A Study of the Safety and Efficiency of Experimental Drug Maribavir in Transplant Recipients With Cytomegalovirus (CMV) Infection

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 12 years or older
Gender:
Any
Healthy Volunteers: No
Keywords: Cytomegalovirus (CMV), Cytomegalovirus, CMV, viral infection, infectious disease, transplant, post-transplant infection
Type: Drug study, Phase 3
Target:
5 Participants
Investigator:
Description
We invite you to take part in this research study because:
- you have a viral infection, cytomegalovirus (CMV)
- you have also received a solid organ transplant (SOT) or
- you have received a hematopoietic stem cell transplant.

A hematopoietic stem cell is an immature cell that can develop into all types of blood cells.

The current antiviral treatment you are receiving is not improving the infection. The infection may have also become resistant to the current treatment.

This research study will look at the safety and effectiveness of the experimental drug, maribavir. It will be compared to current anti-CMV therapy used to manage CMV infections. Maribavir has not yet been approved by the FDA.

CMV is a common infection. In the US about 50-80% of the population has been infected with CMV by 40 years of age. CMV infection usually has no symptoms or only mild symptoms in healthy adults.

However, serious disease occurs in individuals who are immunocompromised (weakened immune system). For example, patients that have received transplants.

There is currently no cure or vaccine for CMV. This study will help determine whether an experimental drug, maribavir, is a safe and effective treatment for transplant recipients. We hope to learn if there are any unwanted effects on your health related to the use of experimental maribavir.

In this study, you will be randomly assigned to either marivabir, the Study Drug, or current FDA approved drugs used to treat CMV infections: ganciclovir, valganciclovir, foscarnet, and cidofovir.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  1. The subject must be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the subject before completing any study-related procedures.
  2. The subject must be a recipient of hematopoietic stem cell or solid organ transplant.
  3. The subject must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central speciality laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
  4. The subject must have a current CMV infection refractory or resistant to treatment. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after 2 or more weeks of continuous treatment with intravenous (IV) ganciclovir, oral valganciclovir, IV foscarnet, or IV cidofovir. This definition applies to the current CMV infection and the most recently administered anti-CMV agent. Resistant is defined as documented failure to achieve > 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after 2 or more weeks of continuous treatment with IV ganciclovir, oral valganciclovir, IV foscarnet, or IV cidofovir. This definition applies to the current CMV infection and the most recently administered anti-CMV agent. AND Documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir, valganciclovir, foscarnet, or cidofovir.
  5. The Investigator must be willing to treat the subject with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
  6. The subject must be >= 12 years of age at the time of consent
  7. The subject must weigh >= 35 kilogram (kg).
  8. The subject must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
  9. Absolute neutrophil count (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 109^9/liter [L])
  10. Platelet count >= 25,000/mm^3 [25 x 10^9/L],
  11. Hemoglobin >= 8 gram per deciliter (g/dL).
  12. Estimated glomerular filtration rate (eGFR) > 30 (milliliter per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for subjects >= 18 years of age or Schwartz formula for subjects less than (<) 18 years of age.
  13. The subject must have a negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening, if a female of child bearing potential. Additional urine pregnancy tests may be done per institutional requirements. Sexually active females of child bearing potential must agree to comply with any applicable contraceptive requirements of the protocol. If male, must agree to use an acceptable method of birth control, as defined in the protocol, during the study treatment administration period and for 90 days afterward if treated with maribavir, ganciclovir, valganciclovir, or cidofovir and for 180 days afterward if treated with foscarnet.
  14. The subject must be able to swallow tablets, or receive tablets crushed and/or dispensed in water via nasogastric or orogastric tube.
  15. The subject must be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
  16. The subject must be willing to provide necessary samples (example [e.g,] biopsy) for the diagnosis of tissue invasive CMV disease at baseline as determined by the Investigator.
  17. The subject must have a life expectancy of >= 8 weeks.

Exclusion criteria:

  1. Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.
  2. Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A subject who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If subject is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the subject must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment.
  3. Be receiving leflunomide, letermovir, or artesunate when study treatment is initiated. NOTE: Subjects who may be receiving leflunomide or letermovir must discontinue the use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study treatment. Subjects receiving artesunate must discontinue the use prior to the first dose of study treatment.
  4. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study treatment that would preclude administration of oral/enteral medication.
  5. Have known hypersensitivity to the active substance or to an excipient for a study treatment.
  6. Have tissue invasive CMV disease with central nervous system involvement including the retina (example, CMV retinitis).
  7. Have serum aspartate aminotransferase (AST) > 5 times upper limit of normal (ULN) at screening, or serum alanine aminotransferase (ALT) > 5 times ULN at screening, or total bilirubin >= 3.0 x ULN at screening (except for documented Gilbert's syndrome), by local or central lab. Subjects with biopsy confirmed CMV hepatitis will not be excluded from study participation despite AST or ALT > 5 times ULN at screening.
  8. Have known (previously documented) positive results for human immunodeficiency virus (HIV).
  9. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
  10. Be female and pregnant or breast feeding.
  11. Have previously received maribavir.
  12. Have received any investigational agent with known anti-CMV activity within 30 days before initiation of study treatment or investigational CMV vaccine at any time.
  13. Have received any unapproved agent or device within 30 days before initiation of study treatment.
  14. Have active malignancy with the exception of nonmelanoma skin cancer. Subjects who have had a hematopoietic stem cell transplant (HSCT) and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.
  15. Be undergoing treatment for acute or chronic hepatitis C.
  16. Have any clinically significant medical or surgical condition that, in the investigator's opinion, could interfere with the interpretation of study results, contraindicate the administration of the assigned study treatment, or compromise the safety or well-being of the subject.
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
We expect that you will be in this research study for about 22 weeks. Some patients may be in the study up to 29 weeks.
Recruitment period
From March 20, 2018
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817
Contact
Kate Trigg
Research Topic
Conditions:
  • Cytomegalovirus (CMV)