E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Main purpose is the assess the efficacy and safety of prophylactic use of Maribavir to prevent cytomegalovirus disease in recipients of allogeneic stem cell transplants. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 objectives of this study are to evaluate the efficacy of the prophylactic use of maribavir administered orally for up to 12 weeks for the prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants and to evaluate the safety and tolerability of the prophylactic use of maribavir administered orally for up to 12 weeks in this subject population. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective of the trial is 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 sub-study is the same as main protocol title. A substudy to evaluate CMV-specific immunity will be conducted at selected investigative sites. Substudy procedures require the collection of additional blood samples at selected time points. The details of this substudy are provided in Appendix X of the protocol. Within EU no investigational sites will participate in this substudy. |
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E.3 | Principal inclusion criteria |
Subjects must: * Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed. * Be at least 18 years of age. * Weigh at least 40 kg. * Have undergone allogeneic bone marrow, peripheral blood stem cell, or cord blood transplantation (transplant may be related or unrelated, T-cell depleted or non-T-cell depleted, myeloablative or non-myeloablative/reduced intensity). * Have positive pre-transplantation CMV serology (recipient seropositive) or receive stem cells from a donor with positive pre-transplantation CMV serology (donor seropositive). I.e.,: Donor positive / Recipient positive (D+ R+), or Donor negative / Recipient positive (D– R+), or Donor positive / Recipient negative (D+ R–) * Have no detectable CMV infection post-transplant (unequivocally negative pp65 antigenemia and plasma CMV DNA PCR assays) from samples collected within 5 days prior to initiation of study drug (results from either the central laboratory or a local laboratory can be used for qualification). * Have transplant engraftment (absolute neutrophil count 500/mm3 [0.5 x 109/L] from 3 consecutive samples taken on separate days). * Be randomized such that dosing with study drug can begin between 14 days and 30 days post-transplant (inclusive). * If female, be either postmenopausal, surgically sterile, or have a negative serum pregnancy test within 5 days prior to initiation of study drug. 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 2 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 2 months afterward. * Be able to swallow tablets.
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E.4 | Principal exclusion criteria |
* Have CMV-related organ disease within 6 months prior to randomization. * Have received any of the following therapies after the day of stem cell transplantation and prior to initiation of study drug: 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) cytomegalovirus immune globulin * Have known human immunodeficiency virus (HIV) infection. * Be receiving therapy with phenytoin at time of enrollment. * Have any of the following findings within 5 days prior to initiation of study drug: Serum AST or ALT > 7 x the upper limit of normal Serum total bilirubin > 3 x the upper limit of normal * Have severe vomiting, diarrhea or other severe gastrointestinal illness within 24 hours prior to the time of randomization that would preclude administration of oral medication (subjects with active gastrointestinal graft-versus-host disease are allowed only if oral medications are permissible and the investigator determines that this condition is stable or improving). * Require mechanical ventilation, vasopressors for hemodynamic support, or dialysis at the time of randomization. * Be pregnant (as determined by -hCG testing prior to initiation of study drug) or breastfeeding. * Have received any investigational antiviral drug within 30 days before the initiation of study drug. * Have received maribavir in a previous clinical trial. * 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 (as adjudicated by the independent Endpoint Committee) within 180 days post-transplant. The incidence of CMV disease also will be evaluated within 100 days and 12 months post-transplant. Key secondary endpoints will include incidence of initiation of preemptive anti-CMV therapy, incidence of graft-versus-host disease, mortality, and CMV disease-free survival. Additional efficacy endpoints will include incidence of CMV infection as assessed by CMV surveillance assays and time of onset of CMV infection or CMV disease. |
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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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |