AZD4831 for Heart Failure

(ENDEAVOR Trial)

Recruiting at 211 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD4831 for individuals with heart failure who retain more than 40% heart function. The trial aims to determine if this treatment can improve symptoms and overall heart health over approximately one year. Participants will receive either the treatment or a placebo to compare outcomes. Individuals experiencing heart failure symptoms and taking regular heart medication might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AZD4831 is generally safe for people with heart failure. In studies, patients whose hearts pumped normally (with a left ventricular ejection fraction over 40%) experienced no major safety issues with AZD4831. Specifically, the treatment did not cause any serious or unexpected side effects. Participants tolerated it well, without significant problems that led to discontinuation. This is encouraging for those considering joining a trial with AZD4831 for heart failure. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Researchers are excited about AZD4831 for heart failure because it offers a unique approach compared to current treatments. Unlike standard therapies that generally focus on managing symptoms or improving heart function, AZD4831 targets myeloperoxidase, an enzyme linked to inflammation and oxidative stress in heart failure. This novel mechanism of action could potentially slow disease progression by addressing underlying causes rather than just alleviating symptoms. The treatment's ability to intervene at this molecular level is what sets it apart and generates hope for better long-term outcomes for patients with heart failure.

What evidence suggests that AZD4831 might be an effective treatment for heart failure?

Research has shown that AZD4831 offers promising results for treating heart failure. This treatment blocks myeloperoxidase, an enzyme that can harm the heart. In earlier studies, AZD4831 reduced this enzyme's activity by more than 50% from the starting level and by 75% compared to a placebo. Another study found a 69% reduction in enzyme activity for those taking AZD4831. These findings suggest that AZD4831 could improve heart function and symptoms in people with heart failure. Participants in this trial will receive either AZD4831 at varying doses or a placebo to further evaluate its effectiveness. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1071916423001422

Myeloperoxidase Inhibition in Heart Failure With Preserved ... AZD4831 reduced normalized ex vivo myeloperoxidase specific activity by more than 50% from baseline and by 75% vs placebo in this randomized, double-blind, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04986202

NCT04986202 | Study to Evaluate the Efficacy and Safety ... This is a randomised, double-blind, placebo-controlled, multi-center sequential phase 2b and Phase 3 study to evaluate the efficacy and safety of AZD4831.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10592288/

a sequential phase 2b–3 randomized clinical trial to evaluate ... A sequential phase 2b–3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure

4. astrazeneca.com astrazeneca.com/media-centre/medical-releases/astrazenecas-investigational-mpo-inhibitor-azd4831-shows-promise-in-patients-with-heart-failure-and-a-preserved-ejection-fraction.html

AstraZeneca's investigational MPO inhibitor AZD4831 ... Findings from a planned interim analysis of the SATELLITE trial showed a 69% (95% CI: 36.3, 85.0) reduction in MPO activity in the AZD4831 group ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10915730/

The myeloperoxidase inhibitor mitiperstat (AZD4831) does ... Mitiperstat is a myeloperoxidase inhibitor in clinical development for treatment of patients with heart failure and preserved or mildly reduced ejection ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32770730/

Early Clinical Experience With AZD4831, A Novel ... ... AZD4831, no clinically relevant safety and tolerability findings were observed. ... AZD4831 in patients with heart failure with preserved ejection fraction.

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6580C00003

Safety and tolerability study of AZD4831 in patients with ... A randomized, double-blind, placebo-controlled, parallel group, multicentre study in patients with Heart Failure with preserved Ejection Fraction (HFpEF).