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Imlifidase Prior to Kidney Transplant in Highly Sensitised Children

  • 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.

NCT_ID: NCT05753930

Clinical Trial Link

Brief Summaries

Sequence: 30856319
Description 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.

Studies

Study First Submitted Date 2023-02-23
Study First Posted Date 2023-03-03
Last Update Posted Date 2023-07-07
Start Month Year June 2, 2023
Primary Completion Month Year September 30, 2024
Verification Month Year July 2023
Verification Date 2023-07-31
Last Update Posted Date 2023-07-07

Detailed Descriptions

Sequence: 20782209
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.

Facilities

Sequence: 200605493
Status Recruiting
Name Hospital Unviersitari Vall d'Hebron, Nefrología Pediátrica
City Barcelona
Zip 08035
Country Spain

Facility Contacts

Sequence: 28184934
Facility Id 200605493
Contact Type primary
Name Gema Ariceta, MD
Email gema.ariceta@vallhebron.cat

Facility Investigators

Sequence: 18379032
Facility Id 200605493
Role Principal Investigator
Name Gema Ariceta, MD

Conditions

Sequence: 52326036
Name Kidney Transplantation in Highly Sensitized Patients
Downcase Name kidney transplantation in highly sensitized patients

Id Information

Sequence: 40269373 Sequence: 40269374
Id Source org_study_id Id Source secondary_id
Id Value 20-HMedIdes-21 Id Value 2022-500230-28-00
Id Type Other Identifier
Id Type Description EU Trial Number

Countries

Sequence: 42688771
Name Spain
Removed False

Design Groups

Sequence: 55765649
Group Type Experimental
Title Imlifidase
Description Imlifidase is administered intravenously as one infusion of 0.25 mg/kg over 15 minutes within 24 hours prior to transplantation.

Interventions

Sequence: 52637007
Intervention Type Drug
Name Imlifidase
Description 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.

Keywords

Sequence: 80082231 Sequence: 80082222 Sequence: 80082223 Sequence: 80082224 Sequence: 80082225 Sequence: 80082226 Sequence: 80082227 Sequence: 80082228 Sequence: 80082229 Sequence: 80082230 Sequence: 80082232
Name Children Name Desensitization Name Highly sensitized Name Positive crossmatch Name Unlikely to be transplanted Name Kidney transplantation Name Deceased donor Name Living donor Name End-Stage Renal Disease Name Paediatric patients Name Incompatible transplant
Downcase Name children Downcase Name desensitization Downcase Name highly sensitized Downcase Name positive crossmatch Downcase Name unlikely to be transplanted Downcase Name kidney transplantation Downcase Name deceased donor Downcase Name living donor Downcase Name end-stage renal disease Downcase Name paediatric patients Downcase Name incompatible transplant

Design Outcomes

Sequence: 177951111 Sequence: 177951112 Sequence: 177951113 Sequence: 177951114 Sequence: 177951115 Sequence: 177951116 Sequence: 177951117 Sequence: 177951118 Sequence: 177951119 Sequence: 177951120 Sequence: 177951121 Sequence: 177951122 Sequence: 177951123 Sequence: 177951124 Sequence: 177951125 Sequence: 177951126 Sequence: 177951127 Sequence: 177951128 Sequence: 177951129 Sequence: 177951130 Sequence: 177951131 Sequence: 177951132 Sequence: 177951133 Sequence: 177951134
Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type other Outcome Type other
Measure Proportion of patients with conversion of a positive crossmatch test to negative within 24 hours after start of imlifidase treatment Measure Renal function up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR) Measure Renal function up to 5 years after transplantation as assessed by serum/plasma creatinine levels Measure Renal function up to 5 years after transplantation as assessed by serum/plasma cystatin C levels Measure Renal function up to 5 years after transplantation as assessed by proteinuria Measure DSA levels up to 5 years after transplantation Measure Graft survival (death censored) up to 5 year after transplantation Measure Graft failure-free survival up to 5 years after transplantation Measure Patient survival up to 5 years after transplantation Measure Frequency of delayed graft function (DGF) Measure Length of DGF Measure Proportion of patients with dialysis dependency up to 5 years after transplantation Measure Imlifidase Pharmacokinetics (AUC) Measure Imlifidase Pharmacokinetics (Cmax) Measure Imlifidase Pharmacokinetics (tmax) Measure Imlifidase Pharmacokinetics (t1/2) Measure Imlifidase Pharmacokinetics (CL) Measure Imlifidase Pharmacokinetics (Vz) Measure Imlifidase Pharmacodynamic (PD) profile up to 9 days after imlifidase treatment Measure Immunogenicity profile of imlifidase up to 5 years after imlifidase treatment Measure Proportion of patients with biopsy- and serology (DSA)-confirmed AMR up to 5 years after transplantation Measure Proportion of patients with biopsy confirmed cell-mediated rejection (CMR) up to 5 years after transplantation Measure Safety assessed as proportion of patients with infusion related reactions within 48 hours of imlifidase infusion Measure Safety assessed as proportion of patients severe or serious infections within 30 days after imlifidase treatment
Time Frame From start of imlifidase administration to 24 hours Time Frame From pre-dose imlifidase up to 5 years Time Frame From pre-dose imlifidase up to 5 years Time Frame From pre-dose imlifidase up to 5 years Time Frame From pre-dose imlifidase up to 5 years Time Frame From pre-dose imlifidase up to 5 years Time Frame From 6 months up to 5 years Time Frame From 6 months up to 5 years Time Frame From 6 months up to 5 years Time Frame From transplantation up 7 days after transplantation Time Frame From transplantation up 7 days after transplantation Time Frame From 6 months up to 5 years Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 15 Time Frame From pre-dose imlifidase up to Day 10 Time Frame From pre-dose imlifidase up to 5 years Time Frame From transplantation up to 5 years Time Frame From transplantation up to 5 years Time Frame From start of imlifidase infusion up to 48 hours Time Frame From start of imlifidase infusion up to 30 days
Description 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. Description eGFR is a measure of kidney function. Reduced kidney function is characterised by a decreased eGFR value. Description Creatinine is a measure of kidney function. Reduced kidney function is characterised by an increased value. Description Cystatin C is a measure of kidney function. Reduced kidney function is characterised by an increased value. Description Proteinuria (protein/creatinine ratio in urine) is a measure of kidney function. Reduced kidney function is characterised by an increased value. Description Donor specific antibodies (DSAs) are antibodies in the recipient directed against the transplanted organ. Description 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. Description 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. Description AUC = Area under the imlifidase plasma concentration versus time curve. Description Cmax = Maximum observed plasma concentration of imlifidase following dosing. Description tmax = Time point for maximum observed plasma concentration of imlifidase following dosing Description t1/2 = Terminal half-life of imlifidase. Description CL = Clearance of imlifidase. Description Vz = Volume of distribution during the elimination phase Description PD is assessed as serum concentrations of intact IgG and its fractions following infusion. Description Immunogenicity is assessed as serum concentration of anti-imlifidase IgG (ADA). Description Banff scores (Loupy et al. 2020) will be used for biopsy evaluation. Description Banff scores (Loupy et al. 2020) will be used for biopsy evaluation.

