AZD9550 + AZD6234 for Obesity

(ASCEND Trial)

Not currently recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, AZD9550 and AZD6234, to determine if they aid weight loss more effectively than a placebo or each treatment individually. It targets individuals living with obesity or who are overweight and have another weight-related health issue, such as high blood pressure or sleep apnea. Participants should have maintained a stable weight for the past three months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in weight loss treatments.

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.

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

Research has shown that AZD9550 and AZD6234 are generally safe for people. Studies have found that AZD9550 is safe for individuals who are overweight or have obesity, with participants tolerating increasing doses without major issues. Similarly, AZD6234 has been tested in adults with obesity and found to be safe, even with repeated doses.

For those considering the combined use of AZD9550 and AZD6234, early results suggest this combination is also manageable. This trial remains in the early stages, so the researchers are still collecting safety data, but both treatments have shown promise in earlier studies. Participants in past studies have reported minor side effects, but nothing serious has been consistently observed.

Overall, while more data is needed to confirm long-term safety, early evidence is encouraging for both AZD9550 and AZD6234, whether used alone or together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD9550 and AZD6234 for obesity because they offer a fresh approach compared to current treatments like lifestyle changes, medications such as orlistat, or even surgical options. Unlike existing medications that primarily work by reducing fat absorption or suppressing appetite, these investigational drugs may target specific pathways involved in metabolism and fat storage, potentially leading to more effective weight management. Additionally, the trial explores various dosing combinations, which could fine-tune their effectiveness and tailor treatments to individual needs, promising a more personalized approach to tackling obesity.

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

Research has shown that using AZD9550 and AZD6234 together may aid in weight loss. In this trial, participants will receive different combinations of AZD9550 and AZD6234 at varying doses, or placebos, to evaluate their effectiveness. Studies have found that AZD6234 alone leads to significant weight loss compared to a placebo. AZD9550 also showed promising results in early studies, indicating it might help reduce weight. This trial tests the combination of these two drugs because they might work better together than separately, potentially offering a stronger effect on weight loss. Initial findings suggest that this combination could be a powerful option for people struggling with obesity and related conditions. ^{1 4 6 7 8}

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

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06851858

Study Details | NCT06851858 | Efficacy, Safety and ... The study is being conducted across sites in the USA to evaluate the efficacy, safety, and tolerability of AZD6234 in adults with overweight or obesity and type ...

2. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8460C00004

A weight loss study evaluating subcutaneous treatment ... The purpose of this study is to determine whether treatment with AZD9550 when given in combination with AZD6234 as once weekly subcutaneous (SC) injections ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/579696

Efficacy, Safety and Tolerability of AZD6234 in Participants ... Weight loss ≥ 10% from baseline at Study Week 26 (From baseline to week 26) · Absolute change in body weight (kg) from baseline at Study Week 26 ...

4. astrazeneca.com astrazeneca.com/content/dam/az/Investor_Relations/events/Weight-Management-Virtual-Event-IR-presentation.pdf

Weight Management Virtual Event Presented at Obesity Week 2024. Phase I SAD demonstrated efficacy with promising tolerability. AZD6234 | LA amylin. Body weight change after ...

5. finance.yahoo.com finance.yahoo.com/news/astrazenecas-obesity-pills-revealed-positive-163641942.html

AstraZeneca's Obesity Pills Revealed Positive Result In ... Efficacy: AZD6234 showed a statistically significant reduction in body weight compared to placebo. Market Position: AZD6234 is positioned ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8750C00002

A study to assess the safety, tolerability, pharmacokinetics ... A study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD6234 after repeat dose administration in participants who are ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06132841

NCT06132841 | A Study to Assess the Safety, Tolerability ... The safety and tolerability of repeated subcutaneous (SC) doses of AZD6234 compared to placebo will be assessed. From Screening (Day -35 to Day -3) to Day 78 ( ...

8. reuters.com reuters.com/business/healthcare-pharmaceuticals/astrazeneca-says-experimental-obesity-pill-safe-tolerable-early-stage-trial-2024-11-04/

AstraZeneca says experimental obesity pill safe in early- ... AstraZeneca (AZN.L) said on Monday its experimental weight-loss pill, licensed a year ago from China's Eccogene for up to $2 billion, was safe and tolerable in ...