An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients

NCT03897205 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16-HMedIdeS-122018-000022-66
• Study Type: interventional
• Target: 30
• Locations: 4 countries
• Sites: 11

Brief Summary

The purpose of this study was to investigate how efficiently the study medication imlifidase reduces the amount of donor specific antibodies (DSA) in comparison with plasma exchange (PE) therapy, in patients who have had an active or chronic active antibody mediated rejection (AMR) after being kidney transplanted. The purpose was also to investigate and compare safety for these two treatments.

Conditions

Kidney Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment

  Maximum reduction (%) in the sum of DSA at any time point during the 5 days following the start of treatment. Only DSA with ≥1000 mean fluorescence intensity (MFI) at pre-treatment were included in the calculations. Clarification: The higher the maximum reduction percentage the lower the remaining DSA level.

  Start of treatment until 5 days following start of treatment

Secondary Outcomes (18)

• Reduction in DSA Levels After Treatment

  Screening until Day 180

• Estimated Glomerular Filtration Rate (eGFR) Levels

  Screening until Day 180

• Urine Albumine/Creatinine Ratio

  Pre-dose until Day 180

• Number of Patients With Graft Loss Within 180 Days of Treatment

  Screening until Day 180

• Number of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180

  Day 180

Study Arms (2)

Imlifidase

EXPERIMENTAL

Subjects randomized to imlifidase treatment received one intravenous dose of imlifidase, 0.25 mg/kg, administered over 15 minutes.

Drug: Imlifidase

Plasma Exchange

ACTIVE COMPARATOR

Subjects randomized to plasma exchange (PE) treatment received 5-10 sessions of PE, as judged by the investigator. Immunoadsorption (IA) could replace PE, at the discretion of the investigator.

Other: Plasma Exchange

Interventions

Imlifidase DRUG

Imlifidase is an immunoglobulin G (IgG) degrading enzyme of Streptococcus pyrogenes that cleaves all 4 human subclasses of IgG with strict specificity.

Also known as: HMED-IdeS, IdeS, IgG endopeptidase

Imlifidase

Plasma Exchange OTHER

The subject's plasma is removed and discarded and the subject receives replacement donor plasma, albumin, or a combination of albumin and saline. IA may be used instead of PE to the discretion of the investigator. IA is achieved by passing a subject's plasma over columns that bind immunoglobulins and then the plasma is passed back to the subject.

Plasma Exchange

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent obtained before any study-related procedures
• Willingness and ability to comply with the protocol
• Male and/or female donor kidney recipients age ≥18 years at the time of screening
• Presence of DSA(s)
• Meet the Banff 2017 criteria for active or chronic active AMR
• At least 25% rise in serum creatinine compared to last individual value taken prior to the AMR. Patients with delayed graft function and AMR within 10 days after transplant (confirmed by kidney biopsy) can be included regardless of serum creatinine level
• Women of child-bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
• Men willing to use double-barrier contraception from the first day of treatment until at least 2 months after the dose of imlifidase, if not abstinent

You may not qualify if:

• Previous treatment with imlifidase
• Lactating or pregnant females
• Clinically relevant active infection(s) as judged by the investigator
• Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study such as severe immune deficiency and severe cardiac insufficiency \[New York Heart Association (NYHA) Class IV\] or severe uncontrolled heart disease
• Known allergy/sensitivity to imlifidase, IVIg and/or rituximab and the respective excipients
• Patient unable to tolerate treatment with plasmapheresis or immunoadsorption, as judged by the investigator
• Unsuitable to participate in the study for any other reason as judged by the investigator
• Positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection
• Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (14)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Brigham and Women Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

New York University Grossman School of Medicine

New York, New York, 10016, United States

Location

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Royal Adelaide Hospital

Adelaide, 5000, Australia

Location

Royal Prince Alfred Hospital

Sydney, Australia

Location

Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie MUW

Vienna, 1090, Austria

Location

Hôpital Pellegrin

Bordeaux, 33076, France

Location

CHU Grenoble Alpes - Néphrologie, dialyse et transplantation

Grenoble, 38043, France

Location

Hôpital Saint-Louis. Service de Néphrologie et Transplantation

Paris, 75475, France

Location

Hôpital Necker - Service de Néphrologie - Transplantation

Paris, 75743, France

Location

Charité-Universitätsmedizin. Dept. of Nephrology and Medical Intensive Care

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Related Publications (1)

• Halleck F, Bohmig GA, Couzi L, Rostaing L, Einecke G, Lefaucheur C, Legendre C, Montgomery R, Hughes P, Chandraker A, Wyburn K, Halloran P, Maldonado AQ, Sjoholm K, Runstrom A, Lefevre P, Tollemar J, Jordan S. A Randomized Trial Comparing Imlifidase to Plasmapheresis in Kidney Transplant Recipients With Antibody-Mediated Rejection. Clin Transplant. 2024 Jul;38(7):e15383. doi: 10.1111/ctr.15383.

  PMID: 39023092 DERIVED

MeSH Terms

Interventions

Mac-1-like protein, Streptococcus; Plasma Exchange

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Results Point of Contact

• Title: Vice President Research and Development
• Organization: Hansa Biopharma AB

info@hansabiopharma.com

+4646165670

Study Officials

• Clinical Operations

  Hansa Biopharma AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 1, 2019
• Study Start: April 30, 2019
• Primary Completion: May 28, 2022
• Study Completion: November 16, 2022
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); DE (2); US (4); AU (1)