Azelaprag + Tirzepatide for Obesity

(STRIDES Trial)

No longer recruiting at 16 trial locations

Overseen By Central Recruiting

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BioAge Labs, Inc.

Must not be taking: GLP-1R agonists, Warfarin

Disqualifiers: Diabetes, Thyroid disease, Liver disease, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new weight management approach for adults aged 55 and older. It examines the effectiveness of combining azelaprag pills, taken once or twice daily, with a weekly injection of tirzepatide for weight loss. The study compares various combinations of these treatments to determine the most effective and assesses their safety. Participants should have a BMI between 30 and 40 and have previously attempted but not succeeded in losing weight through diet. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot participate if you are currently using warfarin, have used weight loss drugs or supplements within 90 days of screening, or have been treated with medications that may cause significant weight gain within 90 days of screening.

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

Studies have raised concerns about the safety of azelaprag. In a recent trial, 11 participants taking azelaprag showed higher liver enzyme levels, indicating potential liver problems. This concern led to the early termination of the study due to liver safety issues.

Research shows that tirzepatide is generally well-tolerated. Participants using tirzepatide experienced significant weight loss without major safety issues.

Considering both treatments together is important. Researchers studied the combination of azelaprag and tirzepatide for weight loss. However, due to safety concerns with azelaprag, caution and informed decision-making are crucial when considering participation in a trial involving this drug. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Azelaprag and Tirzepatide for obesity because these treatments offer unique approaches compared to current options. Azelaprag is a novel drug that works by targeting specific hormonal pathways involved in appetite regulation, which is different from many existing treatments that primarily focus on altering metabolism or inhibiting fat absorption. Tirzepatide, on the other hand, is a once-weekly injectable that combines the action of two incretin hormones, offering enhanced glucose and weight control. Together, these treatments have the potential to provide more effective weight management by addressing both appetite and metabolic regulation in a comprehensive way.

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

Research has shown that tirzepatide, which participants in this trial may receive, can help people lose a significant amount of weight. In earlier studies, participants using tirzepatide lost between 16.5% and 22.4% of their body weight over 72 weeks. Initial results suggest that adding azelaprag, another treatment option in this trial, might lead to even more weight loss and improved body and muscle health. In animal studies, azelaprag nearly doubled the weight loss seen with similar drugs. These findings suggest that combining azelaprag and tirzepatide, as tested in this trial, could be highly effective for weight management. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 55 and over who are dealing with obesity. Participants must be willing to take oral medication daily or twice a day, receive weekly injections, and commit to the study schedule including follow-ups.

Inclusion Criteria

History of at least 1 self-reported unsuccessful dietary effort to lose body weight

BMI between 30 and 40 kg/m2 inclusive at the time of screening

I am 55 years old or older.

Exclusion Criteria

Lifetime history of a suicide attempt

Known clinically significant gastric emptying abnormality

I have had gallbladder problems in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral azelaprag and/or tirzepatide for weight management

24 weeks

Visits every 2 weeks for the first 8 weeks, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Azelaprag
• Tirzepatide

Trial Overview The effectiveness of combining a new oral drug called Azelaprag (taken once or twice daily) with Tirzepatide (a weekly injection) for weight management in older adults is being tested against using Tirzepatide alone.

How Is the Trial Designed?

Group I: D: Azelaprag Monotherapy Experimental Treatment 2 Interventions

* Azelaprag 300mg every morning * Azelaprag 300mg every evening * Tirzepatide placebo once weekly

Group II: C: Azelaprag twice daily plus Tirzepatide Experimental Treatment 2 Interventions

* Azelaprag 300mg every morning * Azelaprag 300mg every evening * Tirzepatide 5mg once weekly

Group III: B: Azelaprag once daily plus Tirzepatide Experimental Treatment 3 Interventions

* Azelaprag 300mg every morning * Azelaprag placebo every evening * Tirzepatide 5mg once weekly

Group IV: A: Tirzepatide Monotherapy Active Control 2 Interventions

* Azelaprag placebo every morning * Azelaprag placebo every evening * Tirzepatide 5mg once weekly

Who Is Running the Clinical Trial?

