Study in highly sensitised kidney transplant patients with a high degree of antibodies against the donor's kidney to see the efficacy and safety of imlifidase to temporarily remove the antibodies and enable the transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hansa Biopharma AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

19 Apr 2022 → 22 Apr 2026

Decision date (initial)

2024-09-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511810-18-00

EudraCT number

2021-002640-70

ClinicalTrials.gov

NCT05369975

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the 1-year graft failure-free survival in highly sensitised kidney transplant patients, pre-treated with imlifidase to turn a positive crossmatch against a deceased donor negative

Secondary objectives 29

1. To evaluate renal function up to 1 year after transplantation (imlifidase cohort)
2. To evaluate patient survival 1 year after transplantation (imlifidase cohort)
3. To evaluate graft survival 1 year after transplantation (imlifidase cohort)
4. To evaluate crossmatch conversion within 24 hours of imlifidase treatment (imlifidase cohort)
5. To evaluate HLA/DSA antibody levels up to 1 year after transplantation (imlifidase cohort)
6. To evaluate pharmacokinetic (PK) profile of imlifidase (imlifidase cohort)
7. To evaluate pharmacodynamic (PD) profile of imlifidase (imlifidase cohort)
8. To evaluate immunogenicity profile of imlifidase (anti-drug antibodies [ADAs]) (imlifidase cohort)
9. To evaluate delayed graft function (DGF) (imlifidase cohort)
10. To evaluate proportion of patients with biopsy- and serology-confirmed AntibodyMediated Rejections (AMRs) up to 1 year after transplantation (imlifidase cohort)
11. To evaluate proportion of patients with biopsy confirmed Cell-Mediated Rejections (CMRs) up to 1 year after transplantation (imlifidase cohort)
12. To evaluate safety of imlifidase treatment with regards to reported serious adverse events (SAEs) (imlifidase cohort)
13. To evaluate safety of imlifidase treatment with regards to infusion related reactions occurring within 48 hours of imlifidase infusion (imlifidase cohort)
14. To evaluate safety of imlifidase treatment with regards to severe or serious infections occurring within 30 days after transplantation (imlifidase cohort)
15. To evaluate health related quality of life (HRQoL) specifically patients’ life participation (imlifidase cohort)
16. To evaluate graft failure-free survival 1 year after transplantation (concurrent reference cohort)
17. To evaluate renal function up to 1 year after transplantation (concurrent reference cohort)
18. To evaluate patient survival 1 year after transplantation (concurrent reference cohort)
19. To evaluate graft survival 1 year after transplantation (concurrent reference cohort)
20. To evaluate DGF (concurrent reference cohort)
21. To evaluate proportion of patients with biopsy- and serology-confirmed AMRs up to 1 year after transplantation (concurrent reference cohort)
22. To evaluate proportion of patients with biopsy confirmed CMRs up to 1 year after transplantation (concurrent reference cohort)
23. To evaluate number of reported SAEs up to 1 year after transplantation (concurrent reference cohort)
24. To evaluate proportion of patients with severe or serious infections within 30 days after transplantation (concurrent reference cohort)
25. To evaluate health related quality of life (HRQoL) specifically patients’ life participation (concurrent reference cohort)
26. To evaluate graft survival 1 year after transplantation (historical reference cohort)
27. To evaluate renal function up to 1 year after transplantation (historical reference cohort)
28. To evaluate patient survival 1 year after transplantation (historical reference cohort)
29. To evaluate proportion of patients with rejection episodes during the first posttransplant year in patients with a functioning graft at the end of the first posttransplant year (historical reference cohort)

Conditions and MedDRA coding

End stage chronic kidney disease (CKD) patients who are highly sensitised and on the kidney transplant list awaiting a kidney transplant

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Male or female patient aged 18-75 years
2. ABO-compatible deceased donor aged 10-70 years
3. End-stage renal disease (ESRD) active on the renal transplant waiting list of a kidney allocation system at the time of screening (imlifidase patients)
4. High sensitisation with the highest unmet medical need unlikely to be transplanted under the available kidney allocation system including prioritisation programmes for highly sensitised patients (imlifidase patients)
5. Known DSA against an available deceased donor (imlifidase patients)
6. Positive crossmatch test (imlifidase patients)
7. Signed Informed Consent obtained before any trial-related procedures (imlifidase and concurrent reference patients)
8. Willingness and ability to comply with the protocol (imlifidase and concurrent reference patients)
9. Active on the renal transplant waiting list at a participating trial site at the time of screening (concurrent reference cohort patients)
10. An acceptable kidney transplant from a deceased donor (concurrent reference cohort patients)
11. End-stage renal disease with a kidney transplant from a deceased donor (historical reference cohort patients)
12. Being transplanted in Europe after 01-Jan-2010 and included in the CTS registry (historical reference cohort patients)
13. PRA ≥ 50% (CDC T or B cell PRA, cPRA, or virtual PRA [vPRA]) (historical reference cohort patients)
14. Maintenance immunosuppression (intention to treat) with calcineurin inhibitor, mycophenolate mofetil (MMF) and corticosteroids in combination (historical reference cohort patients)

