A Phase 3 Study of Brincidofovir Versus Valganciclovir for the Prevention of Cytomegalovirus
Condition: Cytomegalovirus Disease; Kidney Transplant Infection
MeSH terms: Cytomegalovirus Infections
Intervention: Brincidofovir; Valganciclovir
Intervention MeSH terms: Valganciclovir; Brincidofovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cytomegalovirus; CMV

Summary:

      This was a randomized, double-blind, double-dummy, parallel-group, multicenter study of the
      efficacy, safety, and tolerability of oral brincidofovir (BCV) versus valganciclovir for the
      prevention of cytomegalovirus (CMV) disease in CMV-seropositive kidney transplant recipients
      who received antilymphocyte induction therapy.
    

Eligibility criteria:

        Inclusion Criteria

        Subjects must have met all of the following criteria, as applicable, to be eligible to
        participate in this study:

          1. Were male or female kidney transplant recipients who were ≥18 years of age (subject to
             local law/practice for clinical trial participation) and ≤14 days following their
             first or second renal allograft.

          2. Were at high risk of cytomegalovirus (CMV) infection, which for the purposes of this
             study, was defined as CMV-seropositive recipients who received lymphocyte depleting
             induction treatment with antithymocyte globulin (Thymoglobulin® or Atgam®) prior to or
             during the qualifying transplant.

          3. Had an estimated glomerular filtration rate of >10 mL/min (Cockcroft-Gault equation)
             at screening based on local laboratory results.

          4. Were CMV viremia negative (i.e., "not detected") as measured by the designated central
             virology laboratory using the Roche COBAS® AmpliPrep/COBAS® TaqMan® CMV Test no more
             than 5 days prior to subject randomization, and at all prior assessments performed
             since transplant under local standard of care.

          5. Were able to ingest, absorb, and tolerate tablets.

          6. If male, was willing to use an acceptable contraceptive method(s) throughout the
             duration of his participation in the study, i.e., through Week 24.

          7. If female of childbearing potential, i.e., not postmenopausal or surgically sterile,
             was willing to use 2 acceptable contraceptive methods, 1 of which must have been a
             barrier method, throughout the duration of her participation in the study, i.e.,
             through Week 24.

          8. Were willing and able to provide informed consent.

          9. Were willing and able to participate in all required study activities for the entire
             duration of the study (i.e., through Week 24).

        Exclusion Criteria

        Subjects who met any of the following criteria were not eligible to participate in this
        study:

          1. Weighed ≤50 kg (110 lbs) or ≥120 kg (265 lbs).

          2. Were pregnant or breastfeeding or intended to conceive during the study period (i.e.,
             through Week 24).

          3. Received a stem cell transplant or solid organ transplant other than a kidney
             transplant.

          4. Had suspected CMV disease (either syndrome or tissue-invasive disease) or detectable
             CMV viremia by the central virology laboratory prior to the first dose of study drug.

          5. Had a history of CMV disease (either syndrome or tissue-invasive disease) within 6
             months prior to the first dose of study drug.

          6. Had an absolute neutrophil count of < 500 cells/μL, platelet count of < 25,000
             platelets/μL, or hemoglobin of < 8 g/dL at screening.

          7. Had hypersensitivity (not including renal dysfunction or an eye disorder) to
             valganciclovir (vGCV), ganciclovir (GCV), cidofovir (CDV), or brincidofovir (BCV) or
             their excipients.

          8. Had received (or who are anticipated to need treatment with) any of the following:

               -  GCV, vGCV, foscarnet, intravenous CDV, or any other anti-CMV therapy (including
                  CMV immune globulin, cell-based therapies, and investigational anti-CMV drugs,
                  e.g., leflunomide, letermovir [previously AIC246], or maribavir) at any time
                  posttransplant;

               -  Any anti-CMV vaccine at any time;

               -  Any other investigational drug within 14 days prior to the first dose of study
                  drug (unless prior approval had been received from the Chimerix Medical Monitor
                  or designee); or

               -  Prior treatment with BCV at any time. [Note: An "investigational drug" was
                  defined as any drug that was not approved for any indication by the FDA (or
                  appropriate regulatory authority).]

          9. Received acyclovir (ACV) orally at >2000 mg total daily dose (TDD) or intravenously at
             >15 mg/kg TDD, valacyclovir (vACV) at > 3000 mg TDD on the first dose of study drug or
             were anticipated to receive any of these drugs at the doses described after the first
             dose of study drug.

         10. Were infected with HIV, hepatitis B virus (HBV), and/or hepatitis C virus (HCV), had
             evidence of active viral replication within 6 months prior to screening, as
             demonstrated by detectable HIV or HCV RNA, or detectable HBV DNA in blood, plasma or
             serum.

         11. Had severe vomiting, diarrhea or malabsorption syndrome on or prior to the first dose
             of study drug.

         12. Had gastrointestinal (GI) disease that would have, in the judgment of the
             investigator, precluded the subject from taking or absorbing oral medication (e.g.,
             gastroparesis, diabetic autonomic neuropathy affecting the GI tract, clinically active
             Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, small bowel
             resection, ileus, or any condition expected to require abdominal surgery during the
             course of study participation).

         13. Had serum alanine aminotransferase or aspartate aminotransferase concentrations >5 x
             the upper limit of normal (ULN).

         14. Had total serum bilirubin >2 x the ULN and direct bilirubin >1.5 x the ULN.

         15. Had moderate (Class B) to severe (Class C) hepatic dysfunction according to the
             Child-Pugh Turcotte scoring system.

         16. Received or would require digoxin or ketoconazole therapy (other than topical
             formulations) during the treatment phase of the study.

         17. Had active malignancies (with the exception of basal cell carcinoma).

         18. Had a serious psychiatric, medical disorder, including abnormal laboratory values,
             that would have, in the judgment of the investigator, put the subject at increased
             risk by participating in the study, or would have interfered with the conduct of
             study.