AZD5004 for Obesity

(VISTA Trial)

Not yet 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: Oral contraceptives, Diabetes medication

Disqualifiers: Type 1 diabetes, T2DM, 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 a new oral treatment called AZD5004 to determine its safety and effectiveness in weight loss. It targets adults who are obese or overweight with at least one weight-related health issue, such as high blood pressure or sleep apnea. Participants must have maintained a stable body weight for the past three months. The trial compares AZD5004 to a placebo, with some participants receiving the treatment and others a non-active pill to measure differences. As a Phase 2 trial, this research focuses on assessing 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, but you cannot have taken weight loss or diabetes medications in the past 3 months before the trial.

Is there any evidence suggesting that AZD5004 is likely to be safe for humans?

Research has shown that AZD5004 is as safe as other similar treatments. It targets GLP-1 receptors, which help control weight. Studies have found that most people tolerate AZD5004 well. Participants experienced no major differences in stomach-related side effects regardless of whether they ate before taking it. Earlier research also suggested it is safe and effective for other conditions, like type 2 diabetes, indicating it might be safe for weight loss too. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for obesity?

AZD5004 is unique because it potentially targets obesity through a novel mechanism of action, unlike current treatments such as appetite suppressants and medications like orlistat or GLP-1 receptor agonists. Researchers are excited about AZD5004 because it may offer a new approach by focusing on a different biological pathway that hasn't been extensively explored in obesity management yet. This could open up new possibilities for individuals who haven't benefited from existing treatments.

What evidence suggests that AZD5004 might be an effective treatment for obesity?

Studies have shown that AZD5004 can lead to significant weight loss. In early trials, patients with type 2 diabetes lost 5.8% of their body weight after just four weeks of treatment. This suggests that AZD5004 could help people who are overweight or obese lose a meaningful amount of weight. The treatment mimics a hormone called GLP-1, which helps control appetite and blood sugar levels. Initial research supports its potential as an effective therapy for obesity and related conditions. ^{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. Specific eligibility details were not provided, so interested individuals should inquire about additional inclusion and exclusion criteria.

Inclusion Criteria

I can sign and understand the consent form.

I cannot become pregnant.

I am using effective birth control that is not the pill during the study.

Exclusion Criteria

Hemoglobin A1c (HbA1c) ≥ 6.5% (48 mmol/mol) at Screening

Cardiac arrhythmia or electrocardiogram (ECG) morphology abnormalities, as considered by the investigator, that may interfere with interpretation of QT interval corrected for heart rate (QTc) interval changes, including ST wave morphology

I have had or plan to have weight loss surgery or a device fitted.

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 study is testing the effects of a new drug called AZD5004 compared to a placebo. Participants will take an oral tablet once daily for 36 weeks in this double-blind study, meaning neither they nor the researchers know who gets the real drug or placebo.

How Is the Trial Designed?

Group I: Arm 5 Experimental Treatment 2 Interventions

00mg dose or placebo

Group II: Arm 4 Experimental Treatment 2 Interventions

00mg dose or placebo

Group III: Arm 3 Experimental Treatment 2 Interventions

00mg dose or placebo

Group IV: Arm 2 Experimental Treatment 2 Interventions

00mg dose or placebo

Group V: Arm 1 Experimental Treatment 2 Interventions

00mg dose or placebo

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 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]

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 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]

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]

Citations

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A Phase IIb randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of AZD5004 in participants living with obesity ...

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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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Non-clinical and first-in-human characterization of ...

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

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The main purpose of this study is to assess the safety, tolerability, and pharmacokinetic (PK) of AZD5004 administered as multiple oral doses in healthy ...

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AstraZeneca Bolsters Obesity Pipeline With Promising ...

The GLP-1 resulted in 5.8% weight loss after four weeks of treatment in type 2 diabetes patients. Pharmacodynamic data showed that all tested ...

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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 ...