Exclusion criteria 19

1. Previous treatment with imlifidase (imlifidase patients)
2. Female of childbearing potential, not willing to use effective contraception during the 3 weeks following treatment with imlifidase. In the context of this trial, 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 (imlifidase patients)
3. Use of investigational agents within 5 terminal elimination half-lives prior to the transplantation (imlifidase and concurrent reference cohort)
4. Any other reason that, in the view of the investigator, precludes transplantation (imlifidase patients)
5. Previous high dose IVIg treatment (2 g/kg) within 28 days prior to imlifidase treatment (imlifidase patients)
6. Suspicion of Covid-19 infection or positive SARS-CoV-2 test (imlifidase patients)
7. Breast feeding or pregnancy (imlifidase patients)
8. Hypersensitivity to the active substance (imlifidase) or to any of the excipients (imlifidase patients)
9. Ongoing serious infections (including HBV, HCV, CMV, EBV, tuberculosis) (imlifidase patients)
10. Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP (imlifidase patients)
11. Severe other condition requiring treatment and close monitoring e.g. cardiac failure ≥ grade 4 (New York Heart Association), unstable coronary disease or oxygen dependent respiratory disease (imlifidase patients)
12. Malignancy within 5 years prior to transplantation (imlifidase and concurrent reference cohort)
13. Positive serology for human immunodeficiency virus (HIV) (imlifidase and concurrent reference cohort)
14. Clinically relevant active infection(s) (including hepatitis B [HBV], hepatitis C [HCV], cytomegalovirus [CMV], Epstein Barr Virus [EBV], tuberculosis) as judged by the investigator (imlifidase and concurrent reference cohort)
15. Contemporaneous participation in medical device studies (imlifidase and concurrent reference cohort)
16. Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the trial activities (imlifidase and concurrent reference cohort)
17. Inability by the judgement of the investigator to participate in the trial for any other reason (imlifidase and concurrent reference cohort)
18. Patients treated with mTOR (mammalian target of rapamycin) inhibitors (historical reference cohort)
19. Patients treated with belatacept (historical reference cohort)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1-year graft failure-free survival in patients who have been kidney transplanted after imlifidase treatment

Secondary endpoints 29

1. Renal function at several time points between 24 hours and 2 weeks and at 1, 3 and 6 months and 1 year after transplantation as assessed by estimated glomerular filtration rate (eGFR) and serum/plasma creatinine levels (imlifidase cohort)
2. Patient survival at 1 year after transplantation (imlifidase cohort)
3. Graft survival at 1 year after transplantation (imlifidase cohort)
4. Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after imlifidase treatment
5. HLA/DSA antibody levels at several time points between pre-dose imlifidase and 2 weeks, and at 1, 3 and 6 months and 1 year after imlifidase treatment
6. Imlifidase PK up to 14 days after imlifidase treatment
7. Imlifidase PD up to 9 days after imlifidase treatment
8. ADAs up to 1 year after imlifidase treatment
9. Frequency of DGF (imlifidase cohort)
10. Proportion of patients with biopsy- and serology (DSA)-confirmed AMRs over 1 year (imlifidase cohort)
11. Proportion of patients with biopsy confirmed CMRs over 1 year (imlifidase cohort)
12. Safety over 1 year as measured by reported SAEs (imlifidase cohort)
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 transplantation (imlifidase cohort)
15. Change in patient-reported life participation, as measured by the PROMIS Social Health domain “Ability to participate in social roles & activities, PROMIS-SF-8a”, from baseline to 1 year after transplantation (imlifidase cohort)
16. Graft failure-free survival at 1 year after transplantation (concurrent reference cohort)
17. Renal function at 1, 3 and 6 months and 1 year after transplantation as assessed by eGFR and serum/plasma creatinine levels (concurrent reference cohort)
18. Patient survival at 1 year after transplantation (concurrent reference cohort)
19. Graft survival at 1 year after transplantation (concurrent reference cohort)
20. Frequency of DGF (concurrent reference cohort)
21. Proportion of patients with biopsy- and serology (DSA)-confirmed AMRs over 1 year (concurrent reference cohort)
22. Proportion of patients with biopsy confirmed CMRs over 1 year (concurrent reference cohort)
23. Safety over 1 year as measured by reported SAEs (concurrent reference cohort)
24. Safety assessed as proportion of patients with severe or serious infections within 30 days after transplantation (concurrent reference cohort)
25. Change in patient reported life participation, as measured by the PROMIS Social Health domain “Ability to participate in social roles & activities, PROMIS-SF-8a”, from baseline to 1 year after transplantation (concurrent reference cohort)
26. Graft survival at 1 year after transplantation (historical reference cohort)
27. Renal function at 3 and 6 months, and 1 year as measured by serum/plasma creatinine category (<130 µmol/L, 130-259 µmol/L, 260-400 µmol/L and >400 µmol/L) (eGFR only available in selected patients) (historical reference cohort)
28. Patient survival at 1 year after transplantation (historical reference cohort)
29. Proportion of patients with rejection episodes (AMRs and CMRs) during the first post-transplant year in patients with a functioning graft at the end of the first posttransplant year (historical reference cohort)

Investigational products

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

Test 1

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 11

Locations

10 EU/EEA countries · 20 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 72 files

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

Application history

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