Assess Safety, Tolerability and Pharmacokinetics of AntiBKV in Healthy Adult Volunteers.
brief summary
BK virus (BKV) is a member of the polyomavirus family with a prevalence of up to 90% in the general population. In immunocompromized individuals, such as kidney transplant recipients (KTRs) who receive immunosuppressant therapy to prevent graft rejection, BKV turns into an opportunistic pathogen. BK viremia has been reported to occur in 10-30% of KTRs. BKV is recognized as a leading cause of impaired graft function and premature transplant loss, and is therefore a serious condition in kidney transplant patients. At present, there are no effective agents specifically against BKV available and thus no standard treatment that can effectively reduce or prevent BKV infection/reactivation after renal transplantation. Therefore, the proposed indication for the AntiBKV neutralizing antibody is the treatment of BK virus infections and prevention of BK virus associated complications in KTRs. This study has been designed to evaluate the safety, tolerability, and pharmacokinetic of ascending doses of AntiBKV, a fully human highly neutralising antibody against BKV, administered as a single or multiple intravenous infusions to healthy adult participants. The data obtained in this study will provide the basis for further clinical development of AntiBKV.
detailed description
BK virus (BKV) is a member of the polyomavirus family with a prevalence of up to 90% in the general population. It lies dormant and rarely causes disease in healthy individuals. However, in immunocompromized individuals, such as kidney transplant recipients (KTRs) who receive immunosuppressant therapy to prevent graft rejection, BKV turns into an opportunistic pathogen.
BKV replication can be detected before the development of BK virus associated nephropathy (BKVAN) and first virus shedding is detected in the urine. BK viremia has been reported to occur in 10-30% of KTRs. BKVAN progression is detected by a median of 8 weeks after establishment of the persistent viremia, and occurs most commonly in the first 2 years post-transplantation or following treatment of graft rejection. BKV infection/reactivation in these patients can lead to progression to BKVAN in up to 10% of all KTRs, while ultimately leading to graft dysfunction in 38% of patients and loss in 20% of patients presenting with BK viremia. BKV is recognized as a leading cause of impaired graft function and premature transplant loss, and is therefore a serious condition in kidney transplant patients.
At present, there are no effective agents specifically against BKV available and thus no standard treatment that can effectively reduce or prevent BKV infection/reactivation after renal transplantation.
The current standard of care after kidney transplantation involves prospective screening for BKV reactivation post-transplantation and subsequent reduction of immunosuppression to strengthen immune responses against BKV. Although reduction of immune suppression is a widely accepted management option, approaches for dose tapering differ with no consensus existing regarding when and which agent should be reduced or stopped following a diagnosis of BKV infection.
The proposed indication for the AntiBKV neutralizing antibody is the treatment of BK virus infections and prevention of BK virus associated complications in KTRs. In KTRs, the detection of the BK virus in the blood has been found to be strongly associated with the development of BKVAN and the grade of BK viremia correlates with the onset of the renal disease. A decrease of the virus load significantly reduces the chance for progression to BKVAN. Treatment of BK viremia with AntiBKV in KTRs with BKV infection/reactivation would allow for continued optimal immunosuppression to prevent graft rejection in these patients.
This study is the first clinical study to be conducted with AntiBKV and has been designed to evaluate the safety, tolerability, and pharmacokinetic of ascending doses of AntiBKV administered as single or multiple intravenous infusions to healthy adult participants. The data obtained in this study will provide the basis for further clinical development of AntiBKV.
official title
A Phase 1, Single-blind, Partially Randomized, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Intravenous Doses of AntiBKV in Healthy Adult Volunteers.