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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Adenovirus Infection

Intervention / Treatment
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* Drug: BCV


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCV 0.2mg/kg BIW<br>BCV: 0.2 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks. | Drug: BCV<br>* 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<br>|
| Experimental: BCV 0.3mg/kg BIW<br>BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks. | Drug: BCV<br>* 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<br>|
| Experimental: BCV 0.4 mg/kg BIW<br>BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for a minimum of 4 weeks. | Drug: BCV<br>* 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<br>|
| Experimental: BCV 0.4 mg/kg QW<br>BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 for a minimum of 4 weeks. | Drug: BCV<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with BCV treatment-related adverse events as assessed by NCI CTCAE v5.0 |  | From initiation of BCV administration up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change AdV viremia in plasma measured from baseline up to 4 weeks |  | From initiation of BCV administration up to 4 weeks | 
| Change of Time-averaged [AdV AAUC] for AdV viremia in plasma from baseline up to 4 weeks |  | From initiation of BCV administration up to 4 weeks | 
| Peak AdV viral load in plasma after onset of AdV viremia up to 4 weeks |  | From initiation of BCV administration up to 4 weeks |