Desensitisation with imlifidase prior to kidney transplant in highly sensitised children

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hansa Biopharma AB

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

2 Jun 2023 → ongoing

Decision date (initial)

2023-02-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy, Pharmacodynamic

To evaluate crossmatch conversion with imlifidase treatment

Secondary objectives 10

1. To evaluate renal function
2. To evaluate human leukocyte antigen (HLA)/donor specific antibody (DSA) levels
3. To evaluate graft survival
4. To evaluate patient survival
5. To evaluate delayed graft function (DGF)
6. To evaluate pharmacokinetic (PK) profile of imlifidase
7. To evaluate pharmacodynamic (PD) profile of imlifidase
8. To evaluate immunogenicity profile of imlifidase (anti-drug antibodies [ADAs])
9. To evaluate proportion of biopsy- and serology-confirmed antibody-mediated reactions (AMRs) and biopsy confirmed cell-mediated rejections (CMRs)
10. To evaluate safety and tolerability of imlifidase treatment

Conditions and MedDRA coding

Highly sensitised paediatric patients with a positive crossmatch against a living or deceased donor kidney.

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002183-PIP01-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 test determined by FCXM and/or CDCXM tests against the donor. For the DD patients, if physical crossmatch tests are not practically possible due to lack of time, patients may be included on a vXM predictive of a positive crossmatch test.
8. Willingness and ability to comply with the protocol as judged by the investigator

Exclusion criteria 23

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 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. Any circumstance (such as persons deprived of liberty or persons being reliant on care and for that reason are accommodated in residential care) that could inappropriately influence a patients (or parents’/legal guardians’) decision to participate in the trial.
23. Inability by the judgement of the investigator to participate in the trial for any other reason

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment

Secondary endpoints 14

1. Renal function at several time points up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR), serum/plasma creatinine and cystatin C levels and proteinuria (protein/creatinine ratio in urine)
2. DSA levels at several time points between pre-dose imlifidase up to 5 years after transplantation
3. Graft survival, death censored, up to 5 years after transplantation
4. Graft failure-free survival up to 5 years after transplantation
5. Patient survival up to 5 years after transplantation
6. Frequency and length of DGF
7. Dialysis dependency up to 5 years after transplantation
8. Imlifidase PK profile up to 14 days after imlifidase treatment
9. Imlifidase PD profile up to 9 days after imlifidase treatment
10. Immunogenicity profile of imlifidase by measuring ADAs up to 5 years after imlifidase treatment
11. Proportion of patients with biopsy- and serology (DSA)-confirmed AMR and biopsy confirmed CMRs up to 5 years after transplantation
12. Safety parameters (adverse events [AEs]/serious adverse events [SAEs], clinical laboratory tests, vital signs and electrocardiogram [ECG]) up to 5 years after transplantation
13. Safety assessed as proportion of patients with infusion related reactions within 48 hours of imlifidase infusion
14. Safety assessed as proportion of patients with severe or serious infections within 30 days after imlifidase treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hansa Biopharma AB

Sponsor organisation

Hansa Biopharma AB

Address

P.O. Box 785

City

Lund

Postcode

220 07

Country

Sweden

Scientific contact point

Organisation

Hansa Biopharma AB

Contact name

Clinical contact information

Public contact point

Organisation

Hansa Biopharma AB

Contact name

Clinical contact information

Third parties 6

Locations

4 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications