NNC0662-0419 for Obesity

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Disqualifiers: Diabetes, Pancreatitis, Thyroid disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug NNC0662-0419 for obesity?

Research shows that losing even 5% of body weight can lead to significant health improvements for people with obesity. This level of weight loss is often used as a benchmark for the effectiveness of new obesity drugs. ^{1 2 3 4 5}

What makes the drug NNC0662-0419 unique for treating obesity?

The drug NNC0662-0419 may be unique due to its potential involvement with nesfatin-1, a molecule that reduces food intake and is linked to energy balance and metabolic functions, which could offer a novel approach compared to existing obesity treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is testing a new study medicine which may be used to treat people living with overweight or obesity. The purpose of the study is to see if the new study medicine is safe, how it works in human body and what human body does to the study medicine. Participants will either get the study medicine NNC0662-0419 or placebo (a "dummy" medicine without any active ingredients) given by study staff as an injection under participants skin. Which treatment participants will get is decided by chance. NNC0662-0419 is a new medicine, which cannot be prescribed by doctors. This is the first time the medicine is being given to humans. The study will last for about 9 months.

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This trial is for individuals living with overweight or obesity. Participants will be randomly assigned to receive either the new study medicine NNC0662-0419 or a placebo, which has no active ingredients. The treatment involves injections under the skin and the study spans approximately 9 months.

Inclusion Criteria

I am either male or female by birth.

I am between 19 and 55 years old.

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

Exclusion Criteria

Glycated haemoglobin (HbA1c) >= 6.5% (48 mmol/mol) at screening

Amylase >= 2 times upper limit of normal at screening

Lipase >= times upper limit of normal at screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive a single dose of NNC0662-0419 or placebo at one of five dose levels

6 weeks

Multiple Ascending Dose (MAD)

Participants receive NNC0662-0419 or placebo once-weekly for 4 weeks at one of four dose levels

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NNC0662-0419

Trial Overview The trial is evaluating the safety and biological effects of NNC0662-0419, a new medication that cannot yet be prescribed by doctors. This first-in-human study aims to understand how this potential obesity treatment works in the body and what the body does to it.

Participant Groups

Group I: Part B: Multiple ascending dose (MAD) Experimental Treatment 2 Interventions

Participants will receive NNC0662-0419 once-weekly for 4 weeks at any of the four different dose levels or matching placebo in a sequential manner with the dose increasing between cohorts.

Group II: Part A: Single ascending dose (SAD) Experimental Treatment 2 Interventions

Participants will receive a single dose of any of the five different dose levels of NNC0662-0419 or matching placebo in a sequential manner with the dose increasing between cohorts.

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

A modest weight loss of over 5% can lead to significant health improvements for individuals with obesity, while losses of 10%-15% provide even greater benefits, regardless of the final BMI.

The Brazilian Society of Endocrinology and Metabolism and the Brazilian Society for the Study of Obesity propose a new classification system based on maximum weight attained in life (MWAL), encouraging a focus on maintaining weight loss rather than solely aiming for a normalized BMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO). Halpern, B., Mancini, MC., de Melo, ME., et al.[2023]

Losing just 5% of body weight can lead to significant health improvements, but many individuals struggle to maintain weight loss through diet and exercise alone, highlighting the need for additional treatment options.

As of 2012, two new medications, lorcaserin and phentermine/topiramate, have been approved for long-term obesity treatment, and bariatric surgery is recommended for patients with severe obesity (BMI ≥40 or ≥35 with comorbidities) as a more intensive intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. Kushner, RF., Apovian, CM., Fujioka, K.[2018]

Obesity in older adults is linked to several health risks, including cardiovascular issues and impaired mobility, but it may also provide some protection against hip fractures; however, the relationship between obesity and mortality decreases with age.

Intensive counseling that includes behavioral, dietary, and exercise strategies can lead to modest weight loss (3 to 4 kg) over 1 to 3.3 years, which is associated with improved health outcomes like better glucose tolerance and reduced risk of diabetes and cardiovascular problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity in older adults: a systematic review of the evidence for diagnosis and treatment. McTigue, KM., Hess, R., Ziouras, J.[2021]

Weight loss of at least 5% can lead to significant improvements in health outcomes for individuals with obesity, including reductions in cardiometabolic risk factors, and is a key target for the approval of new anti-obesity medications.

