AZD5004 for Obesity

(VISTA Trial)

Recruiting at 62 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

310 Participants Needed

Trial Summary

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.

How does the drug AZD5004 differ from other obesity treatments?

AZD5004 is unique because it may target the melanocortin-4 receptor (MC4R), which plays a key role in regulating body weight by affecting energy balance. 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}

How is the drug AZD5004 different from other obesity treatments?

AZD5004 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 affecting the MC4R pathway, offering a more personalized treatment option compared to standard obesity therapies. ^{1 2 3 4 5}

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

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. 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

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 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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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

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

2. Germany pubmed.ncbi.nlm.nih.gov

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

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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