Open Label Trial of Oral Letermovir for CMV Prophylaxis in Thoracic Transplant Recipients

NCT06066957 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 853851
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are:

1. 1.Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients
2. 2.Letermovir will be better tolerated than valganciclovir for CMV prophylaxis in heart and lung transplant recipients, with a higher proportion of days of completed therapy with correct dosing during the planned prophylaxis period
3. 3.Letermovir will have a lower rate of neutropenia than valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
4. 4.Incorrect renal dosing will occur less frequently with letermovir than with valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients

Conditions

Cytomegalovirus Infections; Transplant-Related Disorder

Keywords

CMV; Thoracic Transplant

Outcome Measures

Primary Outcomes (2)

• CMV viral load

  The primary outcome will be CMV infection (CMV viremia with CMV viral load \>1,000, CMV syndrome, or tissue invasive CMV disease) during the planned prophylaxis period and the following 180 days

  Prophylaxis period plus 180 days

• Proportion of days during which appropriately renally-dosed prophylaxis

  The primary outcome will be the proportion of days during which appropriately-dosed prophylaxis was received during the planned treatment course.

  90 to 365 days post intervention

Secondary Outcomes (6)

• Biopsy-proven acute cellular rejection

  Prophylaxis period plus 180 days

• Proportion of subjects who develop CMV resistance

  Prophylaxis period plus 180 days

• Proportion of subjects who develop neutropenia

  90 to 365 days of prophylaxis period

• Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)

  90 to 365 days of prophylaxis period

• Proportion of subjects with Unplanned discontinuation of MMF or azathioprine

  90 to 365 days of prophylaxis period

Study Arms (1)

Letermovir

EXPERIMENTAL

Will include those participants who receive letermovir for CMV prophylaxis as provided through the clinical trial. The "exposed" group will be ascertained prospectively over a one-year period (the "post-intervention" period).

Drug: Letermovir 480 MG [Prevymis]

Interventions

Letermovir 480 MG [Prevymis] DRUG

Letermovir for CMV prophylaxis in thoracic organ transplant recipients. Letermovir will be administered by oral administration, as per study protocol. The intended duration of therapy will be up to 365 days, depending on organ transplanted and donor and recipient CMV status. However, treatment may discontinued as discussed in Section 7. Letermovir is dosed at 480mg daily for patients with CrCl \>10. Dose adjustment, as per package insert, is recommended in setting of co-administration of cyclosporine, with dose reduction of letermovir to 240mg daily. Missed doses of letermovir will not be made up.

Letermovir

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Age is \>=18 years on the day of transplantation.
• Heart or Lung transplant recipient.
• Donor and/or Recipient CMV seropositive (defined by positive IgG) within 1 year prior to transplantation.
• Able to start oral CMV prophylaxis within 14 days (heart graft recipients) or 28 days (lung graft recipients) of transplantation.
• Males at birth agree to use contraception during the treatment period, and for at least 90 days after the last dose of study treatment, and refrain from donating sperm during this period.
• Female at birth is not pregnant or breastfeeding. If of childbearing potential, agrees to follow the contraception guidance during the treatment period and for at least 90 days after the last dose of study treatment.
• A male or female subject who is of reproductive potential agrees to true abstinence or to use (or have their partner use) 1 acceptable method of birth control starting from the time of consent through 90 days after the last dose of study therapy. True abstinence is defined as abstinence in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, and vasectomy OR use of appropriate double barrier contraception as per local regulations or guidelines. Hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables) are unacceptable methods of birth control for use in this study because it is not known whether these methods are affected by co- administration of letermovir.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Any prior solid organ transplant.
• Dual organ transplantation.
• Prior treated CMV infection.
• Unknown CMV serostatus of the donor or recipient.
• Suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations and/or acyclovir formulations.
• CrCl \<10 mL/minute, using Cockcroft-Gault equation, or renal replacement therapy at the time of enrollment.
• Child-Pugh Class C severe hepatic insufficiency at enrollment.
• Both moderate hepatic insufficiency AND moderate renal insufficiency. Note: Moderate hepatic insufficiency is defined as Child Pugh Class B; moderate renal insufficiency is defined as a creatinine clearance less than 50 mL/min, as calculated by the Cockcroft-Gault equation.
• Neutropenia, defined as absolute neutrophil count \<1,500/microliter, at the time of enrollment.
• Severe thrombocytopenia, defined as platelets \<50,000/microliter, at the time of enrollment.
• Any uncontrolled infection on the day of enrollment.
• Documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to enrollment, or hepatitis B surface antigen (HBsAg) within 90 days prior to enrollment.
• Documented positive result for hepatitis C virus antibody (HCV-Ab) and with detectable HCV ribonucleic acid (RNA) within 90 days prior to enrollment with need for treatment with direct acting antiviral other than the following: glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, or elbasvir/grazoprevir.
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Penn Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

letermovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Central Study Contacts

Kathryn Whitaker, MD

CONTACT

267-581-2135; Kathryn.Whitaker@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a prospective cohort design. Subjects exposed to letermovir for CMV prophylaxis following heart or lung transplantation will be compared with those who received standard valganciclovir prophylaxis in the two years before the study began (referred to as the "pre-intervention" period). The goal is to evaluate the efficacy and tolerability of letermovir.

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: October 4, 2023
• Study Start: April 4, 2024
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: May 21, 2025

Record last verified: 2025-05

Locations

US (1)