E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Main purpose is to assess the efficacy and safety of prophylactic use of oral Maribavir versus oral Ganciclovir to prevent cytomegalovirus disease in recipients of orthotopic liver transplants at high risk of developing CMV disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009701 |
E.1.2 | Term | CMV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this study is to compare the efficacy of the prophylactic use of oral maribavir versus oral ganciclovir when administered for up to 14 weeks for the prevention of cytomegalovirus disease in recipients of orthotopic liver transplants at high risk developing CMV disease. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are to compare the safety and tolerability of the prophylactic use of oral maribavir versus oral ganciclovir when administered for up to 14 weeks in recipients of orthotopic liver transplants at high risk developing CMV disease and to evaluate the pharmacokinetics of maribavir in this subject population. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title of the sub-study is the same as the main protocol title. A sub-study to evaluate the pharmacokinetics of maribavir will be conducted at selected investigative sites. Sub-study procedures require the collection of additional blood samples at selected time points. The details of this sub-study are provided in on page 46 and Appendix IX of the protocol. Within the EU no investigational site will participate in this sub-study. |
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E.3 | Principal inclusion criteria |
Subjects must: 1. Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed. 2. Be >/= 18 years of age. 3. Weigh >/= 40 kg. 4. Be undergoing their first orthotopic liver transplantation (the transplanted graft may be a deceased-donor whole organ, a deceased-donor split-liver graft, or live-donor graft). 5. Have negative pre-transplantation CMV serology and receive a liver from a donor with positive pre-transplantation CMV serology (i.e., donor positive / recipient negative [D+ R–]). 6. Have no detectable CMV infection post-transplant. This must be documented by CMV testing of blood using either CMV pp65 antigenemia assay, CMV DNA PCR, or other CMV DNA detection assay from a sample collected post-transplant. Results from either the central laboratory or a local laboratory can be used for qualification. 7. Have the following findings as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification): · Absolute neutrophil count (ANC) ≥500/mm3 [0.5 x 109/L] · Platelet count ≥25,000/mm3 [25 x 109/L] 8. Be randomized such that dosing with study drug can begin within 10 days post-transplant. 9. If female, be either postmenopausal, surgically sterile, or have a negative serum pregnancy test as part of screening laboratory assessments. Women of child bearing potential also must agree to use an acceptable method of birth control (e.g., abstinence, IUD, or barrier method), as determined by the investigator, during the study drug administration period and for 3 months afterward. Hormonal contraceptives should not be used as the sole method of birth control. If male, must agree to use an acceptable method of birth control (e.g., abstinence or barrier method), as determined by the investigator, during the study drug administration period and for 3 months afterward. 10. Be able to swallow tablets and capsules.
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E.4 | Principal exclusion criteria |
Subjects must not: 1. Be undergoing multi-organ transplantation or have undergone prior organ transplantation (except skin, hair, or cornea). 2. Have known human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process or during screening for this study). 3. Have CMV-related organ disease within 6 months prior to the day of enrollment. 4. Be receiving any of the following therapies at the time of enrollment: · ganciclovir · valganciclovir · foscarnet · cidofovir · acyclovir (>25 mg/kg IV per day) · valacyclovir (>3 g p.o. per day) · famciclovir (>1500 mg p.o. per day) NOTE: A subject may have received any of the above listed drugs prior to enrollment. If this is the case, these drugs must be discontinued by the time of enrollment; no minimum “washout” period is required before commencement of dosing with study drugs. 5. Have received cytomegalovirus immune globulin within 30 days prior to the day of enrollment. 6. Have estimated creatinine clearance <10 mL/min or require dialysis at time of enrollment. 7. Have severe vomiting, diarrhea or other severe gastrointestinal illness within 24 hours prior to the time of enrollment that would preclude administration of oral medication. 8. Require mechanical ventilation or vasopressors for hemodynamic support at time of enrollment. 9. Be pregnant (as determined by b-hCG testing prior to initiation of study drug) or breastfeeding. 10. Have received any investigational antiviral agent or investigational immunosuppressant agent within 30 days before the initiation of study drug. 11. Have received maribavir in a previous clinical trial. 12. Have any clinically significant medical or surgical condition (other than the underlying reason for transplantation) that in the investigator’s or sponsor’s opinion would compromise the outcome of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the incidence of CMV disease (either symptomatic CMV infection or CMV organ disease, as adjudicated by an independent Endpoint Committee) within 6 months post-transplant. The incidence of CMV disease also will be evaluated within 100 days and 12 months post-transplant. Analysis populations include: ITT (Intent-to-Treat, all subjects randomized to treatment); ITT-S (Intent-to-Treat—Safety, all ITT subjects who received at least one dose of study medication); and ITT-E (CMV Evaluable, all ITT-S subjects with negative CMV assays at initiation of study drug therapy).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |