A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT

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.

Inclusion criteria

• Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
• Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
• In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
• Has adenoviremia, based on any of:

• AdV viremia DNA ≥10,000 IU/mL, OR
• Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR
• AdV viremia DNA of ≥1,000 IU/mL, AND

• Lymphocyte count <180/mm3, OR 2. Received T cell depletion, cord blood, or haploidentical transplant, OR 3. prior alemtuzumab, OR 4. anti-thymocyte globulin (ATG)

Exclusion criteria

• Subject received an allo-HCT with a matched sibling donor
• Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
• Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
• Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
• Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.