A Trial to Treat Polyomavirus Infections (BKPyV) in Kidney and Simultaneous Kidney Pancreas Transplant Recipients (BEAT-BK)

The University of Queensland

Status and phase: Enrolling; Phase 3

Conditions: Kidney Transplant Failure and Rejection; Kidney Transplant Infection; BK Viremia

Treatments: Drug: Immunosuppression reduction/modification + intravenous immunoglobulin; Other: Immunosuppression reduction/modification

Study type: Interventional

Funder types: Other

Identifiers

NCT05325008

AKTN 20.07

Details and patient eligibility

About

BEAT-BK will see the effect of immunosuppression reduction/modification with and without IVIG on BKPyV infection, allograft function, allograft loss, acute transplant rejection, immunosuppression load and death in kidney and simultaneous kidney pancreas transplant recipients with polyomavirus infections (BKPyV).

Full description

BKPyV infection is a rare but also devastating disease in kidney and SPK transplant recipients. Immunosuppression used in transplantation minimises the risk of acute rejection and eventual graft loss, but suppression of the immune system increases the risk of opportunistic infections and reactivation of latent viruses causing disease, such as BKPyV infection. Therefore, balancing the complications of excessive versus inadequate immunosuppression is a key priority for patients and health professionals. The BEAT-BK trial is designed through a structured, consensus process, and informed by the pilot observational data generated by the investigators. The conventional immunosuppression reduction approach may include judicious reduction in the doses of calcineurin inhibitors and anti-proliferative agents, or conversion to less potent immunosuppression therapy such as a switch from tacrolimus to cyclosporine, or mycophenolate to azathioprine. While adjuvant therapy is not commonly used, 63% of participants would consider IVIG as a 'rescue', when conventional therapy has failed, or the graft function is deteriorating rapidly. IVIG is a nondepleting agent containing natural antibodies with potential antiviral and immunomodulatory properties. It is used against some chronic infections (Epstein-Barr virus) and the treatment of antibody-mediated rejection in kidney transplantation. In BKPyV infection, the certainty of the evidence for IVIG is very low due to imprecision, and high risk of bias (small, case series, retrospective cohorts), but it holds promise based on findings from our observational data (n = 50). Recipients with BKPyV-DNAemia who received IVIG as adjuvant therapy were more likely to achieve complete viral clearance at 12 months (77.3% vs. 33.3%, p < 0.01) and less likely to relapse (11% vs. 27.3%, p=0.01) compared to recipients who received conventional therapy alone.

Enrollment: 280 estimated patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 2 years or above
2. Have received a kidney or simultaneous pancreas-kidney transplant
3. Have BKPyV-Viremia (detected by RT-PCR) with a viral count ≥ 5,000 copies per mL, or histological confirmation of BKPyVAN, within 3 weeks prior to randomisation.
4. Be able to provide informed consent or consent given by a parent or guardian (if age <18 years) or other authorised person

Exclusion criteria

1. Contraindications to receiving IVIG as a treatment
2. Current active acute rejection (≤ 3 months prior)
3. Treating clinicians would regard as unsafe to be enrolled
4. Limited life expectancy (< 12 months)
5. Receiving Belatacept as part of their immunosuppression protocol
6. Currently undergoing or who have previously received, viral-specific T-cell therapy for BK viremia
7. Prior infection and treatment for BKPyV-Viremia
8. Received IVIG treatment in the past with last IVIG treatment < 4 weeks prior to randomisation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

280 participants in 2 patient groups

Immunosuppression reduction/modification + Intravenous Immunoglobulin

Experimental group

Description:

Receives Immunosuppression reduction/modification + Intravenous Immunoglobulin

Treatment:

Drug: Immunosuppression reduction/modification + intravenous immunoglobulin

Immunosuppression reduction/modification

Other group

Description:

Receives Immunosuppression reduction/modification as part of standard of care.

Treatment:

Other: Immunosuppression reduction/modification