AZD4831 for Heart Failure

(ENDEAVOR Trial)

Recruiting at 167 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: AstraZeneca

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Chronic kidney disease, Severe pulmonary disease, COVID-19, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

711 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called AZD4831 to see if it can help people with a certain type of heart failure. The study will include people whose hearts pump less efficiently but still have some function left. Researchers want to find out if this medication can improve how well their hearts work and make them feel better.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants taking certain medications known to strongly affect liver enzymes (like itraconazole or rifampicin). It's best to discuss your current medications with the trial team.

What evidence supports the effectiveness of the drug AZD4831 for heart failure?

While there is no direct evidence for AZD4831, studies on similar drugs like candesartan, an angiotensin II receptor antagonist, have shown significant improvements in heart failure symptoms and reduced progression of the disease. ^{1 2 3 4 5}

Eligibility Criteria

Adults aged 40-85 with stable heart failure, not recently worsened, who can walk a bit but not too far and have a left ventricular ejection fraction over 40%. They should be of non-childbearing potential and have a body mass index between 18.0 to 45.0 kg/m2. Excluded are those with severe kidney issues, very low or high blood pressure or heart rate, short life expectancy due to other diseases, allergies to drugs, conditions affecting exercise ability, recent heart problems or certain blood levels outside the normal range.

Inclusion Criteria

You are between 40 and 85 years old, have had stable symptoms of heart failure for at least 1 month, and meet specific criteria for heart function and exercise capacity.

You must be 40-85 years old, have been diagnosed with symptomatic heart failure for at least 6 weeks, have a certain level of heart function, be able to walk a certain distance, and meet specific health assessment criteria based on your weight. You should also be unable to have children.

I am either a man or a woman who cannot become pregnant.

Exclusion Criteria

My condition meets all the same requirements as Part A, except for those about life expectancy, heart failure cause, and lung issues.

Criterion: You have severe kidney problems, high or low blood pressure, fast or slow heart rate, a short life expectancy due to reasons other than heart disease, allergies to certain medications, conditions that limit physical activity, heart failure, low levels of hemoglobin, certain thyroid or liver disorders, severe lung or heart disease, ongoing infections, taking specific medications affecting liver enzymes, or have participated in this study before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive AZD4831 or placebo in Part A of the study

48 weeks

Multiple visits as per study protocol

Treatment Part B

Participants receive AZD4831 or placebo in Part B of the study

48 weeks

Multiple visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AZD4831
• Placebo

Trial Overview The trial is testing AZD4831 against a placebo in people with specific types of heart failure. It's split into two parts: Part A (660 participants) and Part B (820 participants), each lasting up to 48 weeks. The study aims to see if AZD4831 is effective and safe for these patients by comparing it blindly—neither doctors nor patients know who gets the real drug.

Participant Groups

Group I: Part B Dose based on Part A Experimental Treatment 1 Intervention

AZD4831 Dose based on Part A

Group II: Part A 5 mg Experimental Treatment 1 Intervention

AZD4831 5 mg

Group III: Part A 2.5 mg Experimental Treatment 1 Intervention

AZD4831 2.5 mg

Group IV: Part A Placebo Placebo Group 1 Intervention

Placebo

Group V: Part B Placebo Placebo Group 1 Intervention

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 259 patients with advanced heart failure, those hospitalized reported significantly higher symptom burden and psychosocial distress compared to outpatients, indicating a need for better management of these issues.

A high percentage of patients (82% hospitalized and 52% outpatients) met criteria for specialized palliative care support, highlighting the importance of addressing palliative needs even in patients with a relatively good prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study. Strangl, F., Ischanow, E., Ullrich, A., et al.[2023]

In a 6-month study involving 305 patients with heart failure, candesartan significantly reduced the progression of heart failure (7.4% in the candesartan group vs. 22.2% in the placebo group), demonstrating a 63.8% risk reduction.

Candesartan also led to a significant decrease in cardiovascular events (10.8% vs. 22.9% in the placebo group), indicating its efficacy in improving heart health in patients who were either untreated or intolerant to ACE inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of angiotensin II receptor antagonist on heart failure]. Matsumori, A.[2021]

Heart failure (HF) is classified into four types based on left ventricular ejection fraction (LVEF), and despite advancements in treatment, it still has a poor prognosis with high rates of mortality and hospitalization.

Recent large-scale clinical trials have shown that new pharmacological agents, such as sacubitril/valsartan and SGLT2 inhibitors, are effective in improving outcomes for chronic heart failure, highlighting the need for continued development of innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines. Tsutsui, H.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study. [2008]

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

Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy in HFrEF]. [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

[Effect of angiotensin II receptor antagonist on heart failure]. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Recent advances in the pharmacological therapy of chronic heart failure: Evidence and guidelines. [2022]