Assess Safety, Tolerability and Pharmacokinetics of AntiBKV in Healthy Adult Volunteers.
Condition: BK Virus Nephropathy
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): AntiBKV; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): AntiBKV neutralising antibody; Solution with no active ingredients
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single-blind, partially randomized, placebo-controlled study in healthy volunteers. Approximately 40 to 56 healthy adult participants are planned to be enrolled in 7 cohorts of 4 to 8 participants, randomized in a 3:1 ratio to receive AntiBKV or placebo
Masking: Single (Participant)
Primary purpose: Prevention