Study to Confirm of the Safety and Tolerability of Brincidofovir in Subjects With BK Virus Infection (Viremia) After Kidney Transplantation

Phase II, Open-label, Randomized, Multiple Ascending Dose Confirmation of the Safety and Tolerability of Brincidofovir in Subjects With BK Virus Infection (Viremia) After Kidney Transplantation (BASTION)

This is a Phase II, multicenter, open-label, randomized, standard of care (SOC) controlled, multiple ascending dose study to assess the safety and tolerability of IV Brincidofovir (BCV) in subjects with BKV infection after kidney transplantation. The study will be conducted at multiple study sites in several countries including Australia and Japan. Subjects who meet eligibility criteria will be enrolled in the study and will be randomized and assigned to BCV or SOC (defined as use of the same immunosuppressant administered during prescreening) before receipt of the first dose of study drug in both the Dose Escalation Phase and the Expansion Phase.

Study Overview

• Status: Terminated
• Conditions: BK Virus Infection; Kidney Transplantation; Nephropathy
• Intervention / Treatment: Drug: Brincidofovir

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, at least 18 years of age at the time of signing the informed consent at screening.
• Kidney transplant recipient. "BK viral load increase and ≥ 3.6 log IU/mL" at 2 weeks post immunosuppression reduction or "BK viral load does not decrease by ≥ 0.3 log IU/mL" at 4 weeks post immunosuppression reduction during prescreening.

(Note: Immunosuppressant reduction needs to be continued during the screening period).

• eGFR ≥ 30 mL/min.
• Subjects under immunosuppression with tacrolimus, MMF/Myfortic, and/or corticosteroid.

Exclusion Criteria:

• Subjects who weigh ≥ 120 kg.
• National Institutes of Health/NCI CTCAE Grade 2 or higher diarrhea (ie, increase of ≥ 4 stools per day over usual pretransplant stool output) within 7 days before Day 1.
• Poor clinical prognosis, including active malignancy or use of vasopressors other than low dose (eg, ≤ 5 μg/kg/min) dopamine for renal perfusion within 7 days before Day 1.
• Use of renal replacement therapy within 7 days before Day 1.
• History of intolerance to cidofovir or related compounds (ie, other nucleotide derivatives [adefovir or tenofovir])

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase: Cohort 1: BCV 0.3 mg/kg BIW; BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for 8 weeks (up to a maximum of 14 weeks).	Drug: Brincidofovir; BCV 0.3 mg/kg BIW or 0.4 mg/kg BIW administered as a continuous IV infusion over 2 hours; Other Names: SyB V-1901; BCV
Experimental: Dose Escalation Phase: Cohort 2: 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 8 weeks (up to a maximum of 14 weeks).	Drug: Brincidofovir; BCV 0.3 mg/kg BIW or 0.4 mg/kg BIW administered as a continuous IV infusion over 2 hours; Other Names: SyB V-1901; BCV
Experimental: Expansion Phase: BCV Recommended dosage regimen in the Dose Escalation Phase; BCV: Recommended dosage administered as a continuous IV infusion over 2 hours on Day1 and Day4 for 8 weeks (up to a maximum of 14 weeks).	Drug: Brincidofovir; BCV 0.3 mg/kg BIW or 0.4 mg/kg BIW administered as a continuous IV infusion over 2 hours; Other Names: SyB V-1901; BCV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of TEAEs of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 severity and serious adverse events; Incidence of treatment-related TEAEs; Incidence of adverse events (AEs) requiring permanent discontinuation of BCV; Absolute and changes over time in safety laboratory parameters (ie, hematology, blood chemistry, and urinalysis)	from the time of administration of the first dose of study drug through the follow-up visit(up to 14 weeks (treatment period) and 30 days (follow-up period))
Antiviral Effects	Change from baseline in BK viral load in plasma measured through follow-up for each subject. Change from baseline in BK viral load in urine measured through follow-up for each subject. Peak BK viral load in plasma from Week 2 Day 1 through follow-up for each subject. Time-averaged area under the viremia-time curve for BK viral load in plasma from baseline through follow-up for each subject.	From baseline to follow-up visit(up to 14 weeks (treatment period) and 30 days (follow-up period))

Collaborators and Investigators

• Sponsor: SymBio Pharmaceuticals
• Investigators: Study Director: Carolyn Yanavich, SymBio Pharmaceuticals Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Actual): April 13, 2023
• Study Completion (Actual): April 13, 2023

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 22, 2022
• First Posted (Actual): August 23, 2022

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Kidney transplantation; BK Virus; Nephropathy
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infections; Communicable Diseases; Virus Diseases; Kidney Diseases; Viremia; Anti-Infective Agents; Antiviral Agents; Brincidofovir
• Other Study ID Numbers: BCV-BN01

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No