (Cohort B).

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Biological: Maridebart Cafraglutide

• Study Type: Interventional
• Enrollment (Actual): 592
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2006
      • Royal Prince Alfred Hospital (RPAH) Clinic
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Clinical Medical and Analytical eXellence CMAX
  • Victoria
    • Clayton, Victoria, Australia, 3146
      • Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
    • Heidelberg Heights, Victoria, Australia, 3081
      • Austin Health, Heidelberg Repatriation Hospital
    • Melbourne, Victoria, Australia, 3004
      • Baker Heart and Diabetes Institute
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • University of Calgary
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • Centricity Research Brampton Endocrinology
    • Concord, Ontario, Canada, L4K 4M2
      • Centricity Research Vaughan Endocrinology
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Institut universitaire de Cardiologie et de Pneumologie de Quebec
    • Québec, Quebec, Canada, G1V 4W2
      • Clinique des Maladies Lipidiques de Quebec Incorporated
• Czechia
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
  • Prague, Czechia, 140 21
    • Institut klinicke a experimentalni mediciny
  • Prague, Czechia, 116 94
    • Endokrinologicky ustav
• Germany
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin, Campus Mitte
  • Hamburg, Germany, 22607
    • Diabeteszentrum Hamburg West
  • Leipzig, Germany, 04103
    • Universitaetsmedizin Leipzig
• Hong Kong
  • Shatin, New Territories, Hong Kong
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1021
    • Budapesti Szent Ferenc Korhaz
  • Budapest, Hungary, 1033
    • Clinexpert Kft
  • Encs, Hungary, 3860
    • CRU Hungary Kft
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont
• Japan
  • Ehime
    • Matsuyama, Ehime, Japan, 790-0034
      • Mikannohana Clinic, Diabetes, Endocrinology and Metabolism
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 810-0001
      • Wellness Tenjin Clinic
  • Gifu
    • Hashima-gun, Gifu, Japan, 501-6061
      • Matsunami Health Promotion Clinic
  • Hiroshima
    • Aki-gun, Hiroshima, Japan, 735-8585
      • Mazda Hospital of Mazda Motor Corporation
  • Ibaraki
    • Naka, Ibaraki, Japan, 311-0113
      • Nakakinen clinic
    • Naka, Ibaraki, Japan, 311-0133
      • Nishiyamado Keiwa Hospital
  • Osaka
    • Kashiwara-shi, Osaka, Japan, 582-0005
      • Shiraiwa Medical Clinic
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 103-0025
      • Nihonbashi Sakura Clinic
    • Shibuya-ku, Tokyo, Japan, 151-0051
      • Mih Clinic Yoyogi
• Poland
  • Bydgoszcz, Poland, 85-752
    • AthleticoMed
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House Spzoo
  • Lodz, Poland, 90-338
    • Centrum Terapii Wspolczesnej
  • Lodz, Poland, 90-349
    • AppleTreeClinics Network Spzoo
  • Lublin, Poland, 20-078
    • Clinical Best Solutions Sp zoo Spolka komandytowa
  • Wroclaw, Poland, 52-210
    • MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak
• South Korea
  • Goyang-si, Gyeonggi-do, South Korea, 10326
    • Dongguk University Ilsan Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seongnam-si, Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
• Spain
  • Andalusia
    • Castilleja de la Cuesta, Andalusia, Spain, 41950
      • Hospital Vithas Sevilla
    • Málaga, Andalusia, Spain, 29010
      • Hospital Clinico Universitario Virgen de La Victoria
  • Catalonia
    • Lleida, Catalonia, Spain, 25198
      • Hospital Universitario Arnau de Vilanova Lleida
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Complexo Hospitalario Universitario A Coruña
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Alliance for Multispecialty Research Mobile
  • Arizona
    • Phoenix, Arizona, United States, 85044
      • Foothills Research Center
    • Scottsdale, Arizona, United States, 85258
      • Honorhealth
  • California
    • Long Beach, California, United States, 90815
      • Ark Clinical Research- Long Beach
    • Tustin, California, United States, 92780
      • Orange County Research Center
    • Tustin, California, United States, 92780
      • Ark Clinical Research- Tustin
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Alliance for Multispecialty Research Miami
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Kansas
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research Newton
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • Louisville Metabolic and Atherosclerosis Research Center
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research - Marrero
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research Kansas City
  • New York
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Research Innovations LLC dba Internal Medicine Care Inc
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance for Multispecialty Research Norman
  • Tennessee
    • Elizabethton, Tennessee, United States, 37643
      • Medical Care LLC
  • Texas
    • Brownsville, Texas, United States, 78520
      • PanAmerican Clinical Research LLC
    • Brownsville, Texas, United States, 78526
      • Headlands Research Brownsville
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78229
      • Diabetes and Glandular Disease Clinic
    • San Antonio, Texas, United States, 78284
      • Texas Diabetes Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years at the time of signing informed consent.
• BMI ≥30 kg/m^2, or ≥27 kg/m^2 and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease.
• For participants in cohort B only, HbA1c ≥ 7% and ≤ 10% (53 to 86 mmol/mol) at screening with an established diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening and either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sulfonylurea, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor as monotherapy or combination therapy, per approved local label.
• History of at least one unsuccessful dietary effort to lose body weight.

