Phase 2 Study to Evaluate Brincidofovir for the Prevention of Adenovirus Disease
Condition: Adenovirus Disease
MeSH terms: Adenoviridae Infections
Intervention: Brincidofovir; Placebo
Intervention description: Adult subjects: 200mg BCV administered as 50mg tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
Pediatric subjects: 4mg/kg BCV (not to exceed a total single dose of 200mg) administered using a 10 mg/mL liquid formulation taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).; Adult subjects: Matching placebo tablets taken orally either once weekly (QW; 4 tablets) or twice weekly (BIW; 2 tablets).
• Pediatric subjects: Matching liquid placebo taken orally either QW (as 4 mg/kg) or BIW (as 2 mg/kg).
Intervention MeSH terms: Brincidofovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 52.0
Sex: All
Minimum age: 3 Months
Maximum age: 75 Years
Healthy volunteers: No
Keywords: AdV; Hematopoeitic Stem Cell Transplant; HSCT

Summary:

      This study was designed to assess the safety and efficacy of preemptive treatment with oral
      brincidofovir (BCV), as compared to placebo, for the prevention of adenovirus (AdV) disease
      in recipients of hematopoietic stem cell transplantation (HCT) with asymptomatic AdV viremia.
    

Eligibility criteria:

        Inclusion Criteria

        For inclusion into the study, subjects were required to fulfill all of the following
        criteria:

          1. Were males or female aged ≥3 months to ≤75 years.

          2. Received an allogeneic hematopoietic stem cell transplant (HCT).

          3. Had positive serum adenovirus (AdV) PCR (>100 copies/mL) as measured by the central
             laboratory (unless the subject developed AdV disease while participating in the
             prescreening activities and after concurrence from the Chimerix medical monitor or
             designee).

          4. Was on dialysis during treatment if he/she had an estimated glomerular filtration rate
             (eGFR) ≤30 mL/minute.

          5. Subject or guardian(s) were willing to comply with the protocol.

          6. Subject or guardian(s) were willing and able to understand the informed
             consent/assent.

          7. Female subjects of child-bearing potential must have had a negative pregnancy test and
             must have agreed to use 2 acceptable methods of birth control throughout the study
             with at least 1 being a barrier method. Sexually active males of procreation potential
             must have been able and willing to se a reliable and medically approved contraceptive
             method throughout the study. At least 1 barrier method of contraception must have been
             used.

        Exclusion Criteria

        Subjects meeting any of the following exclusion criteria were excluded from participation
        in the study:

          1. Had possible, probable, or definitive AdV disease (unless the subject developed
             probable or definitive AdV disease while participating in prescreening activities and
             after concurrence from he Chimerix medical monitor or designee).

          2. Had suspected gut graft versus host disease that was not biopsy-proven (subjects with
             a biopsy performed were included in the study).

          3. Had an eGFR ≤30 mL/minute and was not currently on dialysis.

          4. Had an alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of
             normal (ULN), total bilirubin ≥2 x the ULN, or conjugated (direct) bilirubin ≥1.5 x
             the ULN.

          5. Had a condition that prevented oral dosing of study drug.

          6. Was HIV antibody positive, based upon available medical records.

          7. Had ocular hypotony, uveitis, or retinitis or any other intraocular pathology that
             would have predisposed the subject to 1 of these conditions.

          8. Had participated in another clinical study of an investigational drug/biologic or was
             exposed to an investigational drug/biologic within 30 days of enrollment without the
             prior written approval of the Chimerix medical monitor or designee. For subjects who
             were participating in any clinical study involving non-investigational drugs and/or
             biologics, the investigator must have obtained approval from the Chimerix medical
             monitor or designee prior to enrolling the subject.

          9. Was pregnant or breast-feeding or intended to conceive during the course of the study,
             including the follow-up period after drug discontinuation.

         10. Had known immunologic hypersensitivity to cidofovir (CDV) or brincidofovir (BCV) drug
             or any of its excipients.

         11. Had a history of illicit drug use or alcohol abuse within the previous 6 months.

         12. Had any medical condition that, in the opinion of the investigator, might have
             interfered with the subject's participation in the study, posed an added risk for the
             subject, or confounded the assessment of the subject (e.g. severe cardiovascular,
             central nervous system or pulmonary disease).

         13. Received BCV, CDV, ribavirin, or leflunomide within the previous 14 days.

         14. Was receiving or was anticipated to need treatment with digoxin that could not have
             been withheld for the duration of BCV therapy.

        Any exemptions to the protocol inclusion or exclusion criteria, as applicable, for subjects
        who developed probably or definitive AdV disease while participating in prescreening
        activities must have been discussed with and approved by the Chimerix medical monitor or
        designee before the subject was allowed to receive open-label BCV therapy.