BI 456906 for Obesity

(SYNCHRONIZE™-1 Trial)

Not currently recruiting at 146 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: Obesity medications, Glucose-lowering agents

Disqualifiers: Type 2 diabetes, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 17

Duration: 76 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a medicine called survodutide (also known as BI 456906) can help people with obesity lose weight. Participants will be randomly assigned to one of three groups: two groups will receive different doses of survodutide, and one group will receive a placebo (a substance with no active drug). The study is open to adults with a BMI of 30 or higher, or a BMI of 27 or higher with a related health issue like high blood pressure or sleep apnea, who have struggled to lose weight through diet changes alone. People with type 2 diabetes cannot join the trial. Participants will take weekly injections and receive diet and exercise guidance over about 19 months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment for obesity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking medication for obesity, you must stop at least 3 months before joining the study.

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

Research has shown that survodutide, the treatment under study for obesity, has promising safety results from earlier studies. In these tests, survodutide helped individuals with overweight or obesity achieve significant weight loss, with reports of nearly 19% weight reduction. Importantly, these studies also assessed the treatment's safety and tolerability, examining how well participants managed it.

The evidence suggests that survodutide is generally well-tolerated, with most participants not experiencing serious side effects. However, like any medication, some individuals might still encounter mild to moderate side effects. Prospective clinical trial participants should discuss any safety concerns or questions with the study team. ^{1 2 3 4 5}

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

Researchers are excited about Survodutide because it offers a new approach to treating obesity by targeting the GLP-1 receptor, which plays a crucial role in appetite regulation and body weight management. Unlike standard treatments that primarily focus on lifestyle changes or medications like orlistat and phentermine-topiramate, Survodutide is a peptide-based medication that may provide more effective weight loss by enhancing satiety and reducing food intake. Additionally, with dosing options at 3.6 mg and 6.0 mg, Survodutide offers flexibility in treatment, allowing for personalized dosages that could optimize results for different patients. This innovative mechanism and tailored approach could significantly improve outcomes for individuals struggling with obesity.

What evidence suggests that this treatment might be an effective treatment for obesity?

Research has shown that survodutide (BI 456906) can help people with obesity lose a significant amount of weight. One study found that participants lost almost 19% of their body weight after taking survodutide. This trial will test different dosages, specifically 3.6 mg and 6.0 mg, to evaluate its effectiveness in weight management and improving heart health in people with obesity. These findings suggest it could be a promising option for those who haven't succeeded with other weight loss methods. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 without diabetes, with a BMI of at least 30 kg/m² or a BMI of 27 kg/m² plus weight-related health issues. Candidates should have tried and failed to lose weight through dieting before.

Inclusion Criteria

I have obstructive sleep apnea.

My condition meets other specific criteria not listed.

I have high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive survodutide or placebo injections weekly and counseling for diet and exercise

76 weeks

14 visits (in-person), 6 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• BI 456906

Trial Overview The study tests survodutide (BI 456906) on people with obesity, comparing two different doses against a placebo. Participants will self-inject weekly for around one and a half years while also receiving lifestyle counseling.

How Is the Trial Designed?

Group I: Survodutide 6.0 mg Experimental Treatment 1 Intervention

Group II: Survodutide 3.6 mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

In two phase I studies involving a total of 149 participants, the dual agonist BI 456906 demonstrated significant weight loss, with a maximum placebo-corrected reduction of 13.8% in body weight observed at week 16 in the multiple rising dose study.

While BI 456906 showed promising efficacy in promoting weight loss, it was associated with an increase in drug-related adverse events, particularly gastrointestinal issues and decreased appetite, leading to discontinuation in some participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Jungnik, A., Arrubla Martinez, J., Plum-Mörschel, L., et al.[2023]

GLP-1 receptor agonists, specifically semaglutide, have been shown to significantly promote weight loss in clinical trials, with superior efficacy compared to placebo and other antidiabetic medications.

The STEP trial demonstrated that a higher dose of semaglutide (2.4 mg, once-weekly) specifically targets obesity, leading to its FDA approval as Wegovy for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wegovy (semaglutide): a new weight loss drug for chronic weight management. Singh, G., Krauthamer, M., Bjalme-Evans, M.[2022]

Tirzepatide, administered once weekly, was found to be effective in reducing obesity in individuals with type 2 diabetes, as demonstrated in a large phase 3 trial involving multiple centers.

The study was double-blind and placebo-controlled, ensuring robust results that support tirzepatide as a promising treatment option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. Davidson, MB.[2023]

In the SURMOUNT-1 trial, tirzepatide significantly reduced the 10-year predicted risk of developing type 2 diabetes (T2D) compared to placebo, with reductions ranging from 12.4% to 14.7% at week 72, depending on the dosage.

