AZD5004 for Obesity

(VISTA Trial)

Not currently recruiting at 65 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Weight loss drugs

Disqualifiers: Diabetes, Cushing's, Prader-Willi, others

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 a new oral tablet, AZD5004, to evaluate its effectiveness and safety for individuals with obesity or those who are overweight with a related health issue. Researchers aim to determine if taking this tablet daily for 36 weeks can help manage weight in these groups. Participants will be randomly assigned to different groups, with some receiving the active treatment and others a placebo (a pill with no active drug). Ideal candidates are adults with a BMI of 30 or more, or a BMI of 27 or more with conditions like high blood pressure or sleep apnea. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken any weight loss medications in the last 3 months before the study.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are taking any medication for weight loss, you must have stopped 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 AZD5004 is generally safe for use. Studies found its safety profile similar to other treatments with the same mechanism. This means it typically doesn't cause serious side effects. Most participants in the studies did not experience major issues. There were no significant differences in how people felt after taking it compared to other similar treatments. The research supports using AZD5004 for obesity and related conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AZD5004 for obesity because it offers a novel approach compared to current treatments like lifestyle changes, medications such as orlistat, and surgery. Unlike standard options that often focus on fat absorption or appetite suppression, AZD5004 targets specific metabolic pathways to enhance energy expenditure and fat breakdown. This new mechanism of action could potentially lead to more effective weight loss with fewer side effects, making it a promising candidate for those struggling with obesity.

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

Studies have shown promising results for AZD5004, the investigational treatment tested in this trial, in treating obesity. In earlier research, patients lost an average of 5.8% of their body weight after four weeks of treatment. This treatment targets GLP-1 receptors, which help control hunger and blood sugar levels. Early evidence suggests it is effective for both obesity and type 2 diabetes. These findings support the potential of AZD5004 as a helpful treatment for people with obesity. ^{1 2 3 6 7}

Who Is on the Research Team?

Prof Melanie Davies, MBChB MD

Principal Investigator

Diabetes Research Centre Leicester Diabetes Centre - Bloom University of Leicester

Are You a Good Fit for This Trial?

This trial is for adults at least 18 years old who are living with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with at least one weight-related health issue. Key eligibility details will be provided by the study team.

Inclusion Criteria

A stable body weight for 3 months prior to Screening (± 5% body weight change)

My BMI is over 27 and I have a condition like high blood pressure, high cholesterol, heart disease, or sleep apnea.

Exclusion Criteria

I have a history of type 1 or type 2 diabetes.

I have a history of pancreatitis.

I have a severe digestive condition or have had major surgery on my upper GI tract.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD5004 or placebo once daily as an oral tablet for 36 weeks

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AZD5004

Trial Overview

The trial is testing AZD5004, a new oral medication, against a placebo over a period of 36 weeks to see its effects on individuals with obesity or overweight conditions. Participants are randomly assigned to either the drug or placebo group.

How Is the Trial Designed?

Group I: Arm 5 Experimental Treatment 1 Intervention

Active IMP

Group II: Arm 4 Experimental Treatment 1 Intervention

Active IMP

Group III: Arm 3 Experimental Treatment 1 Intervention

Active IMP

Group IV: Arm 2 Experimental Treatment 1 Intervention

Active IMP

Group V: Arm 1 Experimental Treatment 1 Intervention

Active IMP

Group VI: Arm 6 Placebo Group 1 Intervention

Matching placebo for each of the 5 active arms

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 648 obese patients undergoing bariatric surgery, it was found that mutations in the Melanocortin-4 Receptor (MC4R) did not impact weight loss outcomes over one year post-surgery.

Regardless of the type of MC4R mutation or polymorphism, patients experienced similar weight loss compared to matched controls, indicating that these genetic factors do not influence the effectiveness of bariatric surgery for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery. Valette, M., Poitou, C., Le Beyec, J., et al.[2021]

The melanocortin-4 receptor (MC4R) is crucial for regulating body weight, with mutations in this gene linked to both rare monogenic obesity and common obesity, highlighting its importance in energy balance.

Setmelanotide, a novel MC4R agonist, has been developed and shows promise for treating obesity without causing harmful cardiovascular side effects, potentially benefiting both rare and common obesity cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R). Hainer, V., Aldhoon Hainerová, I., Kunešová, M., et al.[2022]

In a study of 243 obese Polish children and adolescents, the contribution of MC4R gene variants to obesity was found to be low, indicating that these genetic factors may not play a significant role in this population's obesity rates.

The research identified six missense and one silent SNPs in the MC4R gene, with only one variant (127L) associated with obesity, suggesting that while some variants may be protective, their overall impact on obesity risk is minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Missense mutations and polymorphisms of the MC4R gene in Polish obese children and adolescents in relation to the relative body mass index. Nowacka-Woszuk, J., Cieslak, J., Skowronska, B., 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]

Bariatric surgery (BS) shows effective short-term weight loss and improved glycemic control in patients with MC4R deficiency, although long-term outcomes can vary significantly based on the type of mutation.

In a study of 6 patients with MC4R-d compared to 8 controls, BS was found to be superior to liraglutide for weight and glycemic control, with no significant difference in weight loss between the two groups at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency. Fojas, EGF., Radha, SK., Ali, T., et al.[2022]

Citations

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These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. Clinical trial registration ...

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This is a Phase IIb, global, randomized, parallel-group, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety ...

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AZD5004/ECC5004, a Small Molecule GLP-1 Receptor ...

Safety and tolerability were in accordance with previous studies6,7 and there was no difference in GI tolerability observed between fed and ...

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ECC5004 has been demonstrated in preclinical studies to possess desirable efficacy and safety profiles. AstraZeneca in CVRM Cardiovascular ...