Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients

Study Overview
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Brief Summary
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This is a research study to test the tolerability and clinical effectiveness of the study drug, Letermovir (LET), when used as secondary prophylaxis following treatment of Cytomegalovirus (CMV) infection and disease in a solid organ transplant recipient. This study is an open label trial in which Letermovir will be prescribed to prevent the recurrence of CMV infection and disease in a solid organ transplant recipient following treatment of CMV infection or disease.

Detailed Description
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This study will enroll solid organ transplant recipients who develop cytomegalovirus infection and disease who have been treated. At the time of finishing treatment, if the clinician feels that secondary prophylaxis is indicated, they will be enrolled to receive Letermovir 480 mg orally once a day for 60 days. CMV specific T cell assays will be obtained at the initiation of secondary prophylaxis and at the discontinuation of secondary prophylaxis. Patients will be followed for 4 months following discontinuation of secondary prophylaxis to see if they relapse.

Official Title
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A Pilot Trial of the Tolerability and Clinical Effectiveness of Letermovir When Used for Secondary Prophylaxis to Prevent Recurrent Cytomegalovirus Disease in Solid Organ Transplant Recipients

Conditions
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Cytomegalovirus Infections, Infection in Solid Organ Transplant Recipients, Neutropenia, Antiviral Toxicity

Intervention / Treatment
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* Drug: Letermovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (> 18 years old) solid organ transplant recipients (heart, kidney or liver patients) recovering from treated CMV disease in whom the clinician deems that the patient need secondary prophylaxis and in whom written informed consent is obtained. Patient able to participate with follow up for 6 months Not enrolled in competing clinical trials Exclusion Criteria: Patients with creatinine clearance less than 10 ml per min at time of enrollment Hypersensitivity to letermovir or has a CMV isolate which is known to be resistant to letermovir based on prior testing On CVVH or renal dialysis at the time of enrollment 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 (Appendix 8); moderate to severe renal insufficiency is defined as CrCl <50 mL/min, as calculated by the Cockcroft-Gault equation. 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. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the 6 months) of drug or alcohol abuse or dependence. Note: Participants with a history of marijuana use which is not deemed excessive by an investigator or does not interfere with the participant's daily function may participate in the study. 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. Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent that is not approved or is planning to participate in a study of a CMV vaccine or another unapproved CMV investigational agent during the course of this study. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Open label trial of letermovir given to eligible patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: single arm<br>This is an open label single arm study | Drug: Letermovir<br>* Open label 480 mg given daily for 60 days<br>* Other names: Active drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Relapse after prophylaxis | Proportion of patients with relapsing CMV disease up to 6 months after starting drug | 6 months after starting intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opportunistic infection | Rate of opportunistic infections or other infectious outcomes in the letermovir arm. | 6 months after starting | 
| Adverse events associated with taking letermovir | Tolerability and compliance of patients taking letermovir in terms of adverse events | 6 months after starting | 
| Neutropenia | Duration and nadir of neutropenia in the letermovir group | 6 months after starting intervention | 
| Rejection | Rate of rejection at 6 months after starting secondary prophylaxis in the letermovir arm. | 6 months | 
| T cell function | Proportion of patients who have demonstrated CMV specific T cell immunity at start of letermovir secondary prophylaxis will be compared to the proportion who have CMV specific T cell function at the discontinuation of prophylaxis | 6 months after starting intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell immunity, Cytomegalovirus infection, Letermovir, Secondary prophylaxis, neutropenia