MET233 + MET097 for Obesity

Overseen By Metsera Recruiting

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Metsera

Must not be taking: Glucose-lowering medications

Disqualifiers: Pregnancy, Hypertension, Type 1 diabetes, others

Compensation: Varies

Number of Visits: 6

132 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have Type 2 diabetes and are in Part C, you must be on stable therapy for at least 30 days before joining.

What data supports the effectiveness of the drug MET233 + MET097 for obesity?

The research mentions that new drugs like GLP-1/GIP analogs, which are similar to MET233 + MET097, have shown promise in treating obesity. These drugs have been effective in managing weight and are paving the way for new treatments. ^{1 2 3 4 5}

How does the drug MET233 + MET097 for obesity differ from other treatments?

This treatment may be unique because it includes oral recombinant methionase (o-rMETase), which has been shown to prevent obesity in mice on a high-fat diet, potentially offering a novel approach compared to traditional dietary restrictions. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is designed to test how well the combination of MET233 with MET097 works to treat individuals with obesity or overweight with or without diabetes.

Eligibility Criteria

This trial is for adults with a BMI between 27 and 38, who may or may not have type 2 diabetes (T2DM). Those with T2DM must have stable treatment for at least a month. Excluded are individuals with high blood pressure, certain pancreatic conditions, uncontrolled heart rate, severe kidney issues, Type 1 diabetes, significant weight-related health problems, or recent weight loss treatments.

Inclusion Criteria

BMI ≥27 kg/m2 and ≤38.0 kg/m2 at screening

I have been diagnosed with type 2 diabetes for at least 3 months.

I don't have any significant health issues apart from my current condition.

Exclusion Criteria

Seated blood pressure higher than 160/100 mmHg at Screening visit or prior to the first study drug administration

I have never had pancreatitis or pancreatic cancer.

I have type 2 diabetes or my blood sugar levels are high.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Single Ascending Dose (SAD) Treatment

Participants receive a single subcutaneous dose of MET233 co-administered with MET097 or placebo

1 day

1 visit (in-person)

Multiple Ascending Dose (MAD) Treatment

Participants receive weekly subcutaneous doses of MET233 co-administered with MET097 or placebo

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks for Part A, 11 weeks for Parts B and C

Treatment Details

Interventions

• MET233 and MET097

Trial Overview The study tests the effectiveness of two drugs combined (MET233 and MET097) versus each drug alone and placebo in treating obesity. It aims to see if these drugs can help people lose weight and manage their diabetes better if they have it.

Participant Groups

Group I: SAD: MET233 co-administered with MET097 Experimental Treatment 1 Intervention

Participants in the single ascending dose cohorts will receive subcutaneous MET233 co-administered with MET097 at a single point in time.

Group II: MAD: MET233 co-administered with Placebo Experimental Treatment 1 Intervention

Participants will receive subcutaneous MET233 co-administered with Placebo weekly.

Group III: MAD: MET233 co-administered with MET097 Experimental Treatment 1 Intervention

Participants in the multiple ascending dose cohorts will receive subcutaneous MET233 co-administered with MET097 weekly.

Group IV: MAD: Placebo Placebo Group 1 Intervention

Participants in the multiple ascending dose cohorts will receive subcutaneous Placebo weekly.

Group V: SAD: Placebo Placebo Group 1 Intervention

Participants in the single ascending dose cohorts will receive subcutaneous Placebo at a single point in time.

Who Is Running the Clinical Trial?

Metsera

Lead Sponsor

Trials

3

Recruited

610+

Findings from Research

Liraglutide and semaglutide, GLP-1 receptor mimetics, have been approved for weight management in obese individuals, showing promising results in Phase III clinical trials.

Tirzepatide, a GLP-1R and GIPR co-agonist, has received Fast Track designation for obesity management and may offer fewer side effects, suggesting it could be a more sustainable option for long-term weight management compared to existing GLP-1R mimetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy. Lafferty, RA., Flatt, PR., Irwin, N.[2023]

A review of obesity drug therapies in development highlights various mechanisms, including central nervous system targets to reduce food intake and gastrointestinal lipase inhibitors to decrease fat absorption, indicating a multifaceted approach to treating obesity.

New drug combinations, such as topiramate with phentermine and bupropion with naltrexone, show promise for greater efficacy and fewer side effects, suggesting advancements in obesity treatment despite previous drug withdrawals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the pathophysiology and pharmacological treatment of obesity. Chugh, PK., Sharma, S.[2012]

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]

Mild to moderate obesity affects public health more significantly than severe obesity, indicating a need for effective management strategies targeting this larger population.

An individualized approach to obesity treatment, along with advancements in pharmacologic therapies, may offer better outcomes compared to traditional lifestyle and behavioral modifications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical therapy for obesity. Dayyeh, BK., Kaplan, LM.[2011]

Obesity is becoming a leading cause of premature death in developed countries, significantly impacting healthcare costs and quality of life, which highlights the urgent need for effective treatments.

Current pharmacotherapy options for obesity are limited, but the review discusses both existing anti-obesity medications and potential new agents that are in phase II and III clinical trials, emphasizing the importance of combining these treatments with lifestyle changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in development for the management of obesity. Vincent, RP., le Roux, CW.[2022]

In a study of 3,770 obese individuals from the Korean National Health and Nutrition Examination Survey, waist circumference and waist-to-height ratio were identified as the most accurate indicators of metabolically healthy obesity (MHO), outperforming traditional measures like body mass index.

The prevalence of MHO decreased with age, highlighting the importance of using waist measurements to better identify individuals who are obese but not at risk for metabolic syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of obesity indicators for metabolically healthy obesity: an observational study using the Korean National Health and Nutrition Examination Survey (2009-2010). Choi, MK., Han, YA., Roh, YK.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy. [2023]

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

Recent advances in the pathophysiology and pharmacological treatment of obesity. [2012]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Medical therapy for obesity. [2011]

5. India pubmed.ncbi.nlm.nih.gov

New agents in development for the management of obesity. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Oral Recombinant Methioninase Inhibits Diabetes Onset in Mice on a High-fat Diet. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Oral Recombinant Methioninase Prevents Nonalcoholic Fatty Liver Disease in Mice on a High Fat Diet. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Oral Recombinant Methioninase Prevents Obesity in Mice on a High-fat Diet. [2020]

9. China pubmed.ncbi.nlm.nih.gov

[METTL3 inhibitor STM2457 improves metabolic dysfunction-associated fatty liver disease by regulating mitochondrial function in mice]. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Utility of obesity indicators for metabolically healthy obesity: an observational study using the Korean National Health and Nutrition Examination Survey (2009-2010). [2022]