A Study to Evaluate AMG 133 Administered Subcutaneously in Participants With Overweight or Obesity

NCT06976372 | Completed Phase 1 FDA Drug

• 1 other identifier: 20240195
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of this study is to assess the pharmacokinetics (PK) of AMG 133 after multiple subcutaneous (SC) administrations in participants with overweight or obesity using various dose regimens.

Conditions

Overweight; Obesity

Keywords

Overweight; Obesity; Maridebart cafraglutide; AMG 133

Outcome Measures

Primary Outcomes (4)

• Maximum Concentration (Cmax) of AMG 133

  Up to Day 99

• Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of AMG 133

  Day 29

• Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of AMG 133

  Day 29

• Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUCtau) of AMG 133

  Day 1 and Day 15

Secondary Outcomes (3)

• Number of Participants Who Experience Treatment-emergent Adverse Events

  Up to Day 99

• Number of Participants Who Experience Serious Adverse Events

  Up to Day 99

• Number of Participants Who Develop Anti-AMG 133 Antibodies

  Up to Day 99

Study Arms (3)

AMG 133 Dose A

EXPERIMENTAL

Participants will receive AMG 133 Dose A SC, followed by subsequent doses of Dose C and Dose D.

Drug: AMG 133

AMG 133 Dose B

EXPERIMENTAL

Participants will receive AMG 133 Dose B SC, followed by subsequent doses of Dose C and Dose D.

Drug: AMG 133

AMG 133 Dose C

EXPERIMENTAL

Participants will receive AMG 133 Dose C SC, followed by subsequent doses of Dose C and Dose D.

Drug: AMG 133

Interventions

AMG 133 DRUG

AMG 133 will be administered SC. Dose levels range from A to D lowest to highest.

AMG 133 Dose A; AMG 133 Dose B; AMG 133 Dose C

Eligibility Criteria

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

You may qualify if:

• Participant has provided informed consent before initiation of any study-specific activities/procedures.
• Male or female participants, between 18 and 65 years of age (inclusive) at the time of Screening.
• Except for obesity, no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia \[e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) as assessed by the Investigator (or designee). Participants with obstructive sleep apnea, controlled hypertension, and/or controlled dyslipidemia on stable therapies will be permitted. Participants with other mild, well-controlled comorbidities may be permitted with approval of the Investigator (or designee) in consultation with the Medical Monitor as appropriate.
• Body mass index ≥ 27 kg/m\^2 at the time of Screening.
• Have a stable body weight (\< 5 kg self-reported change) within 3 months before Screening, as assessed by the Investigator (or designee) based on participant self-report. Have not modified diet or adopted any nutritional lifestyle modification for 3 months, as assessed by the Investigator (or designee) based on participant self-report.

You may not qualify if:

• History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
• History of or active diabetes (regardless of type with the exception of gestational diabetes), or Hemoglobin A1C ≥ 6.5% (≥ 48 mmol/mol), at Screening.
• History or evidence of endocrine disorder (such as Cushing's Syndrome) that can cause obesity.
• History of acute or chronic pancreatitis within 1 year prior to Check-in, or elevation in serum lipase/amylase (\> 2x the upper limit of normal) at Screening, or fasting serum triglyceride level of \> 500 mg/dL at Screening. One repeat of abnormal values will be allowed.
• Malignancy except nonmelanoma skin cancers or cervical or breast ductal carcinoma in situ within the last 5 years.
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
• Uncontrolled thyroid disease, defined as thyroid-stimulating hormone (TSH) \> 6.0 mIU/L or \< 0.4 mIU/L at Screening. Participants who receive treatment for hypothyroidism are permitted if their thyroid hormone replacement dose has been stable for 3 months prior to Screening and TSH criteria are met.
• History of or current signs of gastroparesis.
• Previous surgical procedure for obesity within 6 months prior to Check-in.
• History or current signs or symptoms of cardiovascular disease (aside from controlled hypertension and controlled dyslipidemia), including but not limited to myocardial infarction, congenital heart disease, valvular heart disease, coronary revascularization, or angina.
• History or evidence of clinically significant arrhythmia at Screening, including any clinically significant findings on the ECG taken at Screening or Check-in.
• History of hypersensitivity or allergy to AMG 133 or its ingredients, unless approved by the Investigator (or designee) and in consultation with the Sponsor.
• Estimated glomerular filtration rate less than ≤ 60 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease equation at Screening or Check-in. One repeat of abnormal values will be allowed.
• Alanine aminotransferase or aspartate aminotransferase \> 2x the upper limit of normal at Screening or Check-in. One repeat of abnormal values will be allowed.
• History of or current suicidal ideation (thoughts), suicide attempt(s), or major psychiatric illness (including depression) within 6 months prior to Screening.

Sponsors & Collaborators

• Amgen: lead

Study Sites (3)

CenExel

Anaheim, California, 92801, United States

Location

CenExel Collaborative Neuroscience Research, LLC Los Alamitos

Los Alamitos, California, 90720, United States

Location

Fortrea Clinical Research Unit - Dallas

Dallas, Texas, 75247, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Overweight; Obesity

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: May 16, 2025
• Study Start: August 20, 2024
• Primary Completion: December 27, 2024
• Study Completion: December 27, 2024
• Last Updated: October 8, 2025

Record last verified: 2025-10

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

US (3)