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

NCT05669599 | Completed Phase 2 FDA Drug

• 2 other identifiers: 201902182023-510470-13-00
• Study Type: interventional
• Target: 592
• Locations: 12 countries
• Sites: 78

Brief Summary

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).

Conditions

Obesity; Overweight; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to Week 52 in Body Weight

  Baseline and Week 52

Secondary Outcomes (26)

• 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

• 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 Hemoglobin A1c (HbA1c)

  Baseline and Week 52

Study Arms (4)

Cohort A: Maridebart Cafraglutide

EXPERIMENTAL

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.

Biological: Maridebart Cafraglutide; Drug: Placebo

Cohort A: Placebo

PLACEBO COMPARATOR

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.

Biological: Maridebart Cafraglutide; Drug: Placebo

Cohort B: Maridebart Cafraglutide

EXPERIMENTAL

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.

Biological: Maridebart Cafraglutide; Drug: Placebo

Cohort B: Placebo

PLACEBO COMPARATOR

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.

Biological: Maridebart Cafraglutide; Drug: Placebo

Interventions

Maridebart Cafraglutide BIOLOGICAL

Participants will receive maridebart cafraglutide by subcutaneous (SC) injection.

Also known as: AMG 133

Cohort A: Maridebart Cafraglutide; Cohort A: Placebo; Cohort B: Maridebart Cafraglutide; Cohort B: Placebo

Placebo DRUG

Participants will receive placebo by SC injection.

Cohort A: Maridebart Cafraglutide; Cohort A: Placebo; Cohort B: Maridebart Cafraglutide; Cohort B: Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (78)

Alliance for Multispecialty Research Mobile

Mobile, Alabama, 36608, United States

Location

Foothills Research Center

Phoenix, Arizona, 85044, United States

Location

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Ark Clinical Research- Long Beach

Long Beach, California, 90815, United States

Location

Ark Clinical Research- Tustin

Tustin, California, 92780, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

Alliance for Multispecialty Research Miami

Coral Gables, Florida, 33134, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

East-West Medical Research

Honolulu, Hawaii, 96814, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Alliance for Multispecialty Research Newton

Newton, Kansas, 67114, United States

Location

Louisville Metabolic and Atherosclerosis Research Center

Louisville, Kentucky, 40213, United States

Location

Tandem Clinical Research - Marrero

Marrero, Louisiana, 70072, United States

Location

StudyMetrix Research

City of Saint Peters, Missouri, 63303, United States

Location

Alliance for Multispecialty Research Kansas City

Kansas City, Missouri, 64114, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Research Innovations LLC dba Internal Medicine Care Inc

Beavercreek, Ohio, 45431, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Alliance for Multispecialty Research Norman

Norman, Oklahoma, 73069, United States

Location

Medical Care LLC

Elizabethton, Tennessee, 37643, United States

Location

PanAmerican Clinical Research LLC

Brownsville, Texas, 78520, United States

Location

Headlands Research Brownsville

Brownsville, Texas, 78526, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

Diabetes and Glandular Disease Clinic

San Antonio, Texas, 78229, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Texas Diabetes Institute

San Antonio, Texas, 78284, United States

Location

Royal Prince Alfred Hospital (RPAH) Clinic

Camperdown, New South Wales, 2006, Australia

Location

Clinical Medical and Analytical eXellence CMAX

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3146, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Austin Health, Heidelberg Repatriation Hospital

Heidelberg Heights, Victoria, 3081, Australia

Location

Baker Heart and Diabetes Institute

Melbourne, Victoria, 3004, Australia

Location

University of Calgary

Calgary, Alberta, T2T 5C7, Canada

Location

Centricity Research Brampton Endocrinology

Brampton, Ontario, L6S 0C6, Canada

Location

Centricity Research Vaughan Endocrinology

Concord, Ontario, L4K 4M2, Canada

Location

Institut Universitaire de cardiologie et de pneumologie de Quebec

Québec, Quebec, G1V 4G5, Canada

Location

Clinique des Maladies Lipidiques de Quebec Incorporated

Québec, Quebec, G1V 4W2, Canada

Location

Endokrinologicky ustav

Prague, 116 94, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Institut klinicke a experimentalni mediciny

Prague, 140 21, Czechia

Location

Charite - Universitaetsmedizin Berlin, Campus Mitte

Berlin, 10117, Germany

Location

Diabeteszentrum Hamburg West

Hamburg, 22607, Germany

Location

Universitaetsmedizin Leipzig

Leipzig, 04103, Germany

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Budapesti Szent Ferenc Korhaz

Budapest, 1021, Hungary

Location

Clinexpert Kft

Budapest, 1033, Hungary

Location

CRU Hungary Kft

Encs, 3860, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7624, Hungary

Location

Mikannohana Clinic, Diabetes, Endocrinology and Metabolism

Matsuyama, Ehime, 790-0034, Japan

Location

Wellness Tenjin Clinic

Fukuoka, Fukuoka, 810-0001, Japan

Location

Matsunami Health Promotion Clinic

Hashima-gun, Gifu, 501-6061, Japan

Location

Mazda Hospital of Mazda Motor Corporation

Aki-gun, Hiroshima, 735-8585, Japan

Location

Nakakinen Clinic

Naka, Ibaraki, 311-0113, Japan

Location

Nishiyamado Keiwa Hospital

Naka, Ibaraki, 311-0133, Japan

Location

Shiraiwa Medical Clinic

Kashiwara-shi, Osaka, 582-0005, Japan

Location

Nihonbashi Sakura Clinic

Chuo-ku, Tokyo, 103-0025, Japan

Location

MIH Clinic Yoyogi

Shibuya-ku, Tokyo, 151-0051, Japan

Location

AthleticoMed

Bydgoszcz, 85-752, Poland

Location

Centrum Badan Klinicznych PI-House Spzoo

Gdansk, 80-546, Poland

Location

Centrum Terapii Wspolczesnej

Lodz, 90-338, Poland

Location

AppleTreeClinics Network Spzoo

Lodz, 90-349, Poland

Location

Clinical Best Solutions Sp zoo Spolka Komandytowa

Lublin, 20-078, Poland

Location

Migre Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak

Wroclaw, 52-210, Poland

Location

Dongguk University Ilsan Hospital

Goyang-si, Gyeonggi-do, 10326, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Hospital Vithas Sevilla

Castilleja de la Cuesta, Andalusia, 41950, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital Universitario Arnau de Vilanova Lleida

Lleida, Catalonia, 25198, Spain

Location

Complexo Hospitalario Universitario A Coruña

A Coruña, Galicia, 15006, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 40549887 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Obesity; Overweight; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 3, 2023
• Study Start: January 18, 2023
• Primary Completion: October 8, 2024
• Study Completion: December 16, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

HK (1); JP (9); PL (6); AU (6); HU (4); TW (4); CA (5); ES (4); KR (4); CZ (3); US (29); DE (3)