NNC0487-0111 for Obesity

Recruiting at 2 trial locations

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes, Vitamin D deficiency, others

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

Compensation: Varies

Number of Visits: Unknown

125 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called NNC0487-0111, given as an injection under the skin, to see if it is safe and how it works in the body.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinator or your doctor for guidance.

What evidence supports the effectiveness of the drug NNC0487-0111 for obesity?

Cagrilintide, an amylin analog similar to components in NNC0487-0111, has shown promising weight loss results in combination with semaglutide, a GLP-1 receptor agonist, by reducing appetite and increasing insulin production. This combination therapy approach targets multiple pathways in the body, which may enhance weight loss effectiveness. ^{1 2 3 4 5}

What makes the drug NNC0487-0111 unique for treating obesity?

NNC0487-0111, also known as Amycretin, is unique because it may involve components like nesfatin-1, a peptide that helps regulate appetite and energy balance, which could offer a novel approach to managing obesity compared to existing treatments. ^{6 7 8 9 10}

Research Team

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for men and women aged 18-55 with a BMI between 27.0 and 39.9, indicating overweight due to excess fat as assessed by the study's doctor. Participants must pass health checks including vital signs, heart tests, and lab tests. Those with conditions affecting safety or protocol adherence, high blood sugar levels (HbA1c ≥6.5%), very low vitamin D, abnormal parathyroid hormone or calcium levels, or significantly elevated amylase/lipase/calcitonin are excluded.

Inclusion Criteria

I am either male or female.

Body Mass Index (BMI) between 27.0 and 39.9 kg/m^2 (both inclusive) at screening. Overweight should be due to excess adipose tissue, as judged by the investigator

Considered eligible based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator

Exclusion Criteria

Calcitonin equal to or greater than 50 ng/L at screening

Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol

HbA1c equal to or greater than 6.5 % (48 mmol/mol) at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single ascending dose (SAD) of NNC0487-0111 or placebo

25 days

Multiple visits

Treatment Parts B to E

Participants receive multiple ascending doses (MAD) of NNC0487-0111 or placebo

255 days

Multiple visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 days

Treatment Details

Interventions

• NNC0487-0111

Trial Overview The trial is testing NNC0487-0111, a new drug given as an under-the-skin injection to see if it's safe and how it works in people with obesity compared to a placebo (a substance with no active drug).

Participant Groups

Group I: NNC0487-0111 Experimental Treatment 2 Interventions

Participants will be randomized to receive NNC0487-0111. The study will be conducted in 5 parts. Part A: Single ascending dose (SAD) Part B, C, D and E: Multiple ascending dose (MAD)

Group II: Placebo Placebo Group 2 Interventions

Participants will be randomized to receive Placebo. The study will be conducted in 5 parts. Part A: Single ascending dose (SAD). Part B,C,D and E: Multiple ascending dose (MAD).

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

Cagrilintide, an amylin-analog, is being developed alongside semaglutide, a GLP-1 receptor agonist, to enhance weight loss in individuals with obesity, leveraging their complementary mechanisms to reduce appetite.

Clinical trials have shown that both cagrilintide alone and in combination with semaglutide lead to promising weight loss results, supporting the potential of this combination therapy for effective long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. D'Ascanio, AM., Mullally, JA., Frishman, WH.[2023]

In a study of 258 individuals with obesity or overweight in Switzerland, 71.3% of those receiving reimbursed liraglutide 3.0 mg achieved significant weight loss targets at Week 16, indicating its efficacy in real-world settings.

By Month 10, participants who met the initial weight loss criteria experienced an average total weight loss of 12.4% from baseline, demonstrating that liraglutide can lead to clinically meaningful weight reduction over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss and treatment patterns in a real-world population of adults receiving liraglutide 3.0 mg for weight management in routine clinical practice in Switzerland (ADDRESS study). Schultes, B., Timper, K., Cavadini, G., et al.[2023]

Obesity is a major health issue in Western countries, causing approximately 300,000 deaths annually in the U.S. and increasing the risk for various diseases, including liver disease and colon cancer.

Effective management of obesity includes lifestyle changes, and in some cases, medications or surgery, with a target of losing 10% of body weight within 6 months; currently, only two medications, sibutramine and orlistat, are approved for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of obesity. Kushner, RF.[2005]

Retatrutide, a triple agonist targeting incretin receptors, has shown significant weight loss and reductions in glycated hemoglobin (HbA1c) in phase-2 trials for individuals with type 2 diabetes mellitus (T2DM), as well as substantial weight loss in non-T2DM individuals, although gastrointestinal side effects were noted.

Concerns about cardiovascular safety have emerged due to dose-dependent increases in heart rate and mild to moderate cardiac arrhythmias, highlighting the need for long-term cardiovascular outcome trials to assess its safety in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retatrutide: a triple incretin receptor agonist for obesity management. Ray, A.[2023]

In a study of 60 severely obese patients who underwent biliopancreatic diversion with duodenal switch (BPD/DS), nesfatin-1 levels decreased significantly over 12 months post-surgery, indicating a potential role in weight loss and metabolic regulation.

At 12 months, lower nesfatin-1 levels were positively correlated with improved metabolic health markers, such as reduced insulin resistance and lower cholesterol levels, suggesting that nesfatin-1 may be linked to better metabolic outcomes in severely obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between nesfatin-1 levels and metabolic improvements in severely obese patients who underwent biliopancreatic derivation with duodenal switch. St-Pierre, DH., Martin, J., Shimizu, H., et al.[2019]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Cetilistat for the treatment of obesity. [2017]

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

Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. [2023]

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

Weight loss and treatment patterns in a real-world population of adults receiving liraglutide 3.0 mg for weight management in routine clinical practice in Switzerland (ADDRESS study). [2023]

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

Medical management of obesity. [2005]

5. England pubmed.ncbi.nlm.nih.gov

Retatrutide: a triple incretin receptor agonist for obesity management. [2023]

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

Does adiponectin upregulation attenuate the severity of acute pancreatitis in obesity? [2021]

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

Association between nesfatin-1 levels and metabolic improvements in severely obese patients who underwent biliopancreatic derivation with duodenal switch. [2019]

8. Romania pubmed.ncbi.nlm.nih.gov

SERUM NESFATIN-1 LEVEL IN HEALTHY SUBJECTS WITH WEIGHT-RELATED ABNORMALITIES AND NEWLY DIAGNOSED PATIENTS WITH TYPE 2 DIABETES MELLITUS; A CASE-CONTROL STUDY. [2022]

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

Adiponectin receptor-1 expression is decreased in the pancreas of obese mice. [2009]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance. [2022]