An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients

Hansa Biopharma

Status and phase: Completed; Phase 2

Conditions: Kidney Transplant Rejection

Treatments: Drug: Imlifidase; Other: Plasma Exchange

Study type: Interventional

Funder types: Industry

Identifiers

NCT03897205

2018-000022-66 (EudraCT Number)

16-HMedIdeS-12

Details and patient eligibility

About

The purpose of this study was to investigate how efficiently the study medication imlifidase reduces the amount of donor specific antibodies (DSA) in comparison with plasma exchange (PE) therapy, in patients who have had an active or chronic active antibody mediated rejection (AMR) after being kidney transplanted. The purpose was also to investigate and compare safety for these two treatments.

Full description

Antibodies to HLA antigens have a strong correlation with allograft injury and loss. Treatment with imlifidase, PE and immunoabsorption (IA) all aim to reduce antibody levels.

This study will compare the reduction in DSA levels after treatment with imlifidase and PE in patients diagnosed with active or chronic active AMR (according to Banff 2017 criteria) having at least a 25% rise in serum creatinine compared with last measurement prior to the AMR (Patients with delayed graft function and AMR within 10 days after kidney transplantation can be included regardless of serum creatinine level).

Included patients will be randomized to receive either 1 dose of imlifidase (0.25 mg/kg) or 5-10 sessions of PEs (IA may replace PE at the discretion of the investigator). All patients will receive pulse methylprednisolone for 3 days, starting before the 1st treatment, followed by a tapering schedule with prednisolone/prednisone. The patients will also receive high dose IVIg 3 days after imlifidase treatment or directly after the last PE. In addition a single dose of rituximab will be given 5 days after completed IVIg infusion.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed Informed Consent obtained before any study-related procedures
2. Willingness and ability to comply with the protocol
3. Male and/or female donor kidney recipients age ≥18 years at the time of screening
4. Presence of DSA(s)
5. Meet the Banff 2017 criteria for active or chronic active AMR
6. At least 25% rise in serum creatinine compared to last individual value taken prior to the AMR. Patients with delayed graft function and AMR within 10 days after transplant (confirmed by kidney biopsy) can be included regardless of serum creatinine level
7. Women of child-bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, 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
8. Men willing to use double-barrier contraception from the first day of treatment until at least 2 months after the dose of imlifidase, if not abstinent

Exclusion criteria

1. Previous treatment with imlifidase
2. Previous high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion
3. Lactating or pregnant females
4. Significantly abnormal general serum screening lab results judged inappropriate for inclusion in the study by the investigator
5. Intake of other investigational drugs within 5 half-lives (or similar) of the product prior to inclusion
6. Clinically relevant active infection(s) as judged by the investigator
7. Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study such as severe immune deficiency and severe cardiac insufficiency [New York Heart Association (NYHA) Class IV] or severe uncontrolled heart disease
8. Known allergy/sensitivity to imlifidase, IVIg and/or rituximab and the respective excipients
9. Patient unable to tolerate treatment with plasmapheresis or immunoadsorption, as judged by the investigator
10. Unsuitable to participate in the study for any other reason as judged by the investigator
11. Positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection
12. Current diagnosis or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Imlifidase

Experimental group

Description:

Subjects randomized to imlifidase treatment will receive one intravenous dose of imlifidase, 0.25 mg/kg, administered over 15 minutes.

Treatment:

Drug: Imlifidase

Plasma Exchange

Active Comparator group

Description:

Subjects randomized to plasma exchange (PE) treatment will receive 5-10 sessions of PE, as judged by the investigator. Immunoadsorption (IA) may replace PE, at the discretion of the investigator.

Treatment:

Other: Plasma Exchange