Letermovir Use in Heart Transplant Recipients

NCT04904614 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 00001538
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

cytomegalovirus, letermovir, heart transplantation

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With Neutropenia Compared to Historical Controls

  We will count the number of patients with neutropenia seen over one year and calculate the proportion who become neutropenic. A comparison group of historic controls from a similar population is available for comparison. We know the control group has a 30% likelihood of becoming neutropenic at one year.

  12 months

Secondary Outcomes (5)

• Rate of CMV Infection in Letermovir Recipients Compared to Historical Controls

  1 year

• Rate of Opportunistic Infections in Letermovir Arm Compared to Historical Controls

  1 year

• Tolerability and Compliance of Letermovir

  1 year

• Use of Granulocyte Colony Stimulation Factor (GCSF) in Letermovir Recipients Compared to Historical Controls

  1 year

• Measure of CMV Specific T Cell Immunity in Letermovir Recipients

  single time point measured within 2 weeks after completion of prophylaxis therapy, at either 3 months or 6 months, depending on duration of prophylaxis

Study Arms (1)

single arm

OTHER

Letermovir 480 mg daily for cmv prophylaxis

Drug: Letermovir

Interventions

Letermovir DRUG

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

Also known as: Prevymis

single arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults between 18-70 will be eligible for participation
• Written informed consent and able to participate with follow up
• Heart transplant recipients who are not Cytomegalovirus (CMV) donor negative and CMV recipient negative (CMV D-/R-)
• Not enrolled in competing clinical trials

You may not qualify if:

• Dual heart and kidney transplant recipients
• Patients who do not survive 72 hours post transplant
• HIV infection
• Patients with creatinine clearance less than 10 ml per min at time of enrollment
• Hypersensitivity to letermovir
• On continuous veno-venous hemofiltration or renal dialysis at the time of enrollment
• Received a previous solid organ transplant or stem cell transplant.
• Has Child Pugh Class C severe hepatic insufficiency at screening.
• 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.
• 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.
• 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.
• Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
• 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

Sponsors & Collaborators

• Tufts Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (12)

• 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.

  PMID: 29596116 BACKGROUND

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

  PMID: 11389515 BACKGROUND

• 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.

  PMID: 29211658 BACKGROUND

• 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.

  PMID: 21752907 BACKGROUND

• 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.

  PMID: 21521474 BACKGROUND

• 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.

  PMID: 22106211 BACKGROUND

• 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.

  PMID: 20047911 BACKGROUND

• 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.

  PMID: 21171917 BACKGROUND

• 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.

  PMID: 27682069 BACKGROUND

• 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.

  PMID: 29635432 BACKGROUND

• 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.

  PMID: 7993147 BACKGROUND

• 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.

  PMID: 9274893 BACKGROUND

MeSH Terms

Conditions

Cytomegalovirus Infections; Neutropenia

Interventions

letermovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Results Point of Contact

• Title: Dr. Jennifer Chow
• Organization: Tufts Medical Center

jennifer.chow@tuftsmedicine.org

617-636-5244

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label trial

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 27, 2021
• Study Start: January 5, 2022
• Primary Completion: January 14, 2025
• Study Completion: January 14, 2025
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)