This Phase 3 multi-center, randomized, open-label study will assess efficacy of IV BCV,
compared to IV CDV, in allo-HCT subjects with AdV viremia. Randomized subjects will be
treated for up to a maximum of 12 weeks of therapy for both arms. Primary efficacy
assessment will be performed at W5D1. Consistent with ECIL guidelines for high-risk
patients, AdV viremia will be assessed weekly. Subjects randomized to receive BCV or CDV
are treated until AdV DNA is confirmed to be undetectable in plasma for two consecutive
tests 7 days apart, or until Week 12 post W1D1, whichever occurs first. Subjects will
continue BCV or CDV as long as AdV viremia is detectable, contingent on tolerability,
until viremia clears, or the subject reaches a maximum duration of 12 weeks of study drug
treatment.
Subjects will receive assigned randomized therapy until time of AdV virological success
plus 2 weeks, for up to a maximum of 12 weeks. All subjects will be followed through 24
weeks. All study visits and follow-up assessments must be completed regardless of the
study drug treatment duration. All subjects are considered on study through the Week 24
follow-up visit.
For subjects who achieve virological success from their initial randomized study drug
treatment and experience an AdV viremia recurrence, repeat treatment with their
randomized study drug is allowed. There is no cross-over study drug treatment allowed in
this study and subjects can only receive retreatment with their randomized study drug.
Subjects who stop study drug therapy due to confirmed undetectable AdV viremia may
re-initiate study drug treatment if AdV viremia is subsequently confirmed at ≥ 1000 IU/mL
by the designated central virology laboratory (recurrence). For the purposes of
re-initiating study drug therapy, "confirmed viremia ≥ 1000 IU/mL" is defined as two
consecutive results ≥ 1000 IU/mL from the designated central laboratory, with the second
sample drawn at least 48 hours after the first sample.
Subjects who permanently discontinue study drug therapy for toxicity reasons are not
eligible to re-initiate study drug dosing. Study procedures are to be followed during
these Retreatment visits as applicable for BCV and CDV outlined in the schedule of
assessments (SOA).
An independent Data Safety Monitoring Board (DSMB) will review accumulated safety data
for this study when total combined enrollment in both arms is approximately 25% (45
subjects) and 50% (90 subjects). They will also review adverse events on an ongoing
basis. They will make recommendations to the Sponsor based on review of these safety
data. Further details regarding data safety monitoring guidelines will be included in the
DSMB Charter. The DSMB will make determinations regarding continued enrolment and/or
stopping the study for safety reasons.
An Endpoint Adjudication Committee (EAC) will be convened to evaluate baseline diagnosis
and AdV disease clinical response as outlined in the EAC charter.
