Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes)

Stanley C. Jordan, Christophe Legendre, Niraj M. Desai, Tomas Lorant, Mats Bengtsson, Bonnie E. Lonze, Ashley A. Vo, Anna Runström, Lena Laxmyr, Kristoffer Sjöholm, Åsa Schiött, Elisabeth Sonesson, Kathryn Wood, Lena Winstedt, Christian Kjellman, Robert A. Montgomery

Research output: Contribution to journalArticlepeer-review


Background. Highly HLA sensitized patients have limited access to life-saving kidney transplantation because of a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney. Methods. This open-label, single-Arm, phase 2 trial conducted at 5 transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 h. Secondary endpoints included postimlifidase donor-specific antibody levels compared with predose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile. Results. Of the transplanted patients, 89.5% demonstrated conversion of baseline positive crossmatch to negative within 24 h after imlifidase treatment. Donor-specific antibodies most often rebounded 3-14 d postimlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 mo. With this, 38.9% had early biopsy proven antibody-mediated rejection with onset 2-19 d posttransplantation. Serum IgG levels began to normalize after ∼3-7 d posttransplantation. Antidrug antibody levels were consistent with previous studies. Seven adverse events in 6 patients were classified as possibly or probably related to treatment and were mild-moderate in severity. Conclusions. Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median calculated panel-reactive antibody of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 mo.

Original languageEnglish (US)
Pages (from-to)1808-1817
Number of pages10
Issue number8
StatePublished - Aug 1 2021

ASJC Scopus subject areas

  • Transplantation


Dive into the research topics of 'Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes)'. Together they form a unique fingerprint.

Cite this