BioAge Labs, Inc.

Lead Sponsor

Trials

5

Recruited

410+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Tirzepatide demonstrated a dose-dependent ability to lower HbA1c levels in adults with type 2 diabetes, with reductions ranging from -17.71 to -22.35 mmol/mol compared to placebo, and was also more effective in reducing body weight than other treatments.

While tirzepatide did not increase the risk of hypoglycaemia compared to placebo and showed lower rates than basal insulin, it was associated with a higher incidence of gastrointestinal side effects, particularly nausea and vomiting, especially at the 15 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Karagiannis, T., Avgerinos, I., Liakos, A., et al.[2023]

The SURMOUNT 2 trial demonstrated that tirzepatide, a GIPR:GLP-1R co-agonist, shows unprecedented weight loss efficacy in patients with obesity and type 2 diabetes, suggesting a significant advancement in anti-obesity treatments.

This trial highlights the potential of tirzepatide to achieve weight loss results that were previously thought to be nearly impossible, marking a new era in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SURMOUNTing body weight barriers in type 2 diabetes. Novikoff, A., Müller, TD.[2023]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Tirzepatide, a dual GLP-1/GIP receptor co-agonist, has been shown to significantly reduce glycosylated hemoglobin levels (1.87% to 3.02%) and body weight (5.4 to 12.9 kg) in people with type 2 diabetes over treatment periods of up to 104 weeks, demonstrating its efficacy compared to placebo and other diabetes medications.

In individuals without diabetes, tirzepatide also led to substantial weight loss (16.5% to 22.4%) over 72 weeks, indicating its potential for obesity management as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Sinha, R., Papamargaritis, D., Sargeant, JA., et al.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Tirzepatide is a new drug that activates both the GIP and GLP-1 receptors, leading to improved blood sugar control and significant weight loss, making it a promising treatment for obesity and diabetes.

This dual receptor activation enhances insulin sensitivity and lipid metabolism while potentially causing fewer side effects compared to traditional GLP-1 receptor agonists, as supported by various studies including in vitro, animal, and human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist on weight loss in subjects with obesity. Zaffina, I., Pelle, MC., Armentaro, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06515418

NCT06515418 | Efficacy and Safety of Oral Azelaprag Plus ... The primary endpoint will be the effect on body weight reduction as measured by mean percent change in body weight at 24 weeks in participants that received ...

2. ir.bioagelabs.com ir.bioagelabs.com/news-releases/news-release-details/bioage-labs-announces-discontinuation-strides-phase-2-clinical

BioAge Labs Announces Discontinuation of STRIDES Phase ... The trial was designed to evaluate the efficacy as measured by body weight reduction and other outcomes, safety, and tolerability of two oral ...

3. diabetesjournals.org diabetesjournals.org/diabetes/article/73/Supplement_1/118-OR/154974/118-OR-The-Apelin-Receptor-Agonist-Azelaprag

118-OR: The Apelin Receptor Agonist Azelaprag Increases ... Addition of azelaprag to incretin regimens increased weight loss while restoring body composition and muscle function relative to monotherapy.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/bioage-halts-phase-ii-obesity/

BioAge halts Phase II STRIDES trial of obesity drug In the trail, 11 participants in the azelaprag group exhibited transaminase elevations without significant symptoms. December 9, 2024.

5. bariatricnews.net bariatricnews.net/post/bioage-axes-strides-trial-evaluating-azelaprag-in-combination-with-tirzepatide-for-the-treatment-of

BioAge axes STRIDES trial evaluating azelaprag in ... The trial was designed to evaluate the efficacy as measured by body weight reduction and other outcomes, safety, and tolerability of two oral ...

6. medthority.com medthority.com/news/2024/12/strides-phase-ii-study-of-azelaprag-as-monotherapy-and-in-combination-with-tirzepatide-for-obesity--is-discontinued.-bioage-labs

STRIDES Phase II study of azelaprag for obesity is ... BioAge Labs has discontinued the Phase II STRIDES study of azelaprag for obesity due to liver safety concerns.