A Study to Investigate DSA Rebound in Patients Treated With Imlifidase Prior to Transplantation

Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly specific for IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG. Clinical studies with imlifidase have demonstrated that the treatment enables transplantation in patients otherwise highly unlikely to be transplanted, by converting a positive crossmatch to a negative.

However, as with other desensitization methods, DSA tend to reappear within weeks after treatment and transplantation, which may cause AMR and increased risk of graft loss. In this study, treatment with imlifidase in combination with approved drugs that prevent or suppress DSA rebound by targeting antibody-producing plasma-cells and their B-cell precursors is suggested. These drugs include (i) bortezomib, a proteasome inhibitor which has activity against mature plasma cells, the source of DSA, (ii) belatacept, a fusion protein which is crucial in blocking T-cell co-stimulation and which is effective in reducing de novo DSA generation in humans, (iii) rituximab, an anti-CD20 monoclonal antibody that targets B-cells and which is an immunomodulatory agent, and (iv) intravenous immunoglobulin (IVIg) which is commonly used in desensitization regimens and for the treatment of AMR.

After being informed about the study and potential risks, all patients giving written informed consent will undergo a 2-week screening period to determine eligibility for study entry. Patients who meet the eligibility requirements will then start treatment with belatacept and bortezomib about 3 weeks prior to the imlifidase infusion and transplantation. Rituximab will be initiated 8 days after transplantation and IVIg 10 days after transplantation. Induction and maintenance immunosuppression will also be administered. The patients will be hospitalized for approximately 2 weeks following transplantation and after that 9 follow-up visits to the clinic will take place up to 6 months after transplantation.