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

NCT ID: NCT03897205

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2022-11-16

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.

Detailed Description

Antibodies to human leukocyte antigens (HLAs) have a strong correlation with allograft injury and loss. Treatment with imlifidase, PE and immunoabsorption (IA) all aim to reduce antibody levels.

This study compared the reduction in DSA levels after treatment with imlifidase and PE in patients diagnosed with active or chronic active AMR (according to Banff 2017 or Banff 2019 criteria) having at least a 25% rise in serum creatinine compared with last measurement prior to the AMR. (Patients with delayed graft function and AMR within 10 days after kidney transplantation could be included regardless of serum creatinine level.) Eligible patients were randomized to either 1 dose of imlifidase (0.25 mg/kg) or 5-10 sessions of PEs (IA could replace PE at the discretion of the investigator).

All patients received pulse methylprednisolone Day 1 to Day 3, followed by a tapering schedule with prednisolone/prednisone. Patients randomised to imlifidase received their first dose of methylprednisolone before imlifidase was administered. The patients did also receive high dose intravenous immunoglobulin (IVIg) 3 days after imlifidase treatment or directly after the last PE. In addition a single dose of rituximab was given 5 days after completed IVIg infusion.

Conditions

Kidney Transplant Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imlifidase

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

Group Type: EXPERIMENTAL

Imlifidase

Intervention Type: DRUG

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

Plasma Exchange

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.

Group Type: ACTIVE_COMPARATOR

Plasma Exchange

Intervention Type: 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.

Interventions

Imlifidase

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

Intervention Type: DRUG

Plasma Exchange

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.

Intervention Type: OTHER

Other Intervention Names

HMED-IdeS, IdeS, IgG endopeptidase

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent obtained before any study-related procedures

2. Willingness and ability to comply with the protocol

3. Male and/or female donor kidney recipients age ≥18 years at the time of screening

4. Presence of DSA(s)

5. Meet the Banff 2017 criteria for active or chronic active AMR

6. 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

7. 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

8. 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

Exclusion Criteria

1. Previous treatment with imlifidase

2. Previous high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion

3. Lactating or pregnant females

4. Significantly abnormal general serum screening lab results judged inappropriate for inclusion in the study by the investigator

5. Intake of other investigational drugs within 5 half-lives (or similar) of the product prior to inclusion

6. Clinically relevant active infection(s) as judged by the investigator

7. 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

8. Known allergy/sensitivity to imlifidase, IVIg and/or rituximab and the respective excipients

9. Patient unable to tolerate treatment with plasmapheresis or immunoadsorption, as judged by the investigator

10. Unsuitable to participate in the study for any other reason as judged by the investigator

11. Positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection

12. Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hansa Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Operations

Role: STUDY_DIRECTOR

Hansa Biopharma AB

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Brigham and Women Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

New York University Grossman School of Medicine

New York, New York, United States

The Royal Melbourne Hospital

Melbourne, Victoria, Australia

Royal Adelaide Hospital

Adelaide, , Australia

Royal Prince Alfred Hospital

Sydney, , Australia

Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie MUW

Vienna, , Austria

Hôpital Pellegrin

Bordeaux, , France

CHU Grenoble Alpes - Néphrologie, dialyse et transplantation

Grenoble, , France

Hôpital Saint-Louis. Service de Néphrologie et Transplantation

Paris, , France

Hôpital Necker - Service de Néphrologie - Transplantation

Paris, , France

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

Berlin, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Countries

United States; Australia; Austria; France; Germany

References

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.

Reference Type: DERIVED

PMID: 39023092 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000022-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16-HMedIdeS-12

Identifier Type: -

Identifier Source: org_study_id