Imlifidase Prior to Kidney Transplant in Highly Sensitised Children

NCT ID: NCT05753930

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-02
• Study Completion Date: 2031-08-31

Brief Summary

The goal of this clinical trial is to learn about the efficacy and safety of imlifidase in highly sensitized paediatric patients, 1-17 years old, with end stage renal disease (ESRD).

The main questions it aims to answer are:

• Does imlifidase treatment result in crossmatch conversion that enables transplantation?
• How is the function of the transplanted kidney?

The participants will be hospitalised in accordance with the normal routines for transplanted patients. The patients will receive medication to prevent rejection of the donor kidney, and because such treatment make the body more vulnerable medications to prevent infections.

Detailed Description

After being informed about the study and potential risks, all patients giving written informed consent will undergo pre-screening to determine eligibility for study entry.

The trial will include highly sensitised ESRD paediatric patients (1-17 years). The patients have previously undergone desensitization unsuccessfully or have an anti-HLA antibody status deemed too difficult to make a successful desensitization using other experimental methods.

A screening visit will take place when an organ offer has been placed for a final check of the patients' eligibility for study participation.

All patients included in the trial will be desensitized with imlifidase to convert the positive XM to negative and then transplanted with either a kidney from a deceased donor (DD) or a living donor (LD).

Patients will be hospitalised in accordance with the normal routines for transplanted patients at each clinic.

Following transplantation, the patients will receive induction therapies, rejection prophylaxis, and maintenance immunosuppressive therapies.

The patients will be closely monitored for any signs of antibody-mediated rejections (AMRs).

The duration of the interventional trial period after an organ has been offered will be 6 months for each patient. The trial includes a follow-up part to collect long-term efficacy and safety data up to 5 years after the transplantation.

Conditions

Kidney Transplantation in Highly Sensitized Patients

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imlifidase

Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes within 24 hours prior to transplantation.

Group Type: EXPERIMENTAL

Imlifidase

Intervention Type: 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.

Interventions

Imlifidase

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.

Intervention Type: DRUG

Other Intervention Names

IdeS, HMED-IdeS

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent obtained from patient/parent/legal guardian/independent witness (depending on patient's age) before any trial-related procedures

2. Highly sensitised patient with panel reactive antibodies (PRA) ≥80%

3. Male or female patient between the age of 1 to 17 years (up to the day before the 18th birthday) at the time of screening

4. Patient with end-stage renal disease (ESRD) and waiting for a renal transplant from a living or deceased donor

5. Patient must be transplantable (including size mismatch) at the time of obtaining informed consent for trial participation

6. Patients who have previously undergone desensitisation unsuccessfully with plasmapheresis/IVIg/anti-CD20 or have an anti-HLA antibody status deemed too difficult to make a successful desensitisation (judgement based on physicians' previous experience with similar patients)

7. Positive crossmatch (XM) test determined by flow cytometry crossmatch (FCXM) and/or complement-dependent cytotoxicity crossmatch (CDCXM) tests against the donor. For the DD patients, 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.

8. Willingness and ability to comply with the protocol as judged by the investigator

Exclusion Criteria

1. Previous treatment with imlifidase

2. IVIg treatment within 28 days prior to imlifidase treatment

3. Desensitisation treatment(s) within 1 month prior to the current transplantation

4. Hypersensitivity to the active substance (imlifidase) or to any of the excipients and to other immunosuppressive drugs specified in the protocol

5. Ongoing serious infections

6. Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP

7. At the time of transplantation: severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease, active peripheral vascular disease, proven hypercoagulable conditions/events or oxygen dependent respiratory disease

8. Malignancy within 3 years prior to transplantation

9. ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients)

10. Any other reason that, in the view of the investigator, precludes transplantation

11. Breast feeding or pregnancy, if applicable

12. Woman of fertile age and sexually active without adequate contraceptive measures to avoid pregnancy during the interventional trial period (i.e. up to 6 months after transplantation)

13. Suspicion of Covid-19 infection or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test

14. Positive serology for human immunodeficiency virus (HIV)

15. Clinical signs of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), or Epstein Barr virus (EBV) infection

16. Donor with positive serology for HIV, HBV, HCV, CMV or EBV to a patient with negative serology (mismatch serology)

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

18. Tuberculosis or history of tuberculosis

19. Use of other investigational agents within 5 terminal elimination half-lives prior to the transplantation

20. Contemporaneous participation in medical device studies

21. Known mental incapacity or language barriers precluding patients'/parents'/legal guardians' adequate understanding of the informed consent information and the trial activities

22. Inability by the judgement of the investigator to participate in the trial for any other reason

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 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

HUS, Helsinki University Hospital

Helsinki, , Finland

Site Status: RECRUITING

Robert Debre University Hospital

Paris, , France

Site Status: RECRUITING

Hospital Unviersitari Vall d'Hebron, Nefrología Pediátrica

Barcelona, , Spain

Site Status: RECRUITING

Karolinska University Hospital

Huddinge, Stockholm County, Sweden

Site Status: RECRUITING

Countries

Finland; France; Spain; Sweden

Central Contacts

Central Contact

Role: CONTACT

clinicalstudyinfo@hansabiopharma.com

+46 46 16 56 70

Facility Contacts

T Jahnukainen, MD

Role: primary

Timo.Jahnukainen@hus.fi

Julien Hogan, Professor

Role: primary

julien.hogan2@aphp.fr

Gema Ariceta, MD

Role: primary

gema.ariceta@vallhebron.cat

L Wennberg, MD

Role: primary

Lars.Wennberg@regionstockholm.se

References

Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen JP, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel M. The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection. Am J Transplant. 2020 Sep;20(9):2318-2331. doi: 10.1111/ajt.15898. Epub 2020 May 28.

Reference Type: BACKGROUND

PMID: 32463180 (View on PubMed)

Other Identifiers

2022-500230-28-00

Identifier Type: OTHER

Identifier Source: secondary_id

20-HMedIdes-21

Identifier Type: -

Identifier Source: org_study_id