ObesityPhase 1NCT04478708

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

A Phase 1 study testing maridebart cafraglutide in people with Obesity, run by Amgen at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Obesity
What is being tested?: maridebart cafraglutide
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 110 participants
Where: 3 sitesUnited States
Study dates: 7 Aug 2020to 18 Nov 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 13Show fewer

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.

Who cannot join

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).

Show all 47Show fewer

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.
History of other severe psychiatric disorders, eg schizophrenia, bipolar disorder.
Any lifetime history of a suicidal attempt or of any suicidal behavior.
Surgery scheduled for the study duration period, except for minor surgical procedures, at the discretion of the investigator.
Positive results for human immunodeficiency virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus RNA. For hepatitis C, hepatitis C antibody testing is done at screening, followed by hepatitis C virus RNA by polymerase chain reaction if hepatitis C antibody is positive.
Systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg at screening, or on day -2. For each visit, if the initial blood pressure is elevated, the reading may be repeated once at least 15 minutes later and the lower of the 2 readings may be used.
History of malignancy of any type, other than in situ cervical cancer or surgically excised nonmelanomatous skin cancers occurring more than 5 years before randomization.
Use of the following agents are excluded unless there is a prior consultation between the investigator and Amgen medical monitor:
Prescription and nonprescription drugs within 14 days or 5 half-lives, whichever is longer, before the first dose of investigational product, with exception of hormone replacement therapy (eg, estrogen, thyroid).
All herbal medicines, vitamins, and supplements within 30 days before receiving the first dose of investigational product.
Exceptions must be reviewed and approved by the investigator and Amgen medical monitor. Written documentation of this review and Amgen acknowledgment is required for participant participation.
Current or history of treatment with medications that may cause significant weight gain or loss, within 3 months before screening, including systemic corticosteroids (except for a short course of treatment, ie, 7 to 10 days), tricyclic antidepressants, atypical antipsychotic and mood stabilizers (eg, imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium).
Current participation (or within the last 3 months) in an organized weight reduction program or currently using or used within 3 months before screening: pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, bupropion, lorcaserin, metformin, or any GLP-1R agonists (either by prescription or as part of a clinical study).
Prior exposure to maridebart cafraglutide or AMG 598 or currently receiving treatment in another investigational device or drug study, or less than 5 half-lives since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
Female participants with a positive pregnancy test assessed at screening and/or day -2 by a serum pregnancy test and/or urine pregnancy test) or female participants who are breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 5 months after the last dose of maridebart cafraglutide.
Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use an acceptable method of contraception during treatment and for an additional 5 months after the last dose of maridebart cafraglutide.
Male participants unwilling to abstain from donating sperm during treatment and for an additional 5 months after the last dose of maridebart cafraglutide.
Participant has known sensitivity to maridebart cafraglutide or components thereof or a history of drug or other allergy that is in the opinion of the investigator or medical monitor (if appropriate), contraindicates their participation.
Participant has a known sensitivity to GLP-1R agonists.
Participant has known sensitivity to mammalian derived products.
Participant has an allergy or known sensitivity to acetaminophen.
Participant is unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol is prohibited 48 hours before day -2 and is limited to no more than to 2 drinks per day for males and 1 drink per day for females for the duration of the study (1 drink being equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits).
Participant uses nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, e-cigarettes, pipes, or nicotine patches) within 6 months before screening. Participant is unwilling or unable to abstain from nicotine or tobacco, cigars, cigarettes, pipes, or nicotine patches throughout the course of the study.
Participant is tested positive for alcohol and/or drugs of abuse at screening.
History of substance abuse (ie, alcohol, licit or illicit drugs) within 12 months before screening.
Participant is unwilling to refrain from strenuous exercise (eg, heavy lifting, weight training, and aerobics) for 72 hours before each blood collection for clinical laboratory tests.
Participant has donated or lost ≥ 500 mL of blood or plasma within 60 days of day -2.
Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
For participants in cohorts 7-10 and cohorts 12-13 only, the Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10 up to day 1.
For participants in cohorts 7-10 and 12-13 only, any suicidal ideation as identified by endorsement of (answered yes to) any of the items numbered 1-5 on the Columbia Suicide Severity Rating Scale (C-SSRS) up to day 1.
For participants in cohorts 7-10 and 12-13 only, participant has systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 95 mm Hg on day 1. For each visit, if the initial blood pressure is elevated, the reading may be repeated once at least 15 minutes later and the lower of the 2 readings may be used.
For participants in cohorts 7-10 and 12-13 only, a QTc of > 450 msec in males or > 470 msec in females up to day 1.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Anaheim Clinical Trials
Anaheim, California, 92801
Clinical Pharmacology of Miami, LLC
Miami, Florida, 33014
Orange County Research Center
Tustin, California, 92780

