AZD5004 for Obesity

(VISTA Trial)

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

285 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase IIb, global, randomized, parallel-group, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of AZD5004 compared with placebo, given once daily as an oral tablet(s) for 36 weeks, in male and female participants at least 18 years of age who are living with obesity (body mass index \[BMI\] ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) who have at least 1 weight-related comorbidity

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.

How is the drug AZD5004 different from other obesity treatments?

AZD5004 (ECC5004) is unique because it may target the melanocortin-4 receptor (MC4R), which plays a key role in regulating body weight by affecting appetite and energy expenditure. This approach could be particularly beneficial for individuals with specific genetic variations in the MC4R gene, offering a more personalized treatment option compared to standard obesity therapies. ^{1 2 3 4 5}

Research Team

Prof Melanie Davies, MBChB MD

Principal Investigator

Diabetes Research Centre Leicester Diabetes Centre - Bloom University of Leicester

Eligibility Criteria

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 am at least 18 years old.

I can sign and understand the consent form.

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

I have taken diabetes medication in the last 3 months.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

References

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. Switzerland pubmed.ncbi.nlm.nih.gov

Weight and Glycemic Control Outcomes of Bariatric Surgery and Pharmacotherapy in Patients With Melanocortin-4 Receptor Deficiency. [2022]

3. England 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. [2022]

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

Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery. [2021]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

Melanocortin pathways: suppressed and stimulated melanocortin-4 receptor (MC4R). [2022]