Efficacy and Safety of Alirocumab in Preventing Early Cardiac Allograft Vasculopathy in Recent Heart Transplant Recipients

The primary objective of this study is to assess the **efficacy** of alirocumab in lowering LDL-cholesterol in recent heart transplant recipients, as an adjunct to standard background lipid-lowering therapy with atorvastatin 10 mg daily. This evaluation is clinically relevant as managing LDL-cholesterol levels is crucial in preventing cardiac allograft vasculopathy, a common complication post-heart transplantation. The study will also evaluate the impact of alirocumab on other lipid profile parameters, including total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, lipoprotein a, and triglyceride levels, over a period of 1 to 12 months post-transplantation.

Secondary objectives include: - Evaluating the safety of alirocumab compared to placebo in recent heart transplant recipients. - Assessing changes in coronary artery wall structure using optical coherence tomography (OCT) at 1 and 12 months post-transplantation. - Evaluating the effect of alirocumab on LDL-C and other lipid profile parameters at each visit compared to placebo. - Assessing changes in LDL-C and other lipid profile parameters in the alirocumab group between the end of treatment and the end of the study to evaluate lipid level rebound.

The clinical trial involves participants who are recent heart transplant recipients, specifically addressing **cardiac allograft vasculopathy**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have undergone heart transplantation surgery 3 to 8 weeks prior to the baseline visit. The trial does not focus on a vulnerable population, and participants must be capable of understanding and complying with study procedures throughout the trial duration. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on their recent heart transplant status and willingness to participate, with informed consent obtained from each subject or their legal representative. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** and safety of **alirocumab** in preventing early cardiac allograft vasculopathy in recent heart transplant recipients. This is a randomized, double-blind, controlled trial involving the administration of alirocumab or a placebo as an adjunct to standard lipid-lowering therapy with atorvastatin. The trial will assess the impact of alirocumab on lowering LDL-cholesterol and other lipid profile parameters, including total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, lipoprotein a, and triglyceride levels. The study will be conducted over a period of approximately six years, with an estimated recruitment start date of June 1, 2019, and an estimated end date of May 31, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being a new cardiac transplant recipient aged 18 years or older, having undergone heart transplantation surgery 3-8 weeks prior, and providing written informed consent. Following the screening, participants will attend multiple treatment visits where the primary and secondary endpoints will be assessed. These visits will evaluate the mean levels of LDL-C, HDL-C, TC, TG, ApoB, Lp[a], and ApoA1, as well as the percent change from baseline in calculated LDL-C and differences in other lipids and lipoproteins. The end-of-study visit will mark the conclusion of the participant's involvement in the trial.

The expected length of participant involvement is approximately 12 months, with the treatment period extending up to 15 months. Conditions that may lead to early termination from the study include non-compliance with study procedures or withdrawal of consent. The trial aims to provide valuable insights into the potential benefits of alirocumab in managing lipid levels and preventing cardiac complications in heart transplant recipients.

The clinical trial involves the administration of **Alirocumab**, an experimental medication formulated as a **solution for injection**. Alirocumab is a protein-based therapeutic agent, specifically classified under "Protein - Other." The medication is administered via the **subcutaneous** route. The dosing regimen for Alirocumab is set at a maximum daily dose of 150 mg, with a total maximum dose of 3750 mg over a treatment period of 15 days. The primary objective of the trial is to evaluate the efficacy of Alirocumab in lowering LDL-cholesterol levels in recent heart transplant recipients, in conjunction with standard lipid-lowering therapy.

In addition to Alirocumab, the study includes a **placebo** product, referred to as the "Placebo product for REGN727." The placebo serves as a comparator treatment to assess the efficacy of Alirocumab. The placebo is not associated with any active pharmaceutical ingredient and is utilized to maintain the study's double-blind design. The placebo administration details, including dosage and route, are not specified, as it is intended to mimic the administration of the experimental drug without exerting any pharmacological effect.

Participants in the trial will also receive standard-of-care therapy with atorvastatin, administered at a dosage of 10 mg daily. This background therapy is intended to provide a consistent lipid-lowering effect across all study participants, allowing for a clearer assessment of Alirocumab's impact on lipid profiles. Compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

The efficacy of **alirocumab** in the clinical trial will be assessed by evaluating its impact on lipid profiles in recent heart transplant recipients. The primary endpoints include the mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), apolipoprotein B (ApoB), lipoprotein a (Lp[a]), and apolipoprotein A1 (ApoA1) at treatment visits 2, 3, 4, 5, and 6. Secondary endpoints involve the percent change from baseline in calculated LDL-C at Treatment visit 6, calculated LDL-cholesterol at every study visit, and differences in other lipids and lipoproteins at each study visit. Additionally, changes in LDL-C and other lipid parameters between Treatment visit 6 and Visit 7 will be analyzed. The trial will also assess the difference in mean intimal thickness change and mean lumen volume change between Treatment visit 6 and Treatment visit 1, using optical coherence tomography (OCT).