A Study to Evaluate AMG 133 in Participants With Varying Degrees of Hepatic Impairment or Normal Hepatic Function

A Phase 1, Open-label, Single-Dose Study to Evaluate the Pharmacokinetics of AMG 133 in Participants With Varying Degrees of Hepatic Impairment or Normal Hepatic Function

The primary objective of the trial is to evaluate the pharmacokinetics (PK) of AMG 133 after a single subcutaneous (SC) dose in participants with mild, moderate, or severe hepatic impairment compared to participants with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: AMG 133

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33172
      • Clinical Pharmacology of Miami, LLC
    • Miami Lakes, Florida, United States, 33014-2811
      • Panax Clinical Research
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215-2100
      • The Texas Liver Institute, Inc.
    • San Antonio, Texas, United States, 78229-4801
      • Pinnacle Clinical Research San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults 18 to 75 years of age, male or female.
2. Body mass index ≥ 22 kg/m^2 at screening.

3. For participants with normal hepatic function:

   • In good health with no clinically significant findings from medical history, physical exam, electrocardiogram (ECG), vital signs, or laboratory tests.
   • Systolic blood pressure (BP) 90-150 mmHg and diastolic BP 50-100 mmHg; pulse 40-110 bpm.
   • Stable body weight (< 5 kg change) and no recent dietary modifications within 3 months.

4. For participants with hepatic impairment:

   • Documented Child-Pugh Class A (mild), B (moderate), or C (severe) hepatic impairment.
   • Clinically stable chronic liver disease (e.g., cirrhosis, hepatitis B, alcoholic liver disease, or stable hepatitis C).
   • Systolic BP ≤ 170 mmHg and diastolic BP ≤ 100 mmHg.
5. Willing to use reliable contraception (if of childbearing potential) or practice abstinence through 16 weeks after dosing.

Exclusion Criteria:

1. Any unstable medical condition (e.g., recent hospitalization or major surgery).
2. History of acute or chronic pancreatitis within 1 year or lipase/amylase > 2× ULN at screening.
3. Endocrine disorder that can cause obesity (e.g., Cushing's syndrome).
4. Significant cardiac conditions (e.g., clinically meaningful arrhythmias, 2nd/3rd-degree AV block, QT Interval Corrected Using Fridericia's Formula (QTcF) >450 msec men / >470 msec women for normal hepatic group; > 490 msec men / > 500 msec women for hepatic impairment).
5. Estimated glomerular filtration rate < 60 mL/min/1.73 m^2 (normal/mild) or < 50 mL/min/1.73 m^2 (moderate/severe impairment).
6. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.
7. Uncontrolled thyroid disease or clinically significant gastroparesis.
8. Prior bariatric surgery within 6 months.
9. Poor venous access.
10. Positive Human Immunodeficiency Virus (HIV) test.
11. Hypersensitivity to AMG 133 or its components.
12. Current use of GLP-1 or GIP receptor agents within 3 months.
13. Pregnancy or lactation, or unwillingness to follow contraception requirements.
14. History of substance or alcohol abuse within 1 year or current alcohol intake > 21 units/week (men) or > 14 units/week (women).
15. Positive test for hepatitis B surface antigen or active hepatitis C (with unstable disease).
16. Diabetes mellitus not meeting glycemic cutoffs (hemoglobin A1C ≥ 6.5 % for normal hepatic group or > 11 % for hepatic impairment group).
17. Active malignancy (within 18 months for hepatic impairment group; within 5 years for normal hepatic group).
18. Hepatic encephalopathy Grade ≥ 3 (uncontrolled) or severe uncontrolled ascites.
19. Organ transplant recipients or those on immunosuppressants.
20. Participation in another clinical trial within 30 days or 5 drug half-lives (whichever is longer).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1, AMG 133: Normal Hepatic Function (No Impairment); Participants with normal hepatic function will receive a single dose of AMG 133 SC on Day 1.	Drug: AMG 133; Participants will receive AMG 133 SC.
Experimental: Group 2, AMG-133: Child-Pugh A (Mild Hepatic Impairment); Participants with mild hepatic impairment will receive a single dose of AMG 133 SC on Day 1.	Drug: AMG 133; Participants will receive AMG 133 SC.
Experimental: Group 3, AMG-133: Child-Pugh B (Moderate Hepatic Impairment); Participants with moderate hepatic impairment will receive a single dose of AMG 133 SC on Day 1.	Drug: AMG 133; Participants will receive AMG 133 SC.
Experimental: Group 4, AMG-133: Child-Pugh C (Severe Hepatic Impairment); Participants with severe hepatic impairment will receive a single dose of AMG 133 SC on Day 1.	Drug: AMG 133; Participants will receive AMG 133 SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of AMG 133	Up to Day 120
Area Under the Plasma Concentration-time Curve (AUC) from Time Zero to Time of Last Quantifiable Concentration (AUClast) of AMG 133	Up to Day 120
AUC from Time Zero to Infinity (AUCinf) of AMG 133	Up to Day 120

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)	Up to Day 120
Number of Participants Who Experience Serious Adverse Events (SAEs)	Up to Day 120
Number of Participants Who Develop Anti-AMG 133 Antibodies	Up to Day 120

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2025
• Primary Completion (Actual): February 26, 2026
• Study Completion (Actual): February 26, 2026

Study Registration Dates

• First Submitted: February 19, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 20240024

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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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