Alirocumab for Heart Transplant Rejection

(CAVIAR Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Disqualifiers: Impaired liver function

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 26

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the medication alirocumab is safe and effective for individuals who have recently undergone a heart transplant. Alirocumab, a PCSK9 inhibitor, helps manage cholesterol levels, and the study aims to determine if it can prevent heart vessel problems common after a transplant. Participants will receive either alirocumab or a placebo, a substance with no active medication, for one year. This trial suits heart transplant recipients without liver function issues. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that alirocumab, a type of medication, is generally safe and well-tolerated. It effectively lowers LDL cholesterol, often called the "bad" cholesterol, in people who have had heart transplants. This is important because high cholesterol can lead to heart issues. Alirocumab has been safely used for other conditions for up to five years, indicating that most people handle it well. Side effects are minimal, so few people experience serious problems when taking it. Overall, alirocumab appears to be a safe option for managing cholesterol in heart transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about alirocumab for heart transplant rejection because it offers a novel approach compared to current treatments. Most existing treatments focus on suppressing the entire immune system, which can lead to significant side effects. However, alirocumab is a monoclonal antibody that specifically targets and lowers LDL cholesterol, which might play a role in transplant rejection. This targeted action could potentially reduce rejection rates with fewer side effects. Additionally, alirocumab is administered via a simple subcutaneous injection every two weeks, offering convenience to patients.

What evidence suggests that alirocumab might be an effective treatment for heart transplant rejection?

In this trial, participants will receive either alirocumab or a placebo. Research has shown that alirocumab effectively lowers cholesterol levels in heart transplant patients. Studies have found it can reduce "bad" LDL cholesterol by about 66.6%, which is crucial for heart health. Alirocumab also prevents excessive thickening of blood vessel walls, a common issue after heart transplants, with few side effects. This prevention is important because it may help avoid cardiac allograft vasculopathy, a frequent complication post-transplant. Overall, alirocumab's ability to lower cholesterol and stabilize blood vessels offers hope for reducing complications in heart transplant recipients. ^{1 2 6 7 8}

Who Is on the Research Team?

William Fearon, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals who have recently received a heart transplant. Participants must not have impaired liver function to be eligible.

Inclusion Criteria

I have received a heart transplant.

Exclusion Criteria

My liver isn't working properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alirocumab or placebo every other week for one year following heart transplantation

52 weeks

26 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alirocumab

Trial Overview The study tests the safety and effect of alirocumab, a PCSK9 inhibitor, on preventing blood vessel disease in the new heart compared to a placebo (inactive substance).

How Is the Trial Designed?

Group I: alirocumab Experimental Treatment 1 Intervention

alirocumab 150mg subcutaneous every other week for one year following start of study drug

Group II: placebo Placebo Group 1 Intervention

placebo to match alirocumab every other week for one year following start of study drug

Alirocumab is already approved in European Union, United States for the following indications:

Approved in European Union as Praluent for:

• High cholesterol - Familial Homozygous
• Cardiovascular Risk Reduction
• High cholesterol - Familial Heterozygous
• High Cholesterol

Approved in United States as Praluent for:

• High cholesterol - Familial Homozygous
• Cardiovascular Risk Reduction
• High cholesterol - Familial Heterozygous
• Primary hyperlipidemia

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. nature.com nature.com/articles/s41598-025-22916-0

PCSK9 inhibitors in the management of ... It is worth noting that the post alirocumab LDL level of 1.86 ± 0.89mmol/L achieved in this audit still exceeds the ideal target of 1.4mmol/L ...

2. pharmacytimes.com pharmacytimes.com/view/pcsk9-inhibitors-found-safe-effective-in-solid-organ-transplant-recipients

PCSK9 Inhibitors Are Found Safe, Effective in Solid Organ ... Evolocumab was found to have the highest likelihood of LDL-C reduction (67.2%), followed by alirocumab (66.6%) and tafolecimab (65.7%). For CVE ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916421001135

PCSK9 Inhibitors in Heart Transplant Patients Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects.

4. jacc.org jacc.org/doi/10.1016/j.jchf.2024.04.026

Randomized Trial of Cholesterol Lowering With ... Twelve months of treatment with evolocumab substantially reduced LDL cholesterol but did not reduce maximal coronary intimal thickness in heart ...

5. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.062788

Immune Regulation of the Liver Through the PCSK9/CD36 ... Our data suggest that the PCSK9/CD36 pathway is a potential clinical target to protect against transplant rejection. Heart transplantation is ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30650126/

Treatment of hypercholesterolaemia with PCSK9 inhibitors ... Our study demonstrates that the PCSK9 inhibitors Evolocumab and Alirocumab lead to a significant reduction of LDL Cholesterol in heart transplantation ...

7. trialx.com trialx.com/clinical-trials/listings/264353/efficacy-and-safety-of-alirocumab-to-prevent-early-cardiac-allograft-vasculopathy-in-recent-heart-transplant-recipients/

Efficacy and Safety Of Alirocumab to Prevent Early Cardiac ... Although heart transplant recipients fulfill approved indication and standard clinical guidelines of a PCSK9 inhibitor, alirocumab, there are no available data ...

8. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.029216

Long‐Term Efficacy, Safety, and Tolerability of Alirocumab ... Thus, alirocumab appears to be a safe, well‐tolerated, and effective lipid‐modifying and outcome‐improving treatment when used for up to 5 years ...