AZD5462 for Heart Failure

(LUMINARA Trial)

Not currently recruiting at 62 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Heart failure medications

Disqualifiers: Myocardial infarction, Stroke, Sarcoidosis, 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: 12

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how AZD5462, a potential new drug, affects heart function in individuals with chronic heart failure, a condition where the heart fails to pump blood effectively. Participants will receive varying doses of AZD5462 or a placebo (a non-active pill) for 24 weeks to compare outcomes. Individuals who have managed heart failure with consistent medication for at least four weeks and experience symptoms like breathlessness or fatigue may qualify. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires participants to be on stable heart failure medication for at least 4 weeks before joining and during the screening period, so you will not need to stop your current heart failure medications.

Is there any evidence suggesting that AZD5462 is likely to be safe for humans?

Research has shown that AZD5462 was generally well tolerated in earlier studies. In one study, participants took different doses of AZD5462 without any serious problems, indicating that the treatment can be safely administered at various dose levels. The safety information from these studies supports further testing of AZD5462 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 AZD5462 for heart failure because it offers a novel approach compared to standard treatments like ACE inhibitors, beta-blockers, and diuretics. Unlike these traditional therapies, AZD5462 works by targeting a different pathway that may reduce heart stress more effectively. Additionally, this treatment is given as an oral tablet once daily, potentially making it more convenient for patients. This new mechanism and ease of use have the potential to improve outcomes for those with heart failure.

What evidence suggests that AZD5462 could be an effective treatment for heart failure?

Research has shown that AZD5462 might be a promising treatment for heart failure. This trial will evaluate AZD5462 at low, medium, and high doses, along with a placebo group. The drug activates a specific part of the heart called RXFP1, which may help the heart function better. Studies have found that AZD5462 was well tolerated at various doses, indicating its safety for continued use. While detailed results on its effectiveness for heart failure are still being gathered, the drug's mechanism offers hope for improved heart function. Early findings suggest it could support heart health in people with chronic heart failure. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with chronic heart failure (NYHA FC II to IV) who have been on stable heart medications for at least 4 weeks. Participants must have a BMI of at least 18 and agree to contraception or abstinence measures during the study and for three months after.

Inclusion Criteria

I agree not to father a child or donate sperm for 3 months after the study ends.

I have been diagnosed with heart failure that affects my daily activities.

Minimum body mass index (BMI) of 18 kg/m^2 at Screening

Exclusion Criteria

I have not had significant heart, liver, or lung issues, or cancer in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

at least 1 study visit

Treatment

Participants receive a once daily dose of AZD5462 or placebo for 24 weeks

24 weeks

8 study visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

3 study visits

What Are the Treatments Tested in This Trial?

Interventions

• AZD5462

Trial Overview The study tests AZD5462's effects on cardiac function in chronic heart failure patients, comparing it against a placebo. The goal is to see if AZD5462 can improve heart performance.

How Is the Trial Designed?

Group I: Cohort A & B: Placebo Experimental Treatment 1 Intervention

Participants will receive matching placebo OD tablets for 24 weeks.

Group II: Cohort A & B: AZD5462 medium dose Experimental Treatment 1 Intervention

Participants will receive medium dose of AZD5462 as OD tablets for 24 weeks.

Group III: Cohort A & B: AZD5462 low dose Experimental Treatment 1 Intervention

Participants will receive low dose of AZD5462 as OD tablets for 24 weeks.

Group IV: Cohort A & B: AZD5462 high dose Experimental Treatment 1 Intervention

Participants will receive high dose of AZD5462 as OD tablets for 24 weeks.

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 25 patients with severe chronic congestive heart failure (CHF), adding pimobendan to their existing treatment led to sustained improvement in heart function for many, despite some experiencing episodes of CHF that required intravenous therapy.

The median survival for patients receiving pimobendan was 12 months, with some patients living over 3 years, indicating that pimobendan can be an effective add-on therapy for those not responding to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intractable heart failure despite angiotensin-converting enzyme inhibitors, digoxin, and diuretics: long-term effectiveness of add-on therapy with pimobendan. Hagemeijer, F.[2019]

Vesnarinone, a new treatment for advanced congestive heart failure, shows promise in improving heart function and quality of life for patients with severe symptoms, particularly those who do not respond to standard treatments.

However, its use comes with a cautionary note, as high doses have been linked to an increased risk of mortality, highlighting the need for careful assessment of risks and benefits before starting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characteristics of vesnarinone. Feldman, AM.[2020]

Pimobendan, a calcium-sensitizing inotropic agent, has been shown to significantly improve exercise capacity and quality of life in patients with advanced heart failure, based on data from five controlled, randomized trials.

Unlike other inotropic agents like milrinone and enoximone, which have shown adverse effects, pimobendan's unique mechanism of action may contribute to its safety and efficacy, warranting further research on its impact on overall mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Kubo, SH.[2018]

Pimobendan has been shown to improve quality of life and increase median survival times in dogs with congestive heart failure (CHF) due to conditions like dilated cardiomyopathy and myxomatous valvular disease, based on multiple blinded, randomized clinical trials.

While most studies report positive outcomes, there are potential adverse effects associated with Pimobendan, prompting ongoing research to further evaluate its safety and efficacy in canine cardiac disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimobendan and its use in treating canine congestive heart failure. Bowles, D., Fry, D.[2011]

ACE inhibitors are the most effective class of drugs for improving survival in chronic heart failure patients, regardless of the disease stage, and are currently being studied for their dose-effect relationship.

While beta-blockers enhance quality of life and physical performance, they have not shown a mortality benefit, and phosphodiesterase inhibitors, despite improving quality of life, are associated with increased mortality and are not recommended for heart failure treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of chronic heart failure: current views]. Komajda, M.[2009]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06299826

NCT06299826 | A Phase IIb Study of AZD5462 in Patients ... The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF). Detailed Description.

2. academic.oup.com academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.976/7393723

Safety, tolerability, and pharmacokinetics of AZD5462, a small ... AZD5462 was generally well tolerated at all dose levels in this phase 1 study. These data pave the way for development of a chronic oral relaxin ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9090C00008

A Phase IIb Study of AZD5462 in Patients with Chronic ... The main purpose of this study is to evaluate the effect of AZD5462 on cardiac function in participants with chronic heart failure (HF).

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38502782/

Discovery of Clinical Candidate AZD5462, a Selective Oral ... Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. J Med Chem. 2024 Mar 28;67(6):4419-4441.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38509642/

Cost-effectiveness of dapagliflozin for patients with heart ... Conclusions: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a ...

6. pubs.acs.org pubs.acs.org/doi/abs/10.1021/acs.jmedchem.3c02184

Discovery of Clinical Candidate AZD5462, a Selective Oral ... AZD5462 is a small molecule pharmacological mimetic of relaxin H2 signaling at RXFP1 and holds promise as a potential therapeutic approach to treat heart ...