For certain obesity-related conditions, such as type 2 diabetes and non-alcoholic steatohepatitis, greater weight loss (≥10% or ≥15%) may be necessary to achieve meaningful health improvements, highlighting the need for personalized weight loss goals based on individual health profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review. Horn, DB., Almandoz, JP., Look, M.[2022]

Long-term maintenance of weight loss in patients with obesity, particularly those with non-insulin dependent diabetes mellitus (NIDDM), remains a significant challenge despite initial weight reductions.

Implementing a continuous care model that includes ongoing professional support, skills training, social support, and exercise can significantly improve the chances of maintaining weight loss over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for improving maintenance of weight loss. Toward a continuous care model of obesity management. Perri, MG., Sears, SF., Clark, JE.[2022]

The study found that higher body mass index (BMI) is associated with a lower ratio of nesfatin-1/NUCB-2 in cerebrospinal fluid compared to plasma, suggesting that obesity may reduce the brain's uptake of this appetite-regulating hormone.

Nesfatin-1/NUCB-2 levels in the brain are positively correlated with plasma levels, indicating that understanding this relationship could help in developing treatments for obesity, as nesfatin-1/NUCB-2 has potential weight-reducing effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased cerebrospinal fluid/plasma ratio of the novel satiety molecule, nesfatin-1/NUCB-2, in obese humans: evidence of nesfatin-1/NUCB-2 resistance and implications for obesity treatment. Tan, BK., Hallschmid, M., Kern, W., et al.[2019]

In a 16-week study involving 140 overweight adults, the herbal extract LI85008F led to significant weight loss (5.36 kg) and reductions in BMI compared to a placebo group, indicating its efficacy for weight management.

Participants taking LI85008F also experienced improvements in their lipid profiles, with decreased LDL cholesterol and increased HDL cholesterol, and no major adverse events were reported, highlighting its safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a novel herbal formulation for weight loss demonstrated in a 16-week randomized, double-blind, placebo-controlled clinical trial with healthy overweight adults. Dixit, K., Kamath, DV., Alluri, KV., et al.[2019]

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]

The Intensive Lifestyle Intervention (ILI) led to a significant weight loss of 7.19 kg at 12 months compared to usual care (UC) in a study involving 803 underserved patients with obesity, indicating its efficacy in promoting weight loss.

Several factors, including improvements in eating behaviors and physical activity, partially explained the weight loss during the ILI, but the ILI group experienced some weight regain by month 24, suggesting the need for ongoing support to maintain weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mediators of weight change in underserved patients with obesity: exploratory analyses from the Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL) cluster-randomized trial. Dorling, JL., Martin, CK., Yu, Q., et al.[2023]

A high-intensity lifestyle intervention for obesity, delivered in primary care clinics serving low-income populations, resulted in a significant weight loss of -4.99% over 24 months, compared to only -0.48% in the usual care group, indicating its effectiveness.

The study involved 803 adults, with 83.4% completing the trial, and found no significant differences in serious adverse events between the intensive intervention and usual care, suggesting the program is safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight Loss in Underserved Patients - A Cluster-Randomized Trial. Katzmarzyk, PT., Martin, CK., Newton, RL., et al.[2021]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Proposal of an obesity classification based on weight history: an official document by the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society for the Study of Obesity and Metabolic Syndrome (ABESO). [2023]

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

Obesity consults--comprehensive obesity management in 2013: understanding the shifting paradigm. [2018]

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

Obesity in older adults: a systematic review of the evidence for diagnosis and treatment. [2021]

4. England pubmed.ncbi.nlm.nih.gov

What is clinically relevant weight loss for your patients and how can it be achieved? A narrative review. [2022]

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

Strategies for improving maintenance of weight loss. Toward a continuous care model of obesity management. [2022]

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

Decreased cerebrospinal fluid/plasma ratio of the novel satiety molecule, nesfatin-1/NUCB-2, in obese humans: evidence of nesfatin-1/NUCB-2 resistance and implications for obesity treatment. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of a novel herbal formulation for weight loss demonstrated in a 16-week randomized, double-blind, placebo-controlled clinical trial with healthy overweight adults. [2019]

8. 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]

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

Mediators of weight change in underserved patients with obesity: exploratory analyses from the Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL) cluster-randomized trial. [2023]

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

Weight Loss in Underserved Patients - A Cluster-Randomized Trial. [2021]