NCT04935177

Brief 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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
64

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Oct 2021

Typical duration for phase_3

Geographic Reach
1 country

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 14, 2021

Completed
8 days until next milestone

First Posted

Study publicly available on registry

June 22, 2021

Completed
4 months until next milestone

Study Start

First participant enrolled

October 14, 2021

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 20, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 20, 2025

Completed
Last Updated

April 30, 2026

Status Verified

April 1, 2026

Enrollment Period

3.7 years

First QC Date

June 14, 2021

Last Update Submit

April 21, 2026

Conditions

Keywords

DesensitizationHighly sensitizedPositive crossmatchUnlikely to be transplantedRenal transplantationDeceased donor

Outcome Measures

Primary Outcomes (1)

  • Mean estimated glomerular filtration rate (eGFR) at 12 months

    eGFR is a measure of kidney function and will be compared between treatment arms. eGFR will be calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is 90 mL/min/1.73m2. Kidney disease is characterised by a decreased eGFR value. For randomized patients who do not undergo transplantation, lose their graft or die before 12 months, eGFR will be set to zero, consistent with kidney failure.

    12 months after randomization

Secondary Outcomes (1)

  • Patient survival at 12 months

    12 months after randomization

Other Outcomes (21)

  • Frequency of dialysis dependency at 12 months

    12 months after randomization

  • Graft failure-free survival at 12 months

    12 months after randomization

  • Graft survival at 12 months

    12 months after randomization

  • +18 more other outcomes

Study Arms (2)

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 generally 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.

Drug: Imlifidase

Best available treatment

OTHER

Institution-specific desensitization protocol (i.e. any combination of plasma exchange (PLEX), intravenous IVIg, anti-CD20 antibody, and eculizumab) where appropriate OR remain on wait list for a more compatible organ offer

Procedure: PLEXDrug: IVIgDrug: Anti-CD20 antibodiesDrug: EculizumabOther: Remain on wait list

Interventions

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
PLEXPROCEDURE

PLEX is performed according to the respective site's standard procedure for desensitization.

Also known as: Plasma exchange, PE
Best available treatment
IVIgDRUG

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.

Also known as: Intravenous immunoglobulin
Best available treatment

Rituximab and other anti-CD20 according to the respective site's standard procedure for desensitization.

Also known as: Rituximab
Best available treatment

Eculizumab according to the respective site's standard procedure for desensitization.

Also known as: Soliris
Best available treatment

Remain on wait list for a more compatible organ offer if desentization with institutional protocol is not appropriate

Best available treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Signed Informed Consent obtained before any trial-related procedures
  • Male or female age 18-70 years at the time of screening
  • Chronic kidney disease (CKD) stage 5, highly sensitized as evaluated by standard selection criteria, and active on the OPTN waiting list for a DD kidney transplant
  • Original calculated panel reactive antibody (cPRA) ≥99.9%
  • Virtual crossmatch (vXM), predictive of a positive crossmatch to an available deceased donor (DD)
  • Willingness and ability to comply with the protocol
  • Willingness to participate in the planned 4-year extension trial

You may not qualify if:

  • High dose IVIg (2 g/kg) treatment within 28 days prior to imlifidase treatment
  • Previous treatment with imlifidase
  • Breast feeding or pregnancy
  • Women of child-bearing potential not willing or able to practice FDA-approved forms of contraception, or abstinence. Two medically acceptable methods of highly effective contraception must be used for the duration of the study (e.g. oral, transdermal, intravaginal, injectable or implantable contraceptive; intrauterine device; intrauterine hormone-releasing system; vasectomized partner; bilateral tubal occlusion; or double barrier method). For a woman to be considered postmenopausal this ascertainment must be made according to medical records and clinical history and may be aided by measurement of elevated postmenopausal serum gonadotropin levels (FSH).
  • ABO blood group incompatible transplantations (A2 or A2B kidneys will not be accepted for B recipients)
  • Positive serology for human immunodeficiency virus (HIV)
  • Clinical signs of hepatitis B virus (HBV) or hepatitis C virus (HCV) infections
  • Clinical signs of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infections
  • Positive test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (according to local hospital routines)
  • Active tuberculosis
  • Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure ≥grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent chronic obstructive pulmonary disease (COPD)
  • Any condition that in the view of the Investigator precludes transplantation
  • History of a proven hypercoagulable condition
  • Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
  • Intake of investigational drugs within 5 half-lives of the drug or 3 months, whichever is the longest
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

University of Alabama at Birmingham (UAB) Hospital

Birmingham, Alabama, 35249, United States

Location

Banner Health - University Medical Center - Phoenix

Phoenix, Arizona, 85006, United States

Location

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

Keck Hospital of University of Southern California (USC)

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sutter Health - California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California San Francisco (UCSF) Medical Center

San Francisco, California, 94143-0780, United States

Location

Georgetown Transplant Institute

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

New York University (NYU) Langone Transplant Institute, NYU Langone Health

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032, United States

Location

New York-Presbyterian - Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Hospital of the University of Pennsylvania, Penn Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Methodist Hospital Specialty and Transplant

San Antonio, Texas, 78229, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Interventions

Mac-1-like protein, StreptococcusPlasma ExchangeImmunoglobulins, IntravenousRituximabeculizumab

Intervention Hierarchy (Ancestors)

Blood TransfusionBiological TherapyTherapeuticsPlasmapheresisBlood Component RemovalSorption DetoxificationExtracorporeal CirculationSurgical Procedures, OperativeImmunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsAntibodies, Monoclonal, Murine-DerivedAntibodies, Monoclonal

Study Officials

  • Clinical Operations

    Hansa Biopharma AB

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Open-label, controlled and randomized
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 14, 2021

First Posted

June 22, 2021

Study Start

October 14, 2021

Primary Completion

June 20, 2025

Study Completion

June 20, 2025

Last Updated

April 30, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations