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

Maximum reduction (%) in the sum of DSA at any time point during the 5 days following the start of treatment. Only DSA with ≥1000 mean fluorescence intensity (MFI) at pre-treatment were included in the calculations. Clarification: The higher the maximum reduction percentage the lower the remaining DSA level.

Time frame: Start of treatment until 5 days following start of treatment

Population: Participants with MFI values less than 1000 were excluded from the analysis

Samples were collected and analysed for presence of anti-imlifidase IgG throughout the study. Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes. Patients who have been exposed to Streptococcus prior to participating in this trial tested positive for ADA also before exposure to imlifidase.

Time frame: Screening until Day 180

An MFI value above 6000 is indicative of complement fixation. Analysis of DSA functionality assessed as mean MFI levels was done before and after treatment.

Time frame: Screening until Day 6

Population: Data was missing for a number of patients.

eGFR as calculated from p-creatinine is a measure of kidney function. eGFR was assessed at all visits throughout the study.

Time frame: Screening until Day 180

Population: Some patients had missing values at sporadic occasions.

Total number of administered PE and IA sessions to each treatment group are presented during the complete trial (Day 1 to Day 180) and for the time period: start of IVIg administration to Day 180.

Time frame: Day 1 to Day 180

Population: In total 4 patients from the imlifidase arm were treated with PE. Of these 3 patients received PE after start of IVIg.~All 10 patients from the PE arm were treated with PE. Of these 1 patient received PE after start of IVIg.~One (1) patient from the PE arm also received IA after start of IVIg.

Kidney biopsies were assessed according to the Banff (2017) criteria at screening (baseline), Day 29, and Day 180. Abbreviations: AMR=Antibody mediated rejection, CMR=cell-mediated rejection

Time frame: Screening, Day 29 and Day 180

Information on patients who experienced graft loss was collected throughout the study.

Time frame: Screening until Day 180

Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot. Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.

Time frame: Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)

Population: IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence measurement of intact IgG was not performed for this group from 96 hours onwards. Measurement was stopped for PE patients when IVIg was administered.

Kidney biopsies were taken at screening, Day 29, and Day 180. Changes from baseline in mRNA levels were assessed as evidence of resolved AMR.

Time frame: Screening, Day 29, and Day 180

Biopsies collected 180 days after treatment were analysed for signs of glomerulopathy.

Time frame: Day 180

Cmax = Maximum observed plasma concentration of imlifidase following dosing

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Area under the imlifidase plasma concentration vs time curve (AUC)

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Clearance (CL) of imlifidase means the volume of blood cleared of imlifidase per unit of time.

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

t1/2 = terminal half-life of imlifidase (refers to the time required for plasma concentration of a drug to decrease by 50%) Different mathematical models are available to describe how drugs are adsorbed, distributed, metabolised, and eliminated from the body. The time-concentration curve of imlifidase could be fitted to the so called 2-compartment model. This model divide the body into a central and an peripheral compartment. The central compartment consist of the plasma and tissues where the distribution is fast and the peripheral consists of tissues where the distribution of the drug is slower. As a result the elimination of imlifidase consists of an initial phase with a short half life (alpha-t1/2) and an elimination phase with a longer half-life (beta-t1/2).

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Population: The data presents only patients who's time-concentration profile could be fitted to a 2-compartment model

Tmax = Time point for maximum observed plasma concentration of imlifidase following dosing

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Vss = volume of distribution associated with steady state VZ = volume of distribution associated with the elimination phase

Time frame: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

DSA levels were assessed at all visits throughout the study. The results are presented as reduction (%) from baseline. Clarification: The higher the reduction percentage the lower the remaining DSA level. Please observe that a negative reduction value represents an increase in DSA level from baseline.

Time frame: Screening until Day 180

Total serum IgG levels over time following treatment until administration of IVIg. Please observe, IVIg was initiated on Day 4 (before 96 h measurement) for the imlifidase group.

Time frame: Pre-dose until Day 6

The albumine/creatinine ratio in urine is a measure of kidney function.

Time frame: Pre-dose until Day 180

Population: Some patients had missing data at different occasions during the study.