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 133 in Subjects With Obesity

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

Conditions: Obesity
Being tested: maridebart cafraglutide, Placebo
Medical subject headings: Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04478708
Study group	Role	What they receive
Part A: maridebart cafraglutide	Experimental	Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11). Receives: Biological: maridebart cafraglutide
Part A: Placebo	Placebo comparator	Up to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11). Receives: Drug: Placebo
Part B: maridebart cafraglutide	Experimental	Up to 4 multiple ascending dose cohorts (cohorts 7 to 10). Receives: Biological: maridebart cafraglutide
Part B: Placebo	Placebo comparator	Up to 4 multiple ascending dose cohorts (cohorts 7 to 10). Receives: 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. Receives: Biological: maridebart cafraglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Measured: 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
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported.
Measured: 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
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Measured: 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
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported.
Measured: 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
The pharmacokinetic parameter estimates of intact and total AMG 133 after a single administration of AMG 133 were reported.
Measured: 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: AUC From Day 0 to 28 (AUC0-28) of AMG 133
The pharmacokinetic parameter estimates of intact and total AMG 133 after multiple administrations of AMG 133 were reported.
This parameter shows the AUC over the 28-day dosing interval, both from Day 1 to Day 29 (predose) and from Day 57 to Day 85.
Measured: Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 61, 63, 71, 78 and 85. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 63, 71, 78 and 85
Percentage of Participants With Anti-AMG 133 Antibody Formation
The percentage of participants who developed anti-AMG 133 antibodies (binding and if positive, neutralizing to native GLP-1, when available) at any time was presented.
Measured: Part A Cohort 1-6 and 11: Up to Day 150. Part B Cohort 7-10 and Part C Cohort 13: Up to Day 207. Part C Cohort 12: Up to Day 193

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Aug 202018 Nov 2022

First posted21 Jul 2020
Study start7 Aug 2020
Primary completion18 Nov 2022
Study completion18 Nov 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 110 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04478708
Sponsor's protocol ID: 20180048
Status last verified: Nov 2025
First submitted: 16 Jul 2020
Last updated: 10 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Publications

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.
PubMed 38316982

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
Obesity
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)

All Obesity trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 133 in Subjects With Obesity
ClinicalTrials.gov ID: NCT04478708
Acronym / sponsor ID: 20180048
Conditions: Obesity
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 110 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 7 Aug 2020 (actual)
Primary completion: 18 Nov 2022 (actual)
Study completion: 18 Nov 2022 (actual)
First posted: 21 Jul 2020 (actual)
Results: Posted 10 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 5

Arm	Type	Receives
Part A: maridebart cafraglutide	Experimental	Biological: maridebart cafraglutideUp to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11).
Part A: Placebo	Placebo comparator	Drug: PlaceboUp to 7 single ascending dose cohorts (cohorts 1 to 6 and cohort 11).
Part B: maridebart cafraglutide	Experimental	Biological: maridebart cafraglutideUp to 4 multiple ascending dose cohorts (cohorts 7 to 10).
Part B: Placebo	Placebo comparator	Drug: PlaceboUp to 4 multiple ascending dose cohorts (cohorts 7 to 10).
Part C: maridebart cafraglutide	Experimental	Biological: maridebart cafraglutideUp to 2 open-label, multiple ascending dose cohorts (cohorts 12 to 13) treated with doses previously studied in Part A and Part B.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.

Key exclusion criteria (47 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
maridebart cafraglutideParticipants will receive maridebart cafraglutide as a single dose in Part A and multiple doses in Part B and C.	Biological	Part A: maridebart cafraglutide, Part B: maridebart cafraglutide, Part C: maridebart cafraglutide
PlaceboParticipants will receive placebo as a single dose in Part A and multiple doses in Part B.	Drug	Part A: Placebo, Part B: Placebo

Primary outcome

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days
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.