Participants with prediabetes experienced greater risk score reductions (16.0%-20.3%) than those without prediabetes (10.1%-11.3%), indicating that tirzepatide is effective across different glycaemic statuses and body mass index levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial. Hankosky, ER., Wang, H., Neff, LM., et al.[2023]

Lifestyle changes like diet, exercise, and behavioral therapy are essential for treating obesity, and if these do not lead to a 5% weight loss in 3 to 6 months, medications may be considered for patients with a BMI of 30 or higher, or 27 with related health issues.

Current obesity medications like orlistat, sibutramine, and rimonabant can lead to moderate weight loss and improved cardiovascular health, particularly enhancing glucose metabolism, but their side effects must be carefully evaluated before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. Hamann, A.[2021]

Several anti-obesity drugs have been withdrawn from the market due to serious cardiovascular risks, such as fenfluramine and sibutramine, highlighting the importance of safety in obesity treatments.

Current treatments like GLP-1 analogues and metformin not only aid in weight loss but also have favorable cardiovascular profiles, suggesting they could be effective options for managing obesity alongside type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of current and future anti-obesity drugs. Comerma-Steffensen, S., Grann, M., Andersen, CU., et al.[2019]

Liraglutide, a GLP-1 receptor agonist, is effective for weight loss in overweight or obese patients, showing greater weight reduction compared to placebo and orlistat, particularly at a dosage of 3 mg daily.

In addition to weight loss, liraglutide has been associated with significant health improvements, including reductions in waist circumference, blood pressure, and better lipid profiles, making it a beneficial option for patients with or without type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide, GLP-1 receptor agonist, for chronic weight loss. Moore, KG., Shealy, K., Clements, JN.[2022]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

Modest weight loss of 5-10% can lead to significant improvements in cardiovascular health for individuals with obesity, highlighting the importance of even small changes in weight.

Recent FDA approvals of medications like phentermine/topiramate ER, lorcaserin, naltrexone SR/bupropion SR, and liraglutide 3.0 mg provide new pharmacologic options for obesity treatment, which is crucial given the rising obesity epidemic in the USA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity. Saunders, KH., Kumar, RB., Igel, LI., et al.[2018]

In a Phase II study involving 413 participants with type 2 diabetes, the dual agonist survodutide significantly reduced HbA1c levels and body weight after 16 weeks of treatment, with the most effective doses being 1.8 mg and 2.7 mg once weekly.

Survodutide showed a greater reduction in body weight compared to semaglutide at higher doses, although gastrointestinal side effects were common, affecting 77.8% of participants, suggesting that careful dose escalation may help manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Blüher, M., Rosenstock, J., Hoefler, J., et al.[2023]

Semaglutide 2.4 mg/week, a GLP-1 receptor analogue, has shown promising results in achieving over 15% weight loss in individuals with obesity, marking a significant advancement in obesity treatment options.

The dual agonist tirzepatide, which targets both GLP-1 and glucose-dependent insulinotropic polypeptide, has demonstrated even greater weight loss potential, suggesting that combining different gut hormone mechanisms could enhance the effectiveness of obesity pharmacotherapy compared to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapies for obesity. Papamargaritis, D., le Roux, CW., Holst, JJ., et al.[2022]

Lifestyle modifications are effective in preventing the progression to type 2 diabetes and can be combined with pharmacological treatments for better outcomes.

Among the medications reviewed, phentermine with topiramate showed the greatest weight reduction (10.2 kg), while liraglutide is notable for its long-term efficacy (up to 3 years) in patients with prediabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity management among patients with type 2 diabetes and prediabetes: a focus on lifestyle modifications and evidence of antiobesity medications. Nguyen, B., Clements, J.[2019]

Citations

1. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/phase-ii-clinical-trial-weight-loss-results

Phase II clinical trial weight loss results Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide (BI 456906)

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39453356/

Survodutide for the Treatment of Obesity SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06077864

NCT06077864 | A Study to Test the Effect of Survodutide ... The purpose of this study is to find out whether people with overweight or obesity who take a medicine called survodutide (BI 456906) are less or more likely ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2401755

A Phase 2 Randomized Trial of Survodutide in MASH and ... Here, we report results from a phase 2 dose-finding trial investigating the efficacy, safety, and side-effect profile of multiple subcutaneous ...

5. jacc.org jacc.org/doi/10.1016/j.jchf.2024.09.004

Survodutide for the Treatment of Obesity: Rationale and ... SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.

6. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/phase-3-studies-survodutide-obesity-and-overweight

Phase 3 studies survodutide obesity and overweight Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38330987/

Glucagon and GLP-1 receptor dual agonist survodutide for ... This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity ...