Cytomegalovirus Prophylaxis with Letermovir in Heart Transplant Recipients: A Non-randomized Cohort Pilot Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Ljubljana

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Virus Diseases [C02]

Trial duration

17 Sep 2024 → 1 May 2026

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MSD

External identifiers

EU CT number

2024-517354-98-00

EudraCT number

2022-001514-18

ClinicalTrials.gov

NCT05432778

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective of the study is to investigate the efficacy of letermovir-based CMV prophylaxis in patients after heart transplantation.

Secondary objectives 2

1. to investigate the tolerability of letermovir-based CMV prophylaxis in patients after heart transplantation
2. to explore the potential correlation between letermovir-based CMV prophylaxis and restitution of cell-regulated immunity in patients after heart transplantation.

Conditions and MedDRA coding

CMV infection in heart transplant recipients

Regulatory references

Plan to share IPD

No

IPD plan description

/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. •heart transplant recipient (new)
2. •moderate (D+/R+ and D-/R+) or high (D+/R-) risk CMV serostatus
3. •signed informed consent for participation in the study
4. • age ≥ 18 years
5. •not enrolled in competing clinical trials

Exclusion criteria 27

1. •short-term mechanical circulatory support prior HTX
2. •multi-organ transplantation
3. •ongoing CMV infection/disease
4. •D-/R- CMV serostatus
5. •heart re-transplantation
6. •need for intensified immunosuppression protocol (>20% cytolytic alloantibodies prior transplant or perioperative (within 7 days after HTX) allograft rejection > 1R)
7. •immunoinduction with ATG
8. •pregnancy
9. •active participation in another interventional clinical trial
10. •known hypersensitivity to letermovir
11. •known hypersensitivity to valgancyclovir
12. •known hematological disorders (apart from anemia)
13. •history of malignancy (< 5 years; except adequately treated basal or squamous cell skin cancer or in situ cervical cancer) or under evaluation for active or suspected malignancy
14. •advanced kindey disease (CrCL < 10 ml/min) at enrollment
15. •advanced liver disease (Child Pugh Class C)
16. •combined moderate kidney (CrCL < 50 ml/min) and liver (Child Pugh Class B) insufficiency at screening
17. •concomitant administration with pimozide
18. •concomitant administration with ergot alkaloids
19. •concomitant administration with St. John’s wort (Hypericum perforatum)
20. •concomitant administration of cyclosporine
21. •concomitant use of dabigatran, atorvastatin, simvastatin, rosuvastatin or pitavastatin is contraindicated
22. •known hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
23. •combined hepatic and renal impairment
24. •HIV infection
25. •Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or put the participant at undue risk, as judged by the investigator, such that it is not in the best interest of the participant to participate in this study
26. •Has previously participated in this study or any other study involving letermovir.
27. •Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The rate of early CMV infections/disease during virostatic prophylaxis.

Secondary endpoints 5

1. •The rate of leukopenia during virostatic prophylaxis
2. •The rate of neutropenia during virostatic prophylaxis
3. •The rate of late CMV infections/disease between virostatic discontinuation and 6 months thereafter.
4. •The time-course of the restitution of cell-mediated immunity during virostatic prophylaxis
5. •The rate of CMV resistance to virostatic therapy.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Ljubljana

Sponsor organisation

University Medical Center Ljubljana

Address

Zaloska Cesta 7

City

Ljubljana

Postcode

1000

Country

Slovenia

Scientific contact point

Organisation

University Medical Center Ljubljana

Contact name

Bojan Vrtovec

Public contact point

Organisation

University Medical Center Ljubljana

Contact name

Gregor Poglajen

Sponsor responsibilities

Contact point sponsor

University Medical Center Ljubljana

Article 77 implementation

University Medical Center Ljubljana

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

Documents 5 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