Cagrilintide + Semaglutide for Obesity

No longer recruiting at 2 trial locations

Overseen By Novo Nordisk

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Disqualifiers: Pregnancy, Amylin analogue, others

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

Compensation: Varies

Number of Visits: 28

Duration: 22 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two medicines, cagrilintide (an experimental treatment) and semaglutide, to determine if administering them together in one injection differs from separate injections for weight management in individuals with overweight or obesity. Researchers aim to understand how these methods affect the medicines' levels in the blood. Participants will begin with separate injections and may switch to a combined injection. Individuals with a BMI (body mass index) between 27.0 and 39.9 due to excess body fat might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new 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. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using cagrilintide and semaglutide together is generally safe for people. Studies have found that adults who are overweight or obese can lose a significant amount of weight without major safety issues. The most common side effects involve the stomach, such as nausea or vomiting. These effects are typical for drugs like semaglutide, which is already approved for other uses. The combination is well-tolerated and has a safety profile similar to other drugs in this category. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, cagrilintide and semaglutide, because they combine two promising drugs to tackle obesity in a novel way. Unlike standard options like diet, exercise, or medications like orlistat, these drugs target hunger and satiety signals in the brain more effectively. Cagrilintide is a new active ingredient that mimics a hormone helping regulate appetite, while semaglutide, already used for diabetes, enhances insulin secretion and reduces hunger. Additionally, combining them into a single injection could make the treatment more convenient and potentially more effective, offering a fresh approach to weight management.

What evidence suggests that this trial's treatments could be effective for overweight and obesity?

This trial will evaluate the combination of cagrilintide and semaglutide for weight loss. Research has shown that using these two medications together aids in weight loss. In one study, this combination resulted in more weight loss than a placebo (a treatment with no active ingredients). Another study found that these medications together caused significant weight loss in adults. Semaglutide alone has also been shown to aid in weight loss. These medicines complement each other by affecting different parts of the body that control hunger and weight. Using them together may enhance these effects, offering a promising approach to managing overweight or obesity. ^{4 6 7 8 9}

Who Is on the Research Team?

Clinical Transparency (dept. 1452)

Principal Investigator

Novo Nordisk A/S

Are You a Good Fit for This Trial?

Inclusion Criteria

Male or female of non-childbearing potential (NCBP)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cagrilintide and semaglutide as separate injections for 14 weeks, followed by either combined or separate injections for 8 weeks

22 weeks

28 visits (in-person), 4 extended stays

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 days

What Are the Treatments Tested in This Trial?

Interventions

• Cagrilintide
• Semaglutide

How Is the Trial Designed?

Group I: Part B: Cagrilintide and semaglutide combined in DV3384 device Experimental Treatment 1 Intervention

Participants will receive a single injection of Cagrilintide 0.25 mg/semaglutide 0.25 mg using the DV3384 manual syringe followed by a 28 days follow-up period.

Group II: Part A: Cagrilintide and semaglutide in separate syringes Experimental Treatment 2 Interventions

Participants will up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks treatment with cagrilintide and semaglutide administered as separate injections. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination). Followed by a 38 days follow-up period.

Group III: Part A: Cagrilintide and semaglutide combined in DV3384 device Experimental Treatment 1 Intervention

Participants will be up-titrated for 14 weeks (dose escalation every 4 weeks and 2 weeks at last dose escalation step prior to randomisation) with cagrilintide and semaglutide administered as separate injections. Followed by 8 weeks of treatment with cagrilintide and semaglutide administered using the DV3384 manual syringe. The 8-week treatment period covers 2 different doses of cagrilintide and semaglutide (1.7/1.7 mg and 2.4/2.4 mg with 4 weeks on each dose combination. Followed by a 38 days follow-up period.

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

In a phase 3 trial involving 388 treatment-naive patients with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.45% with 0.5 mg and 1.55% with 1.0 mg doses compared to placebo, indicating its efficacy in improving glycaemic control.

Semaglutide also led to significant weight loss, with reductions of 3.73 kg and 4.53 kg for the respective doses, while maintaining a safety profile similar to existing GLP-1 receptor agonists, with most adverse events being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Sorli, C., Harashima, SI., Tsoukas, GM., et al.[2022]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

In a 32-week trial with 92 participants, the combination of semaglutide and cagrilintide (CagriSema) led to a significant reduction in HbA1c levels compared to cagrilintide alone, indicating improved glycemic control in individuals with type 2 diabetes.

CagriSema also resulted in greater weight loss compared to both semaglutide and cagrilintide, demonstrating its potential as an effective treatment option for managing weight and blood sugar levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Frias, JP., Deenadayalan, S., Erichsen, L., et al.[2023]

In a 52-week study involving 731 patients with type 2 diabetes, oral semaglutide significantly reduced HbA1c levels and body weight compared to placebo, demonstrating its efficacy when added to insulin with or without metformin.

The most common side effect of oral semaglutide was nausea, which was mostly mild to moderate, indicating a safety profile similar to other glucagon-like peptide 1 receptor agonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Zinman, B., Aroda, VR., Buse, JB., et al.[2022]

Oral semaglutide, a GLP-1 analogue, was found to be safe and well-tolerated in two clinical trials involving 135 healthy males and 23 males with type 2 diabetes, with most adverse events being mild and primarily gastrointestinal.

The pharmacokinetics showed that semaglutide exposure increased with higher doses and was consistent across healthy individuals and those with type 2 diabetes, supporting its suitability for once-daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. Granhall, C., Donsmark, M., Blicher, TM., et al.[2020]

In the SUSTAIN 1 to 5 trials involving 3918 participants with type 2 diabetes, semaglutide significantly helped more individuals achieve their HbA1c targets (47% to 74%) compared to placebo (7% to 19%) and other active comparators (16% to 29%).

Semaglutide was effective in achieving these results while minimizing unwanted outcomes, such as weight gain, severe hypoglycaemia, and gastrointestinal side effects, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. DeVries, JH., Desouza, C., Bellary, S., et al.[2022]

Citations

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NCT04940078 | A Research Study to Compare Blood ...

This study will compare two different ways of giving cagrilintide and semaglutide for treating overweight and obesity.

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Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 ...

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This study will compare the blood levels of cagrilintide and semaglutide when the same dose is given in two different versions of CagriSema. CagriSema is a ...

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Trial product estimand is the difference in mean change in body weight from baseline to week 68 for all randomised participants, had all ...

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A Research Study to Compare Blood Levels of Cagrilintide ...

Research shows that combining semaglutide with cagrilintide (CagriSema) can help with weight loss in people with type 2 diabetes. Semaglutide alone has been ...

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nejm.org/doi/full/10.1056/NEJMoa2502081

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Cagrilintide–semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo.

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Efficacy and Safety of Cagrilintide Alone and in ...

Cagrisema outperforms semaglutide regarding weight loss. Cagrilintide shows comparable weight loss to semaglutide/liraglutide with significantly lower vomiting.

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clinicaltrials.gov

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NCT05394519 | A Research Study to See How Well ...

This study will look at how well the new medicine CagriSema helps people living with excess body weight and type 2 diabetes losing weight.

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The next frontier in metabolic health: Cagrilintide-Semaglutide ...

The safety profile of CagriSema is generally consistent with that of GLP-1RA class drugs. The most common adverse events were gastrointestinal (GI) symptoms, ...