Imlifidase Prior to Kidney Transplant in Highly Sensitised Children

NCT05753930 | Recruiting Phase 2 DMC

• 2 other identifiers: 20-HMedIdes-212022-500230-28-00
• Study Type: interventional
• Target: 10
• Locations: 5 countries
• Sites: 5

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.

Conditions

Kidney Transplantation in Highly Sensitized Patients

Keywords

Desensitization; Highly sensitized; Positive crossmatch; Unlikely to be transplanted; Kidney transplantation; Deceased donor; Living donor; End-Stage Renal Disease; Paediatric patients; Children; Incompatible transplant

Outcome Measures

Primary Outcomes (1)

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

  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.

  From start of imlifidase administration to 24 hours

Secondary Outcomes (21)

• Renal function up to 5 years after transplantation as assessed by estimated glomerular filtration rate (eGFR)

  From pre-dose imlifidase up to 5 years

• Renal function up to 5 years after transplantation as assessed by serum/plasma creatinine levels

  From pre-dose imlifidase up to 5 years

• Renal function up to 5 years after transplantation as assessed by serum/plasma cystatin C levels

  From pre-dose imlifidase up to 5 years

• Renal function up to 5 years after transplantation as assessed by proteinuria

  From pre-dose imlifidase up to 5 years

• DSA levels up to 5 years after transplantation

  From pre-dose imlifidase up to 5 years

Other Outcomes (2)

• Safety assessed as proportion of patients with infusion related reactions within 48 hours of imlifidase infusion

  From start of imlifidase infusion up to 48 hours

• Safety assessed as proportion of patients with severe or serious infections within 30 days after imlifidase treatment

  From start of imlifidase infusion up to 30 days

Study Arms (1)

Imlifidase

EXPERIMENTAL

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

Drug: Imlifidase

Interventions

Imlifidase 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.

Also known as: IdeS, HMED-IdeS

Imlifidase

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (5)

HUS, Helsinki University Hospital

Helsinki, 00290, Finland

WITHDRAWN

Robert Debre University Hospital

Paris, 75019, France

RECRUITING

Hospital Unviersitari Vall d'Hebron, Nefrología Pediátrica

Barcelona, 08035, Spain

RECRUITING

Karolinska University Hospital

Huddinge, Stockholm County, SE-141 86, Sweden

RECRUITING

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 32463180 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Mac-1-like protein, Streptococcus

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Operations

  Hansa Biopharma AB

  STUDY DIRECTOR

Central Study Contacts

Central Contact

CONTACT

+46 46 16 56 70; clinicalstudyinfo@hansabiopharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 3, 2023
• Study Start: June 2, 2023
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): August 31, 2031
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); FI (1); GB (1); ES (1); FR (1)