7 secondary outcomes

Part A: Maximum Observed Concentration (Cmax) of AMG 133
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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: AUC From Day 0 to 28 (AUC0-28) of AMG 133
Time frame: Cohorts 7-9: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 61, 63, 71, 78 and 85. Cohort 10: Day 1 (predose), Day 5, 7, 15, 22, 29 (predose), 57 (predose), 63, 71, 78 and 85
Percentage of Participants With Anti-AMG 133 Antibody Formation
Time frame: Part A Cohort 1-6 and 11: Up to Day 150. Part B Cohort 7-10 and Part C Cohort 13: Up to Day 207. Part C Cohort 12: Up to Day 193

Results and safety

Results posted to the registry on 10 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A SAD Cohort 1 AMG 133	6	6
Part A SAD Cohort 2 AMG 133	6	5
Part A SAD Cohort 3 AMG 133	7	5
Part A SAD Cohort 4 AMG 133	6	6
Part A SAD Cohort 5 AMG 133	6	5
Part A SAD Cohort 6 AMG 133	6	5
Part A SAD SC Placebo (Cohorts 1-5, 11)	12	11
Part A SAD IV Placebo (Cohort 6)	2	2
Part B MAD Cohort 7 AMG 133	6	5
Part B MAD Cohort 8 AMG 133	6	5
Part B MAD Cohort 9 AMG 133	8	3
Part B MAD Cohort 10 AMG 133	10	5
Part B MAD Cohorts 7-9 Placebo	6	5
Part B MAD Cohort 10 Placebo	3	3
Part A SAD Cohort 11 AMG 133	6	5
Part C MAD Cohort 12	6	6
Part C MAD Cohort 13	8	4

Primary outcome: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time frame: Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days. Number. Unit: participants

Measure	Part A SAD Cohort 1 AMG 133 n = 6	Part A SAD Cohort 2 AMG 133 n = 6	Part A SAD Cohort 3 AMG 133 n = 7	Part A SAD Cohort 4 AMG 133 n = 6	Part A SAD Cohort 5 AMG 133 n = 6	Part A SAD Cohort 6 AMG 133 n = 6	Part A SAD SC Placebo (Cohorts 1-5, 11) n = 12	Part A SAD IV Placebo (Cohort 6) n = 2	Part B MAD Cohort 7 AMG 133 n = 6	Part B MAD Cohort 8 AMG 133 n = 6	Part B MAD Cohort 9 AMG 133 n = 8	Part B MAD Cohort 10 AMG 133 n = 10	Part B MAD Cohorts 7-9 Placebo n = 6	Part B MAD Cohort 10 Placebo n = 3	Part A SAD Cohort 11 AMG 133 n = 6	Part C MAD Cohort 12 n = 6	Part C MAD Cohort 13 n = 8
Value	0	2	5	6	5	6	3	1	6	6	8	8	3	0	6	5	6

Population analysed: Full analysis set: all randomized participants who received at least one dose of AMG 133 or placebo.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality and serious adverse events, from enrollment to end of study; median duration (min, max) in months: 4.93 (0.13, 7.03). TEAEs from first dose of study drug until end of study; duration with median (min, max) in months: 4.93 (0.13, 7.03). TEAE time frame for Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A SAD Cohort 1 AMG 133	0 of 6 (0%)	0 of 6 (0%)	0 of 6
Part A SAD Cohort 2 AMG 133	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part A SAD Cohort 3 AMG 133	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7
Part A SAD Cohort 4 AMG 133	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part A SAD Cohort 5 AMG 133	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part A SAD Cohort 6 AMG 133	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part A SAD SC Placebo (Cohorts 1-5, 11)	0 of 12 (0%)	3 of 12 (25%)	0 of 12
Part A SAD IV Placebo (Cohort 6)	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part B MAD Cohort 7 AMG 133	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part B MAD Cohort 8 AMG 133	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part B MAD Cohort 9 AMG 133	0 of 8 (0%)	8 of 8 (100%)	0 of 8
Part B MAD Cohort 10 AMG 133	0 of 10 (0%)	8 of 10 (80%)	0 of 10
Part B MAD Cohorts 7-9 Placebo	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part B MAD Cohort 10 Placebo	0 of 3 (0%)	0 of 3 (0%)	0 of 3
Part A SAD Cohort 11 AMG 133	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part C MAD Cohort 12	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part C MAD Cohort 13	0 of 8 (0%)	6 of 8 (75%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 38316982Veniant 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Related trials for Obesity

RecruitingObservational study
Endoscopic Sleeve Gastroplasty (ESG) Prospective Trial for Obesity (EGO-Trial)
Obesity
Active, not recruitingPhase 4
Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing maridebart cafraglutide in people with Obesity, run by Amgen at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Part A: 150 days; Part B: 207 days; Part C Cohort 12: 193 days; Part C Cohort 13: 207 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04478708, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.