AZD9550 + AZD6234 for Obesity

(ASCEND Trial)

Recruiting at 21 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: GLP1

Disqualifiers: Diabetes, GI disease, Psychosis, 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: Unknown

Duration: 36 weeks

374 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to determine whether treatment with AZD9550 when given in combination with AZD6234 as once weekly subcutaneous (SC) injections is superior to placebo or either agent administered as monotherapy for weight loss in participants living with obesity or overweight with at least one weight-related co-morbidity.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on a GLP1 medication, you must stop it at least 3 months before joining the trial.

How does the drug AZD9550 + AZD6234 for obesity differ from other treatments?

The drug AZD9550 + AZD6234 for obesity is unique because it combines two components, potentially offering a novel mechanism of action compared to existing treatments. While specific details about its mechanism are not provided, it may involve targeting multiple pathways, similar to other multireceptor agonists like LY3437943, which targets glucagon, GIP, and GLP-1 receptors to manage weight and improve metabolic health. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for individuals who are overweight or obese and have at least one weight-related health issue. Participants will receive weekly subcutaneous injections and must not be taking other weight loss medications.

Inclusion Criteria

Has your weight stayed within about 10 pounds during the last 3 months?

Exclusion Criteria

Have you had a heart attack, stroke, heart failure, or very high blood pressure in the past 6 months?

Has a doctor told you that you have Type 1 diabetes or poorly controlled Type 2 diabetes (A1C over ~9 %)?

Have you had, or are you planning, weight-loss surgery such as gastric bypass or sleeve?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD9550 and AZD6234 in combination or as monotherapy for weight loss

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AZD6234
• AZD9550

Trial Overview The study tests if a combination of two drugs, AZD9550 and AZD6234, given as weekly shots, is more effective for weight loss than placebo or either drug alone in people with obesity or overweight conditions.

How Is the Trial Designed?

Group I: Arm 9 Experimental Treatment 2 Interventions

AZD6234 high dose or placebo

Group II: Arm 8 Experimental Treatment 2 Interventions

AZD9550 high dose or placebo

Group III: Arm 7 Experimental Treatment 3 Interventions

AZD9550 medium dose + AZD6234 high dose or placebos

Group IV: Arm 6 Experimental Treatment 3 Interventions

AZD9550 high dose + AZD6234 medium dose or placebos

Group V: Arm 5 Experimental Treatment 3 Interventions

AZD9550 medium dose + AZD6234 low dose or placebos

Group VI: Arm 4 Experimental Treatment 3 Interventions

AZD9550 low dose + AZD6234 medium dose or placebos

Group VII: Arm 3 Experimental Treatment 3 Interventions

AZD9550 high dose + AZD6234 high dose or placebos

Group VIII: Arm 2 Experimental Treatment 3 Interventions

AZD9550 medium dose + AZD6234 medium dose or placebos

Group IX: Arm 1 Experimental Treatment 3 Interventions

AZD9550 low dose + AZD6234 low dose or placebos

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study of 59 Chinese patients with morbid obesity, 10 individuals were found to have six different mutations in the MC4R gene, with a prevalence of 16.9% among this group, indicating a significant genetic factor in obesity.

Patients with rare MC4R variants, such as R165W and G233S, showed substantial weight loss after metabolic surgery, suggesting that personalized treatment based on genetic variants can enhance surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery. Gong, Y., Wu, Q., Huang, S., et al.[2023]

LY3437943 is a novel triple agonist that targets three receptors related to metabolism, showing promising results in obese mice by reducing body weight and improving blood sugar control.

In a phase 1 study, LY3437943 demonstrated a safety profile similar to existing treatments and supported once-weekly dosing, with weight loss effects lasting up to 43 days after a single dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun, T., Urva, S., Roell, WC., et al.[2022]

In a study of 682 morbidly obese patients who underwent Swedish adjustable gastric band surgery, those with type 2 diabetes mellitus (T2DM) experienced an average excess weight loss of 38% over a median follow-up of 12.5 months, leading to significant improvements in blood sugar levels and hemoglobin A1c.

The study found that 81% of patients on oral hypoglycemic agents saw remission or improvement in their T2DM, with early intervention (less than 5 years of T2DM before surgery) greatly increasing the likelihood of remission. Additionally, no patients with impaired glucose tolerance progressed to diabetes, suggesting potential preventive benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric banding for the treatment of type 2 diabetes mellitus in morbidly obese. Brancatisano, A., Wahlroos, S., Matthews, S., et al.[2011]

Phentermine/topiramate ER was found to be the most effective weight loss medication among the four new agents, with the highest average weight loss and the greatest percentage of patients achieving significant weight loss (≥5% and ≥10%).

While all four medications have different side effects, liraglutide had the highest rates of gastrointestinal issues, and no clear first-line treatment was established, suggesting that choices should be tailored to individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of New Pharmacological Agents for the Treatment of Obesity. Nuffer, W., Trujillo, JM., Megyeri, J.[2018]

Liraglutide, a diabetes medication, has gained approval in both the US and Europe for obesity treatment and is expected to be widely accepted due to its efficacy.

New research is focusing on activating brown adipose tissue to enhance thermogenesis and developing drugs that mimic gut hormones to achieve results similar to bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Horizons in the Pharmacotherapy of Obesity. Arch, JR.[2018]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery. [2023]

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

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. [2022]

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

Gastric banding for the treatment of type 2 diabetes mellitus in morbidly obese. [2011]

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

A Comparison of New Pharmacological Agents for the Treatment of Obesity. [2018]

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

Horizons in the Pharmacotherapy of Obesity. [2018]