Efficacy and Safety in Imlifidase Desensitized Kidney Tx Patients, Including Two Non-Comparative Reference Cohorts

NCT05369975 | Completed Phase 3 DMC

• 2 other identifiers: 20-HMedIdeS-192021-002640-70
• Study Type: interventional
• Target: 113
• Locations: 11 countries
• Sites: 22

Brief Summary

An open-label post authorization efficacy and safety study evaluating graft failure-free survival at 1-year in highly sensitized end-stage renal disease (ESRD) patients with positive crossmatch (XM) against a deceased donor prior to desensitized with imlifidase and subsequent kidney transplantation. Two non-comparative reference cohorts are included to assess the impact of differences in post-transplantation management and outcome in less sensitized patients.

Conditions

Kidney Transplantation in Highly Sensitized Patients

Keywords

Desensitization; Highly sensitized; Positive crossmatch; Unlikely to be transplanted; Renal transplantation; Kidney transplantation; Deceased donor; End-Stage Renal Disease; ESRD

Outcome Measures

Primary Outcomes (1)

• Graft failure-free survival 1 year after transplantation following imlifidase treatment

  Graft failure is defined as permanent return to dialysis for at least 6 weeks, re-transplantation, or nephrectomy. Patients who die from any cause will be considered as having graft failure. If a patient is not undergoing transplantation following imlifidase treatment the patient will be censored at time zero when constructing Kaplan-Meier curves for graft failure-free survival. The 1-year graft failure-free survival rates will be extracted from Kaplan-Meier curves. Time from enrolment to the first of death or graft failure will be used as time variable.

  12 months after transplantation

Secondary Outcomes (21)

• Graft failure-free survival 1 year after transplantation in non-comparative concurrent reference cohort

  12 months after transplantation

• Renal function up to 1 year after transplantation

  Screening, pre-imlifidase, 24, 48 and 72 hours, Days 5, 6, 8, 10 and 15, at 1, 3 and 6 months and at 1 year

• Patient survival at 1 year after transplantation

  12 months after transplantation

• Graft survival at 1 year after transplantation

  12 months after transplantation

• Proportion of patients with conversion of a positive XM test to negative within 24 hours after imlifidase treatment

  Pre-imlifidase, 2, 4 and 24 hours post-imlifidase.

Study Arms (3)

Imlifidase

EXPERIMENTAL

Imlifidase, is provided as a freeze-dried powder for concentrate for solution for infusion, 11 mg per vial. After reconstitution with sterile water for injection, the concentrate contains 10 mg/mL imlifidase. Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes within 24 hours prior to transplantation. A second dose of 0.25 mg/kg may be given if the first imlifidase dose is considered not to have had sufficient effect. The second dose can be administered within 24 hours after the first dose.

Drug: Imlifidase

Non-Comparative Concurrent Reference Cohort

OTHER

Patients in the non-comparative prospective concurrent reference cohort (with any grade of sensitization and negative XM) will receive medications, both pre- and post-transplant, in accordance with each clinic's routine for kidney transplanted patients.

Other: Normal Transplantation Routine

Non-Comparative Historical Reference Cohort

OTHER

Patients in the non-comparative historical reference cohort (with less sensitization and negative XM) randomly selected from the CTS registry have been transplanted and treated in accordance with standard-of-care for kidney transplanted patients. Patients transplanted in 2010 and onwards will be selected to optimize the probability that these patients will have received about the same maintenance immunosuppressive treatment as the patients in the current trial will receive.

Other: Normal Transplantation Routine

Interventions

Imlifidase DRUG

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.

Also known as: IdeS, HMED-IdeS

Imlifidase

Normal Transplantation Routine OTHER

Transplantation and pre- and post-transplantation therapies in accordance with the clinic's normal transplantation routine.

