| Outcome Measures: |
Primary: Number of Patients With Crossmatch Conversion (Positive to Negative), IdeS ability to create a negative crossmatch (XM) test in patients who before treatment exhibit Donor Specific Antibodies (DSAs) and have a positive XM test to their available live or deceased donor kidney. XM was assessed using both FACS and CDC XM tests. FACS XM is a multi-staining procedure where the recipient's serum is used to stain donor cells to identify presence of DSAs in recipient's serum. T- and B-cells are identified using conjugated antibodies against CD3 and CD19. DSAs are identified using a conjugated anti-human antibody. CDC XM evaluates the cytotoxic capacity of the DSAs. The recipient's serum is mixed with donor cells prior to addition of complement. Fluorescent dyes are added and the live/dead cells (%) is scored using a fluorescent microscope. CDC XM amplified with anti-human globulin is not compatible with imlifidase and should not be used. The endpoint was met if at least one XM test was positive pre-dose and the last test within 24 h was negative., Within 24 hours of IdeS dosing | Secondary: Number of Patients With Donor Specific Antibodies With an MFI Value >3000, Donor specific antibodies (DSA) level at different time points within 180 days after administration of IdeS. DSA levels were measured using the single antigen beads (SAB) anti-HLA assay. The levels were determined as mean fluorescence intensity (MFI). Positive DSA (i.e. HLA antibodies) were defined as having a MFI value \>3000., Within 180 days after administration of IdeS.|Time to Create a Negative CDC Crossmatch Test, Time to create a negative CDC crossmatch (XM) was defined as the first timepoint all CDC XM results were negative., 2h, 6h, 24h after administration of IdeS.|Time to Create a Negative FACS Crossmatch Test, Time to create a negative FACS crossmatch (XM) was defined as the first timepoint all FACS XM results were negative., 2h, 6h, and 24h after administration of IdeS|Kidney Function After IdeS Treatment Assessed by eGFR, Estimated glomerular filtration rate (eGFR) was calculated as described by the MDRD equation. eGFR is a measure of kidney function. eGFR for a kidney with normal function is 90 mL/min/1.72m2. Kidney disease is characterised by a decreased eGFR value., Within 180 days after administration of IdeS|Serum IgG Concentration After Administration of IdeS, The patient's immunoglobulin G (IgG) is cleaved by IdeS in two steps. The first cut separates one of the heavy chains from the Fc part, generating so called single-cleaved IgG (scIgG), and the second cut separates the other heavy chain from the Fc part, thus generating one F(ab')2 fragment and one Fc fragment. The IgG concentration measured for this outcome is the sum of intact and scIgG because the assay used cannot discriminate between the two. A decrease in IgG concentration therefore represents complete cleavage of the IgG molecules to Fc and F(ab')2 fragments. Please note that intravenous IgG (IVIg) was administered Day 7., Within 180 days after administration of IdeS.|Pharmacokinetics - Cmax (First Dose), Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis), Pre-dose to Day 14 after administration of IdeS.|Pharmacokinetics - Cmax (Second Dose), Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis), Pre-dose until Day 14 after administration of IdeS|Pharmacokinetics - Tmax (First Dose), Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis), Pre-dose to Day 14 after administration of IdeS|Pharmacokinetics - Tmax (Second Dose), Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis), Pre-dose to Day 14 after administration of IdeS|Pharmacokinetics - AUC, AUC = Area under the plasma concentration versus time curve (Non-compartmental PK analysis), Pre-dose to Day 14 after administration of IdeS.|Pharmacokinetics - t1/2, Alpha-t1/2 = Half-life during distribution phase Beta-t1/2 = Half-life during elimination phase Non-compartmental PK analysis, Pre-dose to Day 14 after administration of IdeS.|Pharmacokinetics - CL, CL = Clearance Non compartmental PK analysis, Pre-dose to Day 14|Pharmacokinetics - Vss, Vss = Volume of distribution at steady state Non compartmental PK analysis, Pre-dose to Day 14 after administration of IdeS|Pharmacokinetics - Vz, Vz = Volume of distribution during the elimination phase Non compartmental PK analysis, Pre-dose to Day 14 after administration of IdeS.
|
| Locations: |
Cedars-Sinai Medical Center, Los Angeles, California, 90048, United States|The Johns Hopkins Hospital, Baltimore, Maryland, 21205, United States|New York University School of Medicine, New York, New York, 10016, United States|Necker Hospital, Paris, 75743, France|Uppsala University Hospital, Uppsala, 75185, Sweden
|
