Efficacy and safety of alirocumab to prevent early cardiac allograft vasculopathy in recent heart transplant recipients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institute For Clinical And Experimental Medicine

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Nov 2019 → 5 May 2025

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

sanofi

External identifiers

EU CT number

2024-514023-42-00

EudraCT number

2019-000078-47

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy of alirocumab/placebo in lowering LDL-cholesterol in recent heart transplant recipients as an adjunct to standard background lipid lowering therapy with atorvastatin 10 mg daily. Furthermore, the impact of alirocumab on other parameters of lipid profile [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a (Lp [a]), triglyceride (TG) levels] will be evaluated. The effect will be assessed in the time period between 1 and 12 months after heart transplantation.

Secondary objectives 4

1. To evaluate safety of alirocumab in comparison to placebo in recent heart transplant recipients.
2. To evaluate changes in coronary artery wall structure by OCT assessed at 1 and 12 months after heart transplantation.
3. To evaluate effect of alirocumab on LDL-C and the other parameters of lipid profile (total cholesterol, HDL-C, ApoA1, ApoB, Lp(a), TG levels) at every visit in comparison to placebo.
4. To evaluate changes of LDL-C and the other parameters of lipid profile in the alirocumab group between Treatment visit 6 (End of Treatment) and Visit 7 (End of Study) to assess lipid level rebound.

Conditions and MedDRA coding

Cardiac allograft vaculopathy in recent heart transplant recipients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. New cardiac transplant recipient ≥ 18 years of age willing to participate in the study.
2. Ability to understand study procedures and to comply with them for the entire length of the study.
3. Written informed consent obtained from subject or subject’s legal representative.
4. Heart transplantation surgery performed 3-8 weeks before the baseline visit.

Exclusion criteria 9

1. Known hypersensitivity/allergy reaction to study medication.
2. Complicated post-transplant outcome with poor neurological status, multiorgan failure or graft dysfunction.
3. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
4. Lipoprotein apheresis is planned or performed.
5. Level of LDL-C ≥ 8 mmol/L at screening.
6. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
7. Participation in any other interventional study.
8. Known hypersensitivity/allergy to contrast agent or severe renal insufficiency (eGFR ˂ 30 ml/min/1.75 m2) exclude patient from OCT imaging only, not the whole study.
9. Women with child-bearing potential will not be excluded from the trial but will be advised to use reliable contraception – which is the standard for post-transplant care.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean level of LDL-C, HDL-C, TC, TG, ApoB, Lp[a], ApoA1 at treatment visit 2, 3, 4, 5 and 6.

Secondary endpoints 6

1. Percent change from baseline in calculated LDL-C at Treatment visit 6
2. Calculated LDL-cholesterol at every study visit (Treatment visit 1, 2, 3, 4, 5, and Visit 6)
3. Difference in other lipids and lipoproteins (TC, HDL-C, ApoB, ApoA1, Lp(a), TG) at every study visit (Treatment visit 1, 2, 3, 4, 5, and Visit 6)
4. Change of LDL-C and the other parameters of lipid profile (TC, HDL-C, ApoB, ApoA1, Lp(a), TG) between Treatment visit 6 and Visit 7
5. Difference in mean of intimal thickness change (between Treatment visit 6 – Treatment visit 1) assessed by OCT
6. Difference in mean lumen volume change (between Treatment visit 6 – Treatment visit 1) assessed by OCT.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institute For Clinical And Experimental Medicine

Sponsor organisation

Institute For Clinical And Experimental Medicine

Address

Videnska 1958/9 Krc

City

Prague

Postcode

140 00

Country

Czechia

Scientific contact point

Organisation

Institute For Clinical And Experimental Medicine

Contact name

Vojtěch Melenovský

Public contact point

Organisation

Institute For Clinical And Experimental Medicine

Contact name

Vojtěch Melenovský

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications