Clinical trial NCT03576014: Evaluate Tolerability and Safety of BD03 for Prevention of CMV and BKV Reactivation in Kidney Transplant Recipient
Official title: A Prospective, Open, Dose-escalation, Multi-center, Phase 1 Trial to Evaluate Tolerability and Safety of Intramuscularly Administered BD03, a DNA Vaccine for Prevention of CMV and BKV Reactivation in Kidney Transplant Recipient
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cytomegalovirus Infections
Preventation of Cytomegalovirus Reactivation
BK Virus Infection
Preventation of BK Virus Reactivation
Keywords: CMV
BKV
CMV Reactivation
BKV Reactivation
DNA Vaccine
Kidney transplant
Cytomegalovirus
BK virus
Lead sponsor: SL VAXiGEN
Sponsor class: INDUSTRY
Collaborators: name: SL BIGEN
First posted: 2018-07-03
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study is a phase I, open-label study to determine recommended phase 2 dose (RP2D) for the BD03 vaccination in kidney transplant recipients. The recommended dose will be selected based on the safety and tolerability profiles observed.

Detailed description: It is reported that CMV and BKV infection and/or reactivations are associated with mortality and morbidity of kidney transplant recipient, and occurrence of PyVAN in kidney transplant recipients.

BD03 is a DNA vaccine that consists of 3 plasmid DNAs encoding CMV antigens, BKV antigens and genetic adjuvant. It is expected to express antigen specific T-cell immune response, and ultimately prevent activation of both viruses. Plasmid DNA that encode CMV and BKV antigens are fused with tPA and Flt-3L to promote antigen specific immune response.

Patient scheduled to receive kidney transplant from living donor are enrolled in this study. Eligible subjects will receive BD03 intramuscularly by electroporator three times on 6 weeks and 2 weeks prior to kidney transplant and 2\~4 weeks after the transplant.

This study will be comprised of 3+3 dose escalation scheme and starting dose is 0.6mg and dose will be increased to 2mg and 6mg.

Occurrence of dose limiting toxicities observed until 1 week after second injection (1week before kidney transplant) will guide whether to increase a dose.

After third injection of BD03, follow up visits are done for 18 weeks.

Eligibility criteria: Inclusion Criteria:

* Age of ≥ 19
* Body Mass Index ≤ 35
* Weight ≥ 40kg

Exclusion Criteria:

* CMV IgG seronegative patient
* Patient scheduled for retransplant of kidney
* Patient known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
* Patient expected to receive T-cell depleting agents or rituximab
* Patient with history of splenectomy
* Patient with CMV related disease or shows active CMV infection or who has been treated with CMV related disease or CMV infection within 3 months from consent date.
* Patient expected to undergo CMV prophylaxis using anti-virals or immunoglobulins.
* Patient who has hypersensitivity to BD03 or components of BD03.
* Patient with history of epilepsy or seizure with the last 2 years
* Patients with pre-excitation syndrome or any other disease who would be considered ineligible for electroporation injection.
* Patient with blood coagulation disorder who would be considered ineligible for electroporation injection
* Patient with injection site thickness greater than 40mm
* Patient with artificial implant near injection site
* Pregnant or breast-feeding female patient
* Female subject or partner of male subject with child bearing potential and who has not agreed to sexual abstinence
* Patient who has participated in any other clinical trial within 30 days
* Patient who has any clinically meaningful disease investigator's judgement to prevent participating in this study

Primary outcomes:
measure: Tolerability as measured by dose-limiting toxicities (DLTs)
timeFrame: 5 weeks
Secondary outcomes:
measure: Proportion of subjects whose Spot Forming Units per unit PBMC are tripled compared to base line measurements and subjects whose Spot Forming Units of each antigen in 10^6 PBMC are greater than 50.
timeFrame: Up to 30 weeks post-dose
measure: Antibody response to CMV gB antigen
timeFrame: Up to 30 weeks post-dose
measure: Antibody response to BKV VP1 antigen
timeFrame: Up to 30 weeks post-dose
measure: Change of CMV and BKV plasma viral load over time
timeFrame: Up to 30 weeks post-dose
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical center
city: Seoul
country: Korea, Republic of
facility: Seoul St.Mary's Hospital
Study officials:
References:
citation: Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:179-88. doi: 10.1111/ajt.12110.
citation: Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155. doi: 10.1111/j.1600-6143.2009.02834.x.