NNC0487-0111 for Obesity

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new injection treatment, NNC0487-0111, to evaluate its safety and effectiveness in individuals with obesity. Participants will receive either the actual treatment or a placebo (a harmless, inactive substance) for comparison. Ideal candidates are adults with a Body Mass Index (BMI) between 27 and 39.9, indicating overweight due to excess body fat. The study is divided into parts with gradually increasing doses to assess safety and effectiveness. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in obesity treatment.

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.

Is there any evidence suggesting that NNC0487-0111 is likely to be safe for humans?

Research has shown that NNC0487-0111, a treatment for obesity, has a good safety record. In earlier studies with individuals who are overweight or have obesity, this medication was generally well-tolerated. The results indicated that its safety is comparable to other treatments in its category, which are known to be quite safe.

Participants in these studies did not report any unexpected or severe side effects. The treatment, administered as an injection under the skin, worked well without causing major issues. While some mild side effects were noted, they resembled those seen with similar medications.

In summary, current data suggest that NNC0487-0111 is safe for humans based on previous research. However, ongoing studies will continue to monitor its safety closely. ^{1 2 3 4 5}

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

Unlike the standard treatments for obesity, which often focus on appetite suppression or fat absorption, NNC0487-0111 is unique because it potentially targets metabolic pathways to enhance energy expenditure. Researchers are excited about this treatment because it introduces a novel mechanism of action that could offer more sustainable weight loss by altering the body's energy balance. Additionally, the approach of using both single and multiple ascending doses might optimize its effectiveness and safety compared to existing therapies.

What evidence suggests that NNC0487-0111 might be an effective treatment for obesity?

Research has shown that the drug NNC0487-0111, also known as amycretin, may aid in weight loss. In one study, participants taking 100 mg of amycretin daily lost an average of 13.1% of their body weight, while those on a placebo lost only 1.2%. Participants in this trial will receive either NNC0487-0111 or a placebo at random. This medication mimics two natural hormones in the body, amylin and GLP-1, which help regulate appetite and food intake. Early trials suggested that amycretin is effective and safe, with most side effects being mild. No other oral drug has matched amycretin's effectiveness for weight loss. ^{2 3 6 7 8}

Who Is on the Research Team?

Clinical Transparency dept. 2834

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01185-7/abstract

results from a phase 1b/2a randomised controlled study The aim of this study was to investigate the safety, tolerability, pharmacokinetics, and effects on bodyweight of subcutaneous amycretin ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05369390

A Research Study on How NNC0487-0111 Works in ... NNC0487-0111 is a new medicine similar to 2 hormones that are produced in human body: amylin and glucagon-like peptide-1 (GLP-1).

3. prnewswire.com prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html

Novo Nordisk advances early-stage obesity medication ... Exploratory results showed participants taking 100 mg per day of oral amycretin achieved a mean weight loss of 13.1% versus 1.2% with placebo ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625011857

Amycretin, a novel, unimolecular GLP-1 and amylin ... Recent phase 1 clinical trial data have reported that oral amycretin appeared safe and tolerable (most treatment-emergent adverse events were ...

5. acc.org acc.org/Latest-in-Cardiology/Journal-Scans/2025/07/02/14/43/Oral-Subcutaneous-Amycretin

Oral, Subcutaneous Amycretin Similarly Safe, Tolerated as ... 1% in placebo. "To date, no other oral drug has shown the same level of effectiveness in reducing body weight as observed with amycretin in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40550231/

Amycretin, a novel, unimolecular GLP-1 and amylin ... In people with overweight or obesity, once-weekly subcutaneous amycretin up to 60 mg had a safety and tolerability profile consistent with GLP-1 and amylin ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40550229/

a first-in-human, phase 1, double-blind, randomised ... Interpretation: In people with overweight or obesity, amycretin appeared safe and tolerable. Results from this first-in-human, phase 1 study ...

8. novonordisk-trials.com novonordisk-trials.com/trials-conditions/all-trials-v2/NN9490-8213.html

A Research Study on How NNC0487-0111, a New ... The study is testing a new medicine (NNC0487-0111) for weight control in Chinese people with BMI between 24 kilogram per meter square (kg/m2) and 34.9 kg/m2 ...