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

JRCT ID: jRCT2041220056

Registered date:18/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: BK virus infection (viremia) after kidney transplantation
• Date of first enrollment: 31/10/2022
• Target sample size: 36
• Countries of recruitment: Australia,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

The study is composed of a Dose Escalation Phase and an Expansion Phase. A total of approximately 36 male or female subjects aged 18 years and older will be enrolled: 8 subjects (BCV: 6 subjects; SOC: 2 subjects) in each of 2 cohorts in the Dose Escalation Phase and 20 subjects (BCV: 14 subjects; SOC: 6 subjects) in the Expansion Phase.
Dose Escalation Phase:
- Cohort 1: BCV 0.3 mg/kg twice weekly
- Cohort 2: BCV 0.4 mg/kg twice weekly
- SOC: Immunosuppression reduction and monitoring
Expansion Phase:
- BCV: Recommended dosage regimen in the Dose Escalation Phase
- SOC: Immunosuppression reduction and monitoring

Outcome(s)

Primary Outcome

Safety Endpoints:
- Incidence of treatment-emergent adverse events (TEAEs), particularly those 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)
Antiviral Effects Endpoints:
- 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

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Male or female, at least 18 years of age at the time of signing the informed consent at screening.
2. Kidney transplant recipient.
3. "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).
4. eGFR >= 30 mL/min.
5. Subjects under immunosuppression with tacrolimus, MMF/Myfortic, and/or corticosteroid.

Exclude criteria

1. Subjects who weigh >= 120 kg.
2. 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.
3. Poor clinical prognosis, including active malignancy or use of vasopressors other than low dose (eg, =< 5 ug/kg/min) dopamine for renal perfusion within 7 days before Day 1.
4. Use of renal replacement therapy within 7 days before Day 1.
5. History of intolerance to cidofovir or related compounds (ie, other nucleotide derivatives [adefovir or tenofovir]).

Related Information

• Primary Sponsor: Hoshino Yuji
• Secondary ID(s): NCT05511779