Exclusion Criteria:

• Change in body weight greater than 5 kg within 3 months prior to screening.
• Obesity induced by other endocrinologic disorders.
• History of pancreatitis.
• Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).
• History of major depressive disorder within the last 2 years.
• Any lifetime history of other major psychiatric disorder or suicide attempt.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Maridebart Cafraglutide; Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.	Drug: Placebo; Participants will receive placebo by SC injection.; Biological: Maridebart Cafraglutide; Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.; Other Names: AMG 133
Placebo Comparator: Cohort A: Placebo; Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts . Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.	Drug: Placebo; Participants will receive placebo by SC injection.; Biological: Maridebart Cafraglutide; Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.; Other Names: AMG 133
Experimental: Cohort B: Maridebart Cafraglutide; Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.	Drug: Placebo; Participants will receive placebo by SC injection.; Biological: Maridebart Cafraglutide; Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.; Other Names: AMG 133
Placebo Comparator: Cohort B: Placebo; Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.	Drug: Placebo; Participants will receive placebo by SC injection.; Biological: Maridebart Cafraglutide; Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.; Other Names: AMG 133

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent Change From Baseline to Week 52 in Body Weight	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ≥ 5% Reduction in Body Weight From Baseline at Week 52		Baseline and Week 52
Percentage of Participants Achieving ≥ 10% Reduction in Body Weight From Baseline at Week 52		Baseline and Week 52
Change from Baseline to Week 52 in Hemoglobin A1c (HbA1c)		Baseline and Week 52
Change from Baseline to Week 52 in Fasting Serum Insulin		Baseline and Week 52
Change from Baseline to Week 52 in Fasting Plasma Glucose		Baseline and Week 52
Change from Baseline to Week 52 in Homeostasis Model Assessment for Insulin Resistance (HOMA2-IR)		Baseline and Week 52
Change from Baseline to Week 52 in Homeostasis Model Assessment for Steady State Beta Cell Function (HOMA2-%B)		Baseline and Week 52
Change from Baseline to Week 52 in Waist Circumference		Baseline and Week 52
Change from Baseline to Week 52 in Body Weight		Baseline and Week 52
Change from Baseline to Week 52 in Systolic Blood Pressure (SBP)		Baseline and Week 52
Change from Baseline to Week 52 in Diastolic Blood Pressure (DBP)		Baseline and Week 52
Change from Baseline to Week 52 in Lean Body Mass Using DEXA	Analyzed in a subset of participants.	Baseline and Week 52
Change from Baseline to Week 52 in Body Mass Index (BMI)		Baseline and Week 52
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)		Baseline and Week 52
Percent Change From Baseline in Total Cholesterol		Baseline and Week 52
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)		Baseline and Week 52
Percent Change From Baseline in non-HDL-C		Baseline and Week 52
Percent Change From Baseline in Very-low-density Lipoprotein Cholesterol (VLDL-C)		Baseline and Week 52
Percent Change From Baseline in Triglycerides		Baseline and Week 52
Percent Change From Baseline in Free Fatty Acids (FFA)		Baseline and Week 52
Percent Change From Baseline to Week 52 in High-sensitivity C-reactive Protein (hs-CRP)		Baseline and Week 52
Achievement of ≥ 15% Reduction in Body Weight From Baseline at Week 52		Baseline and Week 52
Achievement of ≥ 20% Reduction in Body Weight From Baseline at Week 52		Baseline and Week 52
Change from Baseline to Week 52 in Body Fat Mass Using Dual-energy X-ray Absorptiometry (DEXA)	Analyzed in a subset of participants.	Baseline and Week 52
Maximum Observed Plasma Concentration (Cmax) of maridebart cafraglutide		Up to Week 64
Area Under the Concentration-time Curve (AUC) of maridebart cafraglutide		Up to Week 64

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Jastreboff AM, Ryan DH, Bays HE, Ebeling PR, Mackowski MG, Philipose N, Ross L, Liu Y, Burns CE, Abbasi SA, Pannacciulli N; MariTide Phase 2 Obesity Trial Investigators. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial. N Engl J Med. 2025 Sep 4;393(9):843-857. doi: 10.1056/NEJMoa2504214. Epub 2025 Jun 23.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2023
• Primary Completion (Actual): October 8, 2024
• Study Completion (Actual): December 16, 2025

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: December 20, 2022
• First Posted (Actual): January 3, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 20190218; 2023-510470-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No