BK Virus Infection, Kidney Transplantation, Nephropathy
Conditions
Keywords
BK Virus, Nephropathy, Kidney transplantation
Brief summary
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.
Interventions
DRUGBrincidofovir
BCV 0.3 mg/kg BIW or 0.4 mg/kg BIW administered as a continuous IV infusion over 2 hours
Sponsors
SymBio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[adefovir or tenofovir\])
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | 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)) | * 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) |
| Antiviral Effects | From baseline to follow-up visit(up to 14 weeks (treatment period) and 30 days (follow-up period)) | 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. |
Countries
Japan
Outcome results
None listed