AMG 133 for Obesity With or Without Type 2 Diabetes

Recruiting at 81 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

592 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug AMG 133 for obesity with or without type 2 diabetes?

The research mentions that drugs like glucagon-like peptide-1 receptor agonists, which are used for diabetes, can also help with weight loss in overweight or obese patients. This suggests that drugs targeting similar pathways might be effective for obesity. ^{1 2 3 4 5}

How does the drug AMG 133 for obesity differ from other treatments?

AMG 133 is unique because it is a new drug being tested specifically for obesity, with or without type 2 diabetes, and it may work differently from existing treatments by targeting different mechanisms in the body. Unlike some current drugs that focus on appetite suppression or nutrient absorption, AMG 133 could offer a novel approach, although its exact mechanism is still under investigation. ^{2 6 7 8 9}

What is the purpose of this trial?

This trial is testing AMG 133, a new drug, to see if it helps people lose weight and keep it off. It targets overweight or obese individuals, both with and without Type 2 diabetes. The drug may work by affecting metabolism or appetite.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

Group I: Cohort B: AMG 133 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 AMG 133 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 AMG 133 or Placebo in 1 of 4 dose cohorts.

Group II: Cohort A: AMG 133 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 AMG 133 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 AMG 133 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 AMG 133 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 AMG 133 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 AMG 133 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 AMG 133 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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Precision Obesity Treatments Including Pharmacogenetic and Nutrigenetic Approaches. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for obesity. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Benefits and Harms in Pivotal Trials of Oral Centrally Acting Antiobesity Medicines: A Systematic Review and Meta-Analysis. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of obesity - state of the art. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Drugs in the pipeline for the obesity market. [2021]

8. France pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of the obese diabetic patient. [2018]

9. England 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. [2022]