Sponsors

Sequence: 48464375
Agency Class INDUSTRY
Lead Or Collaborator lead
Name Hansa Biopharma AB

Overall Officials

Sequence: 29367717
Role Study Director
Name Clinical Operations
Affiliation Hansa Biopharma AB

Central Contacts

Sequence: 12047472
Contact Type primary
Name Central Contact
Phone +46 46 16 56 70
Email clinicalstudyinfo@hansabiopharma.com
Role Contact

Design Group Interventions

Sequence: 68358345
Design Group Id 55765649
Intervention Id 52637007

Eligibilities

Sequence: 30855100
Gender All
Minimum Age 1 Year
Maximum Age 17 Years
Healthy Volunteers No
Criteria Inclusion Criteria: Signed Informed Consent obtained from patient/parent/legal guardian/independent witness (depending on patient's age) before any trial-related procedures Highly sensitised patient with panel reactive antibodies (PRA) ≥80% 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 Patient with end-stage renal disease (ESRD) and waiting for a renal transplant from a living or deceased donor Patient must be transplantable (including size mismatch) at the time of obtaining informed consent for trial participation 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) 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. Willingness and ability to comply with the protocol as judged by the investigator Exclusion Criteria: Previous treatment with imlifidase IVIg treatment within 28 days prior to imlifidase treatment Desensitisation treatment(s) within 1 month prior to the current transplantation Hypersensitivity to the active substance (imlifidase) or to any of the excipients and to other immunosuppressive drugs specified in the protocol Ongoing serious infections Present, or history of, thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP 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 Malignancy within 3 years prior to transplantation ABO blood group incompatible transplantations (A2 and A2B kidneys will not be accepted for B recipients) Any other reason that, in the view of the investigator, precludes transplantation Breast feeding or pregnancy, if applicable 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) Suspicion of Covid-19 infection or positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test Positive serology for human immunodeficiency virus (HIV) Clinical signs of hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), or Epstein Barr virus (EBV) infection Donor with positive serology for HIV, HBV, HCV, CMV or EBV to a patient with negative serology (mismatch serology) Clinically relevant active infection(s) as judged by the investigator Tuberculosis Use of other investigational agents within 5 terminal elimination half-lives prior to the transplantation Contemporaneous participation in medical device studies Known mental incapacity or language barriers precluding patients'/parents'/legal guardians' adequate understanding of the informed consent information and the trial activities Inability by the judgement of the investigator to participate in the trial for any other reason
Adult False
Child True
Older Adult False

Calculated Values

Sequence: 254311605
Number Of Facilities 1
Registered In Calendar Year 2023
Were Results Reported False
Has Us Facility False
Has Single Facility True
Minimum Age Num 1
Maximum Age Num 17
Minimum Age Unit Year
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 21
Number Of Other Outcomes To Measure 2

Designs

Sequence: 30600942
Allocation N/A
Intervention Model Single Group Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking None (Open Label)
Intervention Model Description This is an open-label, non-randomised trial in highly sensitized paediatric kidney transplant patients with positive XM against an available DD or LD. The rationale for a non-randomised trial in DD kidney transplantation is that there are no other effective or approved desensitisation protocols that would provide a suitable or ethical control. The rationale for a non-randomised trial in LD kidney transplantation is that potential control treatments have already been tried unsuccessfully in the patients or such treatments are judged as highly unlikely to succeed based on the breadth and depth of the patients' sensitisation. Treatment with little anticipation of success would expose the patients to unnecessary immunosuppression.

Intervention Other Names

Sequence: 26746575
Intervention Id 52637007
Name IdeS, HMED-IdeS

Responsible Parties

Sequence: 28967451
Responsible Party Type Sponsor

Study References

Sequence: 52230820
Pmid 32463180
Reference Type background
Citation 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.

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