Open Label Trial of Oral Letermovir for CMV Prophylaxis in Thoracic Transplant Recipients
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Pennsylvania
About this trial
Open label study to determine tolerability and efficacy of letermovir for CMV prophylaxis in heart and lung transplant recipients. The study hypotheses are:
1. Letermovir prophylaxis will be associated with similar rates of CMV infection as valganciclovir among heart and lung transplant recipients 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. Letermovir will have a lower rate of neutropenia than valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients 4. Incorrect renal dosing will occur less frequently with letermovir than with valganciclovir when used for CMV prophylaxis in heart and lung transplant recipients
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Any prior solid organ transplant.
Dual organ transplantation.
Prior treated CMV infection.
Unknown CMV serostatus of the donor or recipient.
Trial design
Design model
Single group
Treatments tested in this trial
Letermovir 480 MG [Prevymis]
DrugLetermovir 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.
Treatment groups
80 Participants
are divided into 1 treatment groupGroup A: LetermovirExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
Prophylaxis period plus 180 days2
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.
Time frame
90 to 365 days post interventionSecondary outcomes
1
Biopsy-proven acute cellular rejection
The proportion of subjects who develop biopsy-proven acute cellular rejection
Time frame
Prophylaxis period plus 180 days2
Proportion of subjects who develop CMV resistance
CMV resistance will be determined by the presence of a clinically significant mutation on genomic sequencing
Time frame
Prophylaxis period plus 180 days3
Proportion of subjects who develop neutropenia
Proportion of subjects who develop Neutropenia (absolute neutrophil count (ANC) less than 1,500/microliter)
Time frame
90 to 365 days of prophylaxis period4
Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)
Proportion of subjects who develop severe thrombocytopenia (platelet count less than 50,000/microliter)
Time frame
90 to 365 days of prophylaxis periodSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Pennsylvania
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Source ClinicalTrials.gov