Single and Multiple Ascending Dose Study of AMG 133 in Participants With Obesity

NCT04478708 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20180048
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 3

Brief Summary

The study aims to assess the safety and tolerability of maridebart cafraglutide as single and multiple doses in participants with obesity

Conditions

Obesity

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  A TEAE was defined as any adverse event (AE) which started on or after the first dose of AMG 133. Clinically significant changes in laboratory safety tests, vital signs and 12-lead electrocardiograms (ECGs) were included as AEs.

  Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days

Secondary Outcomes (7)

• Part A: Maximum Observed Concentration (Cmax) of AMG 133

  Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150

• Part B: Cmax of AMG 133

  Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207

• Part A: Time of Maximum Observed Concentration (Tmax) of AMG 133

  Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150

• Part B: Tmax of AMG 133

  Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 61, 63, 71, 78, 85, 127, 169 and 207. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 36, 43, 50, 57 (predose), 63, 71, 78, 85, 169 and 207

• Part A: Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of AMG 133

  Cohort 1-5, 11: Day 1 predose and 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 7, 8, 15, 22, 29, 43, 57, 71, 92, 120 and 150. Cohort 6: Day 1 predose and 10 mins, 1, 2, 4 and 8 hours postdose, Day 2, 3, 4, 5, 6, 15, 22, 29, 43, 57, 71, 92, 120 and 150

Study Arms (5)

Part A: maridebart cafraglutide

EXPERIMENTAL

Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11).

Biological: maridebart cafraglutide

Part A: Placebo

PLACEBO COMPARATOR

Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11).

Drug: Placebo

Part B: maridebart cafraglutide

EXPERIMENTAL

Up to 4 multiple ascending dose cohorts (cohorts 7 to 10).

Biological: maridebart cafraglutide

Part B: Placebo

PLACEBO COMPARATOR

Up to 4 multiple ascending dose cohorts (cohorts 7 to 10).

Drug: Placebo

Part C: maridebart cafraglutide

EXPERIMENTAL

Up to 2 open-label, multiple ascending dose cohorts (cohorts 12 to 13) treated with doses previously studied in Part A and Part B.

Biological: maridebart cafraglutide

Interventions

maridebart cafraglutide BIOLOGICAL

Participants will receive maridebart cafraglutide as a single dose in Part A and multiple doses in Part B and C.

Part A: maridebart cafraglutide; Part B: maridebart cafraglutide; Part C: maridebart cafraglutide

Placebo DRUG

Participants will receive placebo as a single dose in Part A and multiple doses in Part B.

Part A: Placebo; Part B: Placebo

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.
• Age ≥ 18 years to ≤ 65 years, at the time of signing the informed consent.
• Except for obesity, otherwise healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and ECGs on day -2 (cohorts 1-6, cohort 11-13) or day -1 (cohorts 7-10) and screening.
• Body mass index between ≥ 30.0 kg/m\^2 and ≤ 40.0 kg/m\^2.
• Have a stable body weight (\< 5 kg self-reported change during the previous 8 weeks) before screening.
• Willing to maintain current general diet and physical activity regimen, except for the physical activity in the 72 hours before each blood sample collection for the clinical laboratory analysis, which should not be strenuous.
• Females must be of nonreproductive potential
• Postmenopausal as defined as:
• Age of ≥ 55 years with no menses for at least 12 months; OR
• Age \< 55 years with no menses for at least 12 months AND with a follicle-stimulating hormone level \> 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR
• History of hysterectomy; OR
• History of bilateral oophorectomy.
• For patients in cohorts 7-10 only, participants must have a smartphone device with the capability of downloading apps or other digital tools required for this cohort.

You may not qualify if:

• History or clinical evidence of diabetes mellitus, including hemoglobin A1c (HbA1c) \> 6.5% and/or a fasting glucose ≥ 125 mg/dl (6.9 mmol/L) at screening.
• Triglycerides ≥ 5.65 mmol/L (ie, 500 mg/dL) at screening.
• Screening calcitonin ≥ 50 ng/L.
• Hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin levels \> 1.5 times the upper limit of normal (ULN) at screening. If ALT is \> 1.5 x the ULN at screening AND the AST, alkaline phosphatase, and total bilirubin levels are within normal limits, then participant may be eligible for enrollment after a discussion with the medical monitor.
• History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (PTT), international normalized ratio (INR), or platelet count outside of the laboratory's normal reference range at screening. If a single value (PT, PTT, INR, or platelet count) is outside the normal reference range at screening and the participant does not have evidence of any other bleeding or coagulation disorder, then the participant may be eligible for enrollment after a discussion with the medical monitor.
• History of gastrointestinal abnormality that could affect gastrointestinal motility (including small bowel or colonic resection, inflammatory bowel disease, irritable bowel disease, and colon or gastrointestinal tract cancer).
• Participants with a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 or a personal history of nonfamilial medullary thyroid carcinoma.
• Participants with a history of confirmed chronic pancreatitis or idiopathic acute pancreatitis.
• Participants with a history of gall bladder disease (ie, cholelithiasis or cholecystitis) not treated with cholecystectomy.
• Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid stimulating hormone \> 6 mIU/L or \<0.4 mIU/L.
• A corrected QT interval (QTc) at screening of \> 450 msec in males or \> 470 msec in females or history of long QT syndrome.
• Participants with a history of renal impairment or renal disease and/or estimated glomerular filtration rate ≤ 60 mL/min/1.73 m\^2.
• Obesity induced by other endocrinologic disorders (eg, Cushing's Syndrome).
• Previous surgical treatment for obesity (excluding liposuction if performed \>1 year before study entry) and/or participants with recent (within 6 months) or planned endoscopic treatment for obesity.
• History of major depressive disorder.

Sponsors & Collaborators

• Amgen: lead

Study Sites (3)

Anaheim Clinical Trials

Anaheim, California, 92801, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Clinical Pharmacology of Miami, LLC

Miami, Florida, 33014, United States

Location

Related Publications (1)

• Veniant MM, Lu SC, Atangan L, Komorowski R, Stanislaus S, Cheng Y, Wu B, Falsey JR, Hager T, Thomas VA, Ambhaikar M, Sharpsten L, Zhu Y, Kurra V, Jeswani R, Oberoi RK, Parnes JR, Honarpour N, Neutel J, Strande JL. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab. 2024 Feb;6(2):290-303. doi: 10.1038/s42255-023-00966-w. Epub 2024 Feb 5.

  PMID: 38316982 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 21, 2020
• Study Start: August 7, 2020
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: December 10, 2025
• Results First Posted: December 10, 2025

Record last verified: 2025-11

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)