NCT04935177

Renal Function in Highly Sensitized Patients 1 Year After Desensitization With Imlifidase Prior to DD Kidney Tx

An Open-label, Controlled, Randomized Phase 3 Trial Evaluating 12-month Kidney Function in Highly Sensitized (cPRA ≥99.9%) Kidney Tx Patients With Positive XM Against a Deceased Donor, Comparing Desensitization Using Imlifidase With SoC

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Hansa Biopharma AB · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

An open-label, controlled, randomized Phase 3 trial evaluating 12-month kidney function in highly sensitized (cPRA ≥99.9%) kidney transplant patients with positive crossmatch against a deceased donor, comparing desensitization using imlifidase with standard of care

Detailed description

After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry. Once an organ offer is received, a virtual crossmatch (vXM) is performed. If the crossmatch is considered predictive of a positive flow cytometry crossmatch (FCXM), the patient will be evaluated if eligible to receive the desensitization currently in use at the study site. Subsequently the patient will be randomized in a 1:1 ratio to the imlifidase or the control arm. If the patient is randomized to the imlifidase arm, the organ will be accepted and shipped, and the patient will proceed to imlifidase treatment (generally within 24 h prior to transplantation) followed by transplantation. If the patient is randomized to the control arm, transplantation made possible by the local desensitization regimen will occur. If the institution-specific desensitization protocol is deemed not to be successful, the organ offer will be turned down, and the patient will remain active on the waiting list and remain in the trial, while the kidney will be allocated to another recipient through the kidney allocation system (KAS). All transplanted patients will receive induction therapy and maintenance immunosuppression. All patients will be followed for 12 months. Estimated glomerular filtration rate (eGFR) will be assessed 12 months after randomization as the primary endpoint reasonably likely to predict a clinical benefit in patient survival. All patients with donor specific antibodies (DSA) are at risk of developing antibody-mediated rejection (AMR). Imlifidase removes DSA quickly and efficiently at the time of transplantation but, as with other desensitization methods, the antibodies are expected to re-occur after transplantation. In the imlifidase treatment arm, and for desensitized control arm patients, protocol kidney biopsies will be performed at the time of transplantation and at 1 year after transplantation.

Conditions

• Kidney Transplantation in Highly Sensitized Patients

Interventions

Type	Name	Description
DRUG	Imlifidase	Imlifidase is an immunoglobulin G (IgG)-degrading enzyme of Streptococcus pyogenes that is highly selective towards IgG. The cleavage of IgG generates one F(ab')2- and one homodimeric Fc-fragment and efficiently neutralizes Fc-mediated activities of IgG.
PROCEDURE	PLEX	PLEX is performed according to the respective site's standard procedure for desensitization.
DRUG	IVIg	IVIg prepared from a pool of immunoglobulins from the plasma of thousands of healthy donors is administered in accordance with respective site's standard procedure for desensitization.
DRUG	Anti-CD20 antibodies	Rituximab and other anti-CD20 according to the respective site's standard procedure for desensitization.
DRUG	Eculizumab	Eculizumab according to the respective site's standard procedure for desensitization.
OTHER	Remain on wait list	Remain on wait list for a more compatible organ offer if desentization with institutional protocol is not appropriate

Timeline

• Start date: 2021-10-14
• Primary completion: 2025-06-20
• Completion: 2025-06-20
• First posted: 2021-06-22
• Last updated: 2025-07-16

Locations

25 sites across 1 country: United States

Regulatory

• FDA-regulated drug study