Letermovir Use in Heart Transplant Recipients

NCT ID: NCT04904614

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-05
• Study Completion Date: 2025-01-14

Brief Summary

This is an open label trial in which letermovir will be given as prophylaxis for the prevention of cytomegalovirus (CMV) infection and disease to all heart transplants who are at risk for cytomegalovirus. The study will compare a 30 patient prospective cohort to a retrospective cohort of 374 heart transplant recipients for the rates of neutropenia. In addition, the tolerability of letermovir will be assessed in this population.

Detailed Description

This open label trial will follow 30 heart transplant recipients at Tufts Medical Center who will receive letermovir in a dose of 480 mg daily for either 3 or 6 months depending on the CMV risk category, and who will be followed for one year. Comparison will be made to a cohort of heart transplant recipients as historical controls in a recently presented study (Chow, J, et al ISHLT 2021). Standard follow up will be provided as if the patients were receiving valganciclovir prophylaxis. Post prophylaxis T cell immunity to all subjects enrolled will be tested. Clinical outcomes are detailed below.

Conditions

Cytomegalovirus Disease; Cytomegalovirus Infections; Heart Transplant Infection; Antiviral Toxicity; Neutropenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

single arm

Letermovir 480 mg daily for cmv prophylaxis

Group Type: OTHER

Letermovir

Intervention Type: DRUG

Open label trial of the licensed drug, letermovir, in a population of heart transplant recipients for which it is not yet licensed

Interventions

Letermovir

Open label trial of the licensed drug, letermovir, in a population of heart transplant recipients for which it is not yet licensed

Intervention Type: DRUG

Other Intervention Names

Prevymis

Eligibility Criteria

Inclusion Criteria

1. Adults between 18-70 will be eligible for participation

2. Written informed consent and able to participate with follow up

3. Heart transplant recipients who are not Cytomegalovirus (CMV) donor negative and CMV recipient negative (CMV D-/R-)

4. Not enrolled in competing clinical trials

Exclusion Criteria

1. Dual heart and kidney transplant recipients

2. Patients who do not survive 72 hours post transplant

3. HIV infection

4. Patients with creatinine clearance less than 10 ml per min at time of enrollment

5. Hypersensitivity to letermovir

6. On continuous veno-venous hemofiltration or renal dialysis at the time of enrollment

7. Received a previous solid organ transplant or stem cell transplant.

8. Has Child Pugh Class C severe hepatic insufficiency at screening.

9. Has both moderate hepatic insufficiency AND moderate to severe renal insufficiency at screening.

Note: Moderate hepatic insufficiency is defined as Child Pugh Class B; moderate to severe renal insufficiency is defined as Creatine Clearance <50 mL/min, as calculated by the Cockcroft-Gault equation (as above), respectively.

10. Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.

11. Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.

12. Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.

13. 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.

Hemoglobin <8 g/dL Platelets <25,000 cells/µL Absolute neutrophil count <1,000 cells/µL Total bilirubin >2.5 × ULN ALT >5 × ULN AST >5 × ULN

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CMV = cytomegalovirus; IgG = immunoglobulin G; ULN = upper limit of normal

15. Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with an investigational monoclonal antibody will be eligible to participate after a 150-day washout period.

Note: Investigational regimens involving combinations of approved agents are not permitted. Other non-interventional or other observational studies are allowed.

16. Has previously participated in this study or any other study involving letermovir.

17. 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.

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• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Tufts Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.

Reference Type: BACKGROUND

PMID: 29596116 (View on PubMed)

Snydman DR. Epidemiology of infections after solid-organ transplantation. Clin Infect Dis. 2001 Jul 1;33 Suppl 1:S5-8. doi: 10.1086/320897.

Reference Type: BACKGROUND

PMID: 11389515 (View on PubMed)

Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, Haider S, Ullmann AJ, Katayama Y, Brown J, Mullane KM, Boeckh M, Blumberg EA, Einsele H, Snydman DR, Kanda Y, DiNubile MJ, Teal VL, Wan H, Murata Y, Kartsonis NA, Leavitt RY, Badshah C. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017 Dec 21;377(25):2433-2444. doi: 10.1056/NEJMoa1706640. Epub 2017 Dec 6.

Reference Type: BACKGROUND

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Goldner T, Hewlett G, Ettischer N, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol. 2011 Oct;85(20):10884-93. doi: 10.1128/JVI.05265-11. Epub 2011 Jul 13.

Reference Type: BACKGROUND

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Kaul DR, Stoelben S, Cober E, Ojo T, Sandusky E, Lischka P, Zimmermann H, Rubsamen-Schaeff H. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant. 2011 May;11(5):1079-84. doi: 10.1111/j.1600-6143.2011.03530.x.

Reference Type: BACKGROUND

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Marschall M, Stamminger T, Urban A, Wildum S, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother. 2012 Feb;56(2):1135-7. doi: 10.1128/AAC.05908-11. Epub 2011 Nov 21.

Reference Type: BACKGROUND

PMID: 22106211 (View on PubMed)

Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-Schaeff H, Zimmermann H. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010 Mar;54(3):1290-7. doi: 10.1128/AAC.01596-09. Epub 2010 Jan 4.

Reference Type: BACKGROUND

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Giulieri S, Manuel O. QuantiFERON(R)-CMV assay for the assessment of cytomegalovirus cell-mediated immunity. Expert Rev Mol Diagn. 2011 Jan;11(1):17-25. doi: 10.1586/erm.10.109.

Reference Type: BACKGROUND

PMID: 21171917 (View on PubMed)

Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, Pikis A, Razonable RR, Miller V, Griffiths PD; Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87-91. doi: 10.1093/cid/ciw668. Epub 2016 Sep 28.

Reference Type: BACKGROUND

PMID: 27682069 (View on PubMed)

Gardiner BJ, Nierenberg NE, Chow JK, Ruthazer R, Kent DM, Snydman DR. Absolute Lymphocyte Count: A Predictor of Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients. Clin Infect Dis. 2018 Oct 15;67(9):1395-1402. doi: 10.1093/cid/ciy295.

Reference Type: BACKGROUND

PMID: 29635432 (View on PubMed)

Arbo MD, Snydman DR. Influence of blood culture results on antibiotic choice in the treatment of bacteremia. Arch Intern Med. 1994 Dec 12-26;154(23):2641-5. doi: 10.1001/archinte.1994.00420230024004.

Reference Type: BACKGROUND

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George MJ, Snydman DR, Werner BG, Griffith J, Falagas ME, Dougherty NN, Rubin RH. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med. 1997 Aug;103(2):106-13. doi: 10.1016/s0002-9343(97)80021-6.

Reference Type: BACKGROUND

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

00001538

Identifier Type: -

Identifier Source: org_study_id