A Study of the Safety and Efficacy of CMX001 for the Prevention of CMV Infection in CMV-seropositive HCT Recipients
Condition: CMV
MeSH terms: Infections
Intervention: Brincidofovir; Placebo
Intervention MeSH terms: Cidofovir; Brincidofovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CMV; Hematopoietic Stem Cell Transplant Recipients; Prevention

Summary:

      This randomized, double-blind, placebo-controlled, parallel group, multicenter study compared
      the effectiveness of oral brincidofovir (BCV) to placebo for the prevention of
      cytomegalovirus (CMV) infection in stem cell transplant patients who were CMV seropositive
      but negative for CMV viremia before starting treatment with BCV.
    

Eligibility criteria:

        Inclusion Criteria

        Subjects were required to meet all of the following criteria, as applicable, to be eligible
        to participate in this study:

          1. Were allogeneic hematopoietic stem cell transplant (HCT) recipients who had prior
             evidence of cytomegalovirus (CMV) exposure (CMV-seropositive) before transplantation
             and were CMV viremia negative at screening and at any other assessments performed
             prior to the first dose of study drug.

          2. Were aged ≥18 years.

          3. If male, were willing to use an acceptable contraceptive method(s) throughout the
             duration of his participation in the study, i.e., through Week 24, when engaging in
             sexual intercourse with a female subject of childbearing potential.

          4. If female of childbearing potential, i.e., not postmenopausal or surgically sterile,
             were 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, when engaging in sexual intercourse with a nonsterile male partner.

          5. Were able to begin study drug dosing within 28 days following the qualifying HCT.

          6. Were able to comfortably ingest and absorb oral medication (in the judgment of the
             investigator and base don lack of significant gastrointestinal events/medical
             history).

          7. Were willing and able to understand and provide written informed consent.

          8. 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, as applicable, were not eligible to
        participate in this study:

          1. Was pregnant or planned to become pregnant during the anticipated duration of her
             participation in the study (i.e., through Week 24), or was nursing a child.

          2. Had a positive CMV viremia test (at the designated central virology laboratory or a
             local virology laboratory) at any time between transplant and the first dose of study
             drug.

          3. Weighed ≥120 kg (~265 lbs).

          4. Had hypersensitivity (not renal dysfunction or eye disorder) to cidofovir (CDV),
             brincidofovir (BCV), or its excipients.

          5. Had received (or were anticipated to need treatment with) any of the following:

               -  Ganciclovir, valganciclovir, 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, or maribavir) at any time
                  post-transplant;

               -  Any anti-CMV vaccine at any time;

               -  Any other investigation 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.

          6. Were receiving of the following drugs 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:

               -  Acyclovir orally at >2000 mg total daily dose (TDD) or intravenously at >15 mg/kg
                  TDD;

               -  Valaciclovir at >3000 mg TDD; or

               -  Leflunomide at any dose.

          7. Were receiving digoxin or ketoconazole (other than topical formulations) at the first
             dose of study drug or were anticipated to need treatment with either digoxin or
             ketoconazole during the treatment phase (through Week 14).

          8. Had possible, probably, or definitive CMV disease diagnosed within 6 months prior to
             first dose of study drug.

          9. Were infected with HIV (based on serology), or had an active hepatitis C virus (HCV)
             or hepatitis B virus (HBV) infection, as evidence by detectable plasma HCV RNA or HBV
             DNA, respectively.

         10. Had received another allogeneic HCT (i.e., other than the qualifying HCT) within 2
             years prior to the first dose of study drug.

         11. Had renal insufficiency, as evidence by an estimated glomerular filtration rate (eGFR)
             <15 mL/min or required renal dialysis.

         12. Had hepatic abnormalities as evidence by a screening of alanine aminotransferase or
             aspartate aminotransferase >5 x the upper limit of normal (ULN), as reported by the
             central safety laboratory.

         13. Had a screening total bilirubin >2 x the ULN and direct bilirubin >1.5 x the ULN, as
             reported by the central safety laboratory.

         14. Had active solid tumor malignancies with the exception of basal cell carcinoma or the
             underlying condition necessitating HCT (e.g., lymphomas).

         15. Had Stage 2 or higher graft versus host disease of the gut or any other GI disease
             that would have, in the judgment of the investigator, precluded the subject from
             taking or absorbing oral medication (e.g., 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).

         16. Had any other condition, including abnormal laboratory values, that would have, in the
             judgement of the investigator, put the subject at increased risk by participating in
             the study or would have interfered with the conduct or planned analyses of the study.