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.

Study Overview

• Status: Recruiting
• Conditions: Adenovirus Infection
• Intervention / Treatment: Drug: BCV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kohji Shimasaki; Phone Number: +81-3-6684-6616; Email: MedInfo@symbiopharma.com
• Study Contact Backup: Name: Rochelle Maher; Phone Number: +1-917-656-6951; Email: maher@symbiopharma.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Research Site
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Research Site
    • San Francisco, California, United States, 94158
      • Recruiting
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCV 0.2mg/kg BIW; 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; 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
Experimental: BCV 0.3mg/kg BIW; 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; 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
Experimental: BCV 0.4 mg/kg BIW; 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; 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
Experimental: BCV 0.4 mg/kg QW; BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 for a minimum of 4 weeks.	Drug: BCV; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: SymBio Pharmaceuticals

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Infections; Communicable Diseases; Adenoviridae Infections
• Other Study ID Numbers: BCV-PA01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No