AMG 133 for Obesity With or Without Type 2 Diabetes

Not currently recruiting at 98 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must be taking: Metformin, Sulfonylureas, SGLT2 inhibitors

Disqualifiers: Pancreatitis, Thyroid carcinoma, Psychiatric disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMG 133, a potential drug, to evaluate its effectiveness in helping people lose weight and maintain it for a year. It targets two groups: individuals who are overweight or obese without diabetes and those with Type 2 diabetes. Participants will receive either the treatment or a placebo to compare outcomes. This trial may suit individuals who have struggled to lose weight and have conditions like high blood pressure or sleep apnea. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are in Cohort B with Type 2 diabetes, you must be on a stable treatment with metformin, a sulfonylurea, or an SGLT2 inhibitor for at least 90 days before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AMG 133 is generally safe. Most side effects, such as nausea and vomiting, were mild. Importantly, safety test results showed no major differences between those who took AMG 133 and those who did not. This suggests that AMG 133 is usually well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about AMG 133 for obesity, with or without type 2 diabetes, because it offers a novel approach compared to current treatments like lifestyle changes, Orlistat, or GLP-1 receptor agonists such as liraglutide. Unlike these existing options, AMG 133 targets the GLP-1/glucagon dual receptor, potentially enhancing its effectiveness in weight management. This dual-action mechanism could lead to more significant weight loss and better management of blood sugar levels, especially for those with type 2 diabetes. By offering a fresh mechanism of action, AMG 133 has the potential to provide a more effective solution for patients struggling with obesity.

What evidence suggests that this trial's treatments could be effective for obesity with or without Type 2 diabetes?

Research has shown that AMG 133, which participants in this trial may receive, yields promising results in weight loss. In studies, participants without Type 2 diabetes lost an average of up to 20% of their body weight. AMG 133 works by blocking one part of the body that affects appetite and metabolism while activating another part that helps control these functions. This combination has effectively reduced weight and improved health in both animal studies and early human trials. Initial findings suggest it could be a strong option for weight loss in people with obesity, regardless of Type 2 diabetes status. ^{1 3 4 5 6}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults over 18 with obesity or overweight, who've tried and failed to lose weight through diet. Cohort A includes those without diabetes; Cohort B includes those with Type 2 diabetes, managed by diet/exercise or certain medications. Excluded are individuals with weight changes >5kg in the last 3 months, specific psychiatric disorders, history of pancreatitis, or genetic conditions like MEN-2.

Inclusion Criteria

My BMI is over 30, or it's over 27 and I have a condition like high blood pressure or heart disease.

You have tried and failed to lose weight through dieting at least once.

I have type 2 diabetes with an HbA1c between 7% and 10%, and have been managing it for over 6 months.

Exclusion Criteria

I have a history of medullary thyroid cancer or MEN-2 in my family or myself.

You have gained or lost more than 5 kilograms (about 11 pounds) in the past 3 months.

I have had pancreatitis before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMG 133 or placebo in dose cohorts to assess dose response for weight loss

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they meet entry criteria

What Are the Treatments Tested in This Trial?

Interventions

• AMG 133
• Placebo

Trial Overview

The trial is testing three doses of AMG 133 against a placebo to see which dose is best at helping adults lose weight and maintain that loss over a year. It's divided into two groups: one for people just overweight/obese (Cohort A) and another for those also dealing with Type 2 diabetes (Cohort B).

How Is the Trial Designed?

Group I: Cohort B: Maridebart Cafraglutide Experimental Treatment 2 Interventions

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.

Group II: Cohort A: Maridebart Cafraglutide Experimental Treatment 2 Interventions

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.

Group III: Cohort A: Placebo Placebo Group 2 Interventions

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.

Group IV: Cohort B: Placebo Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight loss in overweight or obese patients with type 2 diabetes, showing significant reductions in weight compared to placebo across multiple studies involving 27 trials.

There was no significant difference in weight loss efficacy among the different GLP-1 RAs tested, indicating that they are similarly effective options for managing weight in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis. Potts, JE., Gray, LJ., Brady, EM., et al.[2022]

Weight loss is crucial in preventing and managing Type 2 diabetes, and pharmacological treatments should not only promote weight loss but also improve insulin sensitivity.

Metformin is highlighted as the first-line medication for obese diabetic patients because it effectively reduces insulin resistance and improves blood sugar control without causing weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of the obese diabetic patient. Scheen, AJ., Lefebvre, PJ.[2018]

In a phase 2 study involving 474 participants with class II/III obesity, JNJ-64565111, a dual agonist, led to significant weight loss compared to placebo, with reductions of up to 10.0% in body weight at week 26.

While JNJ-64565111 was effective in reducing weight in a dose-dependent manner, it also resulted in a higher incidence of treatment-emergent adverse events, particularly nausea and vomiting, compared to both placebo and liraglutide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of glucagon-like peptide-1/glucagon receptor co-agonist JNJ-64565111 in individuals with obesity without type 2 diabetes mellitus: A randomized dose-ranging study. Alba, M., Yee, J., Frustaci, ME., et al.[2022]

Pharmacologic treatments for obesity, such as phentermine, sibutramine, and orlistat, typically lead to an additional weight loss of about 2-5 kg compared to placebo, but there is a need for more effective and safer options.

Several new antiobesity drugs are in late-stage development, targeting various mechanisms like appetite suppression and nutrient absorption, which may enhance treatment options for obesity in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugs in the pipeline for the obesity market. Klonoff, DC., Greenway, F.[2021]

The combination of phentermine and topiramate is currently the most effective FDA-approved treatment for obesity, followed by lorcaserin and bupropion/naltrexone.

Effective obesity management should consider not only medication efficacy but also comorbidities, drug interactions, and personalized treatment approaches based on individual genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Obesity Treatments Including Pharmacogenetic and Nutrigenetic Approaches. Solas, M., Milagro, FI., Martínez-Urbistondo, D., et al.[2018]

Citations

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RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY ...

In the Phase 2 study, MariTide demonstrated up to ~20% average weight loss in people living with obesity without Type 2 diabetes (T2D) compared ...

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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 ...

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pmc.ncbi.nlm.nih.gov/articles/PMC10896721/

A GIPR antagonist conjugated to GLP-1 analogues promotes ...

Here, we confirm the GIPR antagonist and GLP-1R agonist activities in cell-based systems and report the ability of AMG 133 to reduce body weight and improve ...

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nature.com/articles/s41574-024-00967-z

Phase I results for AMG 133 | Nature Reviews Endocrinology

Treating male obese mice and cynomolgus monkeys with AMG 133 resulted in reduced body weight and improved metabolic parameters, including blood ...

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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 ...

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RESULTS FROM AMGEN'S PHASE 2 OBESITY STUDY ...

In the Phase 2 study, MariTide demonstrated up to ~20% average weight loss in people living with obesity without Type 2 diabetes (T2D) compared ...