Imlifidase Prior to Kidney Transplant in Highly Sensitised Children

Phase 2

Recruiting

• Conditions: Kidney Transplantation in Highly Sensitized Patients
• Interventions: Drug: Imlifidase

• Registration Number: NCT05753930
• Lead Sponsor: Hansa Biopharma AB

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.

Study Timeline

• Study First Submitted: 2023-02-23
• Study First Submitted QC: 2023-02-23
• Study First Posted: 2023-03-03
• Study Start: 2023-06-02
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-06
• Primary Completion: 2027-02-28
• Study Completion: 2031-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment	From start of imlifidase administration to 24 hours	Immunoglobulins (IgG) including donor specific antibodies (DSAs) are rapidly and efficiently cleaved by imlifidase. A conversion of a positive to a negative XM will enable transplantation.

Secondary Outcome Measures

Name	Time	Method
Renal function up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR)	From pre-dose imlifidase up to 5 years	eGFR is a measure of kidney function. Reduced kidney function is characterised by a decreased eGFR value.
Renal function up to 5 years after transplantation as assessed by serum/plasma cystatin C levels	From pre-dose imlifidase up to 5 years	Cystatin C is a measure of kidney function. Reduced kidney function is characterised by an increased value.
Proportion of patients with biopsy- and serology (DSA)-confirmed AMR up to 5 years after transplantation	From transplantation up to 5 years	Banff scores (Loupy et al. 2020) will be used for biopsy evaluation.
Proportion of patients with biopsy confirmed cell-mediated rejection (CMR) up to 5 years after transplantation	From transplantation up to 5 years	Banff scores (Loupy et al. 2020) will be used for biopsy evaluation.
Renal function up to 5 years after transplantation as assessed by proteinuria	From pre-dose imlifidase up to 5 years	Proteinuria (protein/creatinine ratio in urine) is a measure of kidney function. Reduced kidney function is characterised by an increased value.
DSA levels up to 5 years after transplantation	From pre-dose imlifidase up to 5 years	Donor specific antibodies (DSAs) are antibodies in the recipient directed against the transplanted organ.
Graft survival (death censored) up to 5 year after transplantation	From 6 months up to 5 years
Graft failure-free survival up to 5 years after transplantation	From 6 months up to 5 years
Patient survival up to 5 years after transplantation	From 6 months up to 5 years
Proportion of patients with dialysis dependency up to 5 years after transplantation	From 6 months up to 5 years
Imlifidase Pharmacokinetics (AUC)	From pre-dose imlifidase up to Day 15	AUC = Area under the imlifidase plasma concentration versus time curve.
Renal function up to 5 years after transplantation as assessed by serum/plasma creatinine levels	From pre-dose imlifidase up to 5 years	Creatinine is a measure of kidney function. Reduced kidney function is characterised by an increased value.
Frequency of delayed graft function (DGF)	From transplantation up 7 days after transplantation	DGF is defined as 'Need for dialysis within 7 days of transplantation' in "Delayed graft function in kidney transplantation: developing drugs for prevention, guidance for industry", FDA 2019.; Frequency of patients having DGF in accordance with this definition will be presented.
Length of DGF	From transplantation up 7 days after transplantation	DGF is defined as 'Need for dialysis within 7 days of transplantation' in "Delayed graft function in kidney transplantation: developing drugs for prevention, guidance for industry", FDA 2019.; The duration of DGFs in accordance with this definition will be presented.
Imlifidase Pharmacokinetics (Cmax)	From pre-dose imlifidase up to Day 15	Cmax = Maximum observed plasma concentration of imlifidase following dosing.
Imlifidase Pharmacokinetics (t1/2)	From pre-dose imlifidase up to Day 15	t1/2 = Terminal half-life of imlifidase.
Imlifidase Pharmacokinetics (CL)	From pre-dose imlifidase up to Day 15	CL = Clearance of imlifidase.
Immunogenicity profile of imlifidase up to 5 years after imlifidase treatment	From pre-dose imlifidase up to 5 years	Immunogenicity is assessed as serum concentration of anti-imlifidase IgG (ADA).
Imlifidase Pharmacokinetics (tmax)	From pre-dose imlifidase up to Day 15	tmax = Time point for maximum observed plasma concentration of imlifidase following dosing
Imlifidase Pharmacodynamic (PD) profile up to 9 days after imlifidase treatment	From pre-dose imlifidase up to Day 10	PD is assessed as serum concentrations of intact IgG and its fractions following infusion.
Imlifidase Pharmacokinetics (Vz)	From pre-dose imlifidase up to Day 15	Vz = Volume of distribution during the elimination phase

Trial Locations

Locations (4)

HUS, Helsinki University Hospital; 🇫🇮 Helsinki, Finland

Robert Debre University Hospital; 🇫🇷 Paris, France

Hospital Unviersitari Vall d'Hebron, Nefrología Pediátrica; 🇪🇸 Barcelona, Spain

Karolinska University Hospital; 🇸🇪 Huddinge, Stockholm, Sweden