Non-Comparative Concurrent Reference Cohort; Non-Comparative Historical Reference Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient aged 18-75 years
• ABO-compatible deceased donor aged 10-70 years
• ESRD active on the renal transplant waiting list of a kidney allocation system at the time of screening
• High sensitization with the highest unmet medical need unlikely to be transplanted under the available kidney allocation system including prioritisation programmes for highly sensitized patients
• Known DSA against an available deceased donor
• Positive crossmatch test determined by complement-dependent cytotoxicity crossmatch (CDCXM) and/or flow cytometric crossmatch (FCXM) against an available deceased donor. If physical XM tests are not practically possible due to lack of time, patients may be included on a virtual crossmatch (vXM) predictive of a positive XM test.
• Signed Informed Consent obtained before any trial-related procedures
• Willingness and ability to comply with the protocol
• Active on the renal transplant waiting list at a participating trial site at the time of screening
• An acceptable kidney transplant from a deceased donor
• Signed Informed Consent obtained before any trial related procedures
• Willingness and ability to comply with the protocol
• ESRD with a kidney transplant from a deceased donor
• Being transplanted in Europe after 01-Jan-2010 and included in the CTS registry
• Panel reactive antibodies (PRA) ≥ 50% (CDC T- or B-cell PRA, calculated panel reactive antibodies (cPRA), or virtual panel reactive antibodies (vPRA))

You may not qualify if:

• Use of investigational agents within 5 terminal elimination half-lives prior to the transplantation
• Malignancy within 5 years prior to transplantation
• Positive serology for human immunodeficiency virus (HIV)
• Clinically relevant active infection(s) as judged by the investigator
• Contemporaneous participation in medical device studies
• Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities
• Inability by the judgement of the investigator to participate in the trial for any other reason
• Previous treatment with imlifidase
• Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment
• Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test
• Breast feeding or pregnancy
• Hypersensitivity to the active substance (imlifidase) or to any of the excipients
• Ongoing serious infections
• Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
• Severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent respiratory disease

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (22)

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

UZ Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Institut klinicke a experimentalni mediciny (IKEM)

Prague, 140-21, Czechia

Location

Centre Hospitalier Universitaire (CHU) de Rouen - Hôpital de Bois-Guillaume

Bois-Guillaume, 76230, France

Location

CHU de Grenoble - Hôpital Michallon

La Tronche, 38700, France

Location

Hôpital Necker - Enfants Malades

Paris, 75015, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Klinikum rechts der Isar der Technische Universitaet Muenchen

Munich, 81675, Germany

Location

Azienda Ospedaliera di Padova

Padova, 35128, Italy

Location

Azienda Ospedaliero - Universitaria di Parma

Parma, 43100, Italy

Location

University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015 GD, Netherlands

Location

Department of Nephrology , Zaloška 7

Ljubljana, 1000, Slovenia

Location

Hospital Del Mar, Servicio de Nefrología

Barcelona, 08003, Spain

Location

Hospital Clínic de Barcelona, Unidad de Trasplante Renal

Barcelona, 08036, Spain

Location

Vall d'Hebron University Hospital (HUVH)

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Karolinska University Hospital

Huddinge, 141 57, Sweden

Location

Uppsala University Hospital

Uppsala, 751 85, Sweden

Location

St. James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

Location

Related Publications (1)

• Vo A, Ammerman N, Jordan SC. New Therapies for Highly Sensitized Patients on the Waiting List. Kidney360. 2024 Aug 1;5(8):1207-1225. doi: 10.34067/KID.0000000000000509. Epub 2024 Jul 12.

  PMID: 38995690 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Mac-1-like protein, Streptococcus

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Operations

  Hansa Biopharma AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, non-randomised trial in highly sensitized adult kidney transplant patients with positive XM against an available deceased donor. The rational for a non-randomised trial is that no other effective or approved desensitization protocol exists in deceased-donor kidney transplantation that would provide a suitable control. A non-comparative concurrent reference cohort from participating sites will be included to address differences in-site practice and experience. A non-comparative historical reference cohort from the CTS registry will be included to address the outcome in a less sensitized patient group.

Study Record Dates

• First Submitted: May 6, 2022
• First Posted: May 11, 2022
• Study Start: April 19, 2022
• Primary Completion: April 21, 2026
• Study Completion: April 21, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1); ES (4); AU (1); SE (2); NL (3); SL (1); IT (2); GB (2); FR (3); DE (2); BE (1)