Efficacy and Safety of Maribavir in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment

Overview

About this study

The purpose of this study is to determine if an investigational treatment (Maribavir) is safe and effective in treating transplant recipient patients with cytomegalovirus (CMV) infections that are refractory or resistant to treatment.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. 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. Be a recipient of hematopoietic stem cell or solid organ transplant.
  3. Have a documented CMV infection 910 ≥IU/ml in blood or plasma samples, from two consecutive assessments separated by at least one day, taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization.
  4. Have a current CMV infection refractory or resistant to current treatment. Refractory is defined as failure to have >1log10 decrease in CMV viral load within minimum of 2 weeks of treatment with ganciclovir, valganciclovir, foscarnet or cidofovir .
  5. Per Investigator's judgment, be eligible for treatment with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir).
  6. Weight ≥35 kg.
  7. 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):
    1. Absolute neutrophil count (ANC) ≥1000/mm3 [1.0 x 109/L]
    2. Platelet count ≥25,000/mm^3 [25 x 10^9/L],
    3. Hemoglobin ≥8g/dL.
    4. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73m^2 as assessed by Modification of Diet in Renal Disease (MDRD) formula for subjects ≥18 years of age or Schwartz formula for subjects <18 years of age.
  8. All females of child bearing potential must have a negative pregnancy test at screening. 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.
  9. Be able to swallow tablets, or receive crushed tablets via a nasogastric or orogastric tube.
  10. Be willing and have an understanding and ability to fully comply with study procedures and restrictions defined in the protocol.
  11. Be willing to provide necessary samples (eg, biopsy) for the diagnosis of tissue invasive CMV disease at Baseline as determined by the Investigator.
  12. 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. Requires ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated NOTE: A subject who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study must discontinue their use before the first dose of study drug. If subject is currently receiving cidofovir and is assigned another anti-CMV agent 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, or artesunate when study treatment is initiated. NOTE: Subjects who may be receiving leflunomide 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.
  7. 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 CMV hepatitis will not be excluded despite having >5 times ULN at screening.
  8. Have positive results for human immunodeficiency virus (HIV). Subjects must have a confirmed negative result within 3 months of study entry or be willing to be tested at Screening
  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 anti-CMV vaccine at any time.
  13. Have active malignancy with the exception of nonmelanoma skin cancer. Subjects who have had a HSCT and who experience relapse or progression of the malignancy as per investigator's opinion are not to be enrolled.
  14. Undergoing treatment for acute or chronic hepatitis C.
  15. 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Raymund Razonable, M.D.

Closed for enrollment

Contact information:

Maria Stevens

(507)422-5992

Stevens.Maria@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20318549

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