A Phase 2a Study of IV BCV in Subjects With Adenovirus Infection (ATHENA)

A Phase IIa, Open-label, Multiple Ascending Dose Confirmation Study of the Safety and Tolerability of Intravenous Administration of Brincidofovir in Subjects With Adenovirus Infection

The purpose of this study is to determine the Dose from the safety and tolerability of intravenous Brincidofovir (BCV, SyB V-1901) using multiple ascending doses in subjects with Adenovirus infection.

This is a Phase IIa, open-label, multiple ascending dose confirmation, multicenter study to evaluate the safety and tolerability of intravenous Brincidofovir (BCV, SyB V-1901) 0.2 mg/kg, 0.3 mg/kg, or 0.4 mg/kg dosed BIW or 0.4 mg/kg dosed QW (Cohorts 1 to 4) in adult and pediatric subjects with AdV viremia. A total of 24 subjects aged 2 months and older will be enrolled: 6 subjects to each Cohort.

BCV: 0.2 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks.

BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks.

BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks.

BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 for a minimum of 4 weeks.

BCV 0.2 mg/kg BIW, 0.3 mg/kg, or 0.4 mg/kg dosed BIW or 0.4 mg/kg dosed QW via IV infusion for 2 hours

Inclusion Criteria: Male or female, aged 2 months and older at the time of informed consent. AdV DNA viremia >10,000 copies/mL from a single sample, or 2 samples greater than 48 hours apart with the second result higher than the first and both greater than 1000 copies/mL, from the data obtained from the designated central virology laboratory of the local laboratory using the blood sample(s) collected informed consent has been obtained and within 7 days prior to Day 1 (AdV DNA viremia results collected within the 7 day window, but prior to consent may be used if the Informed Consent Form (ICF) signed by the subject provides approval) . Either (a) have disseminated AdV disease or (b) have an underlying immunocompromised state, and have asymptomatic AdV infection or localized AdV disease. In the judgment of the investigator, be in a serious condition to be treated with intravenous cidofovir for AdV. Exclusion Criteria: Subjects who weigh ≥120 kg. NIH/NCI CTCAE (United States [US] National Institutes of Health [NIH]/National Cancer Institute) Grade 2 or higher diarrhea (i.e., increase of ≥ 4 stools per day over usual pre-transplant stool output) within 7 days prior to Day 1. NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1. NIH Stage 2 or higher acute GVHD of the liver function (i.e., bilirubin >3 mg/dL [SI: >51 μmol/L]) within 7 days prior to Day 1. NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea >556 mL/m2/day for pediatric subjects [or >1000 mL/day for young adults as applicable, at centers in the United States only], or severe abdominal pain with or without ileus) within 7 days prior to Day 1.