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Evaluate Tolerability and Safety of BD03 for Prevention of CMV and BKV Reactivation in Kidney Transplant Recipient

Primary Purpose

Cytomegalovirus Infections, Preventation of Cytomegalovirus Reactivation, BK Virus Infection

Status

Unknown status

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

BD03

About this trial

This is an interventional prevention trial for Cytomegalovirus Infections focused on measuring CMV, BKV, CMV Reactivation, BKV Reactivation, DNA Vaccine, Kidney transplant, Cytomegalovirus, BK virus

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Samsung Medical centerRecruiting
Seoul St.Mary's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BD03

Arm Description

This study will be comprised of 3+3 dose escalation design with three dose levels, 0.6mg (cohort1), 2mg(cohort2), 6mg(cohort3). Decision to increase dose will be guided by occurrence of DLT (dose limiting toxicity) evaluated 1week after the second injection (5weeks after first injection)

Outcomes

Primary Outcome Measures

Tolerability as measured by dose-limiting toxicities (DLTs)

An event will be considered a DLT if the event is reasonably related to study treatment during the 5weeks of treatment, and meets the following criteria: Any Grade 3 or greater toxicity per CTCAE 4.03 that would be considered dose-limiting except for those associated with kidney failure, Grade 3 or greater Creatine kinase increase that is not accompanied with Rhabdomyolysis, and any other Grade3 or greater toxicity that exists before participation of this study.

Secondary Outcome Measures

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.

To evaluate the immunogenicity of BD03. ELISPOT assay of specific T cell responses to CMV and BKV antigens.

Antibody response to CMV gB antigen

To investigate antibody level measured by Enzyme-Linked ImmunoSorbent Assay(ELISA)

Antibody response to BKV VP1 antigen

To investigate antibody level measured by Enzyme-Linked ImmunoSorbent Assay(ELISA)

Change of CMV and BKV plasma viral load over time

To investigate change of CMV and BKV plasma viral load over time

Full Information

NCT ID

NCT03576014

First Posted

May 25, 2018

Last Updated

June 21, 2018

Sponsor

SL VAXiGEN

Collaborators

SL BIGEN

1. Study Identification

Unique Protocol Identification Number

NCT03576014

Brief Title

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

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Unknown status

Study Start Date

April 27, 2018 (Actual)

Primary Completion Date

January 30, 2019 (Anticipated)

Study Completion Date

July 24, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SL VAXiGEN

Collaborators

SL BIGEN

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

BD03

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

BD03

Intervention Description

BD03 is to be administered intramuscularly 6 weeks and 2 weeks prior to kidney transplant and 2~4 weeks after the transplant.

Primary Outcome Measure Information:

Title

Tolerability as measured by dose-limiting toxicities (DLTs)

Description

Time Frame

5 weeks

Secondary Outcome Measure Information:

Title

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.

Description

To evaluate the immunogenicity of BD03. ELISPOT assay of specific T cell responses to CMV and BKV antigens.

Time Frame

Up to 30 weeks post-dose

Title

Antibody response to CMV gB antigen

Description

To investigate antibody level measured by Enzyme-Linked ImmunoSorbent Assay(ELISA)

Time Frame

Up to 30 weeks post-dose

Title

Antibody response to BKV VP1 antigen

Description

To investigate antibody level measured by Enzyme-Linked ImmunoSorbent Assay(ELISA)

Time Frame

Up to 30 weeks post-dose

Title

Change of CMV and BKV plasma viral load over time

Description

To investigate change of CMV and BKV plasma viral load over time

Time Frame

Up to 30 weeks post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sujin Kim, Ph.D

Phone

031-628-2182

sjkim@slvaxigen.com

First Name & Middle Initial & Last Name or Official Title & Degree

Mincheol Kim

Phone

031-628-2182

mckim@slvaxigen.com

Facility Information:

Facility Name

Samsung Medical center

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sungjoo Kim, M.D, Ph.D

Facility Name

Seoul St.Mary's Hospital

City

Seoul

ZIP/Postal Code

06591

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chulwoo Yang, M.D, Ph.D

12. IPD Sharing Statement

Citations:

PubMed Identifier

23465010

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.

Results Reference

background

PubMed Identifier

19845597

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.

Results Reference

background

Learn more about this trial

Evaluate Tolerability and Safety of BD03 for Prevention of CMV and BKV Reactivation in Kidney Transplant Recipient

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