Kidney Failure, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the effectiveness of the study drug IdeS in patients who are on the waiting list for kidney transplant and have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. At study entry, the patients will have an available deceased or live donor with a positive crossmatch test. The study will assess IdeS efficacy and safety in removing Donor Specific Antibodies (DSAs) and thereby convert a positive crossmatch test to negative.
Detailed description
The study will assess the IdeS efficacy in creating a negative crossmatch test (XM) in patients who exhibit donor specific antibodies (DSA) and have a positive crossmatch test to their available live or deceased donors. The first 3 patients in this study will receive a kidney from a deceased donor. The study will primarily examine the efficacy of IdeS in creating a negative XM. The first 3 patients will receive one dose of 0.25 mg/kg BW IdeS on study day 0. If it is considered safe and negative crossmatch test is not achieved after the first dose, an additional IdeS infusion can be given within 2 days of the first infusion. The dose schedule may be increased to 0.5 mg/kg BW given once or twice after the first 3 patients have been tested. The decision to escalate the dose will be done after evaluation of safety and efficacy.
Interventions
DRUGIdeS
One dose of 0.25 mg/kg BW IdeS on study day 0. If negative crossmatch is not achieved, a second dose can be given within 2 days of the first infusion.
PROCEDUREKidney transplantation
Performed following IdeS treatment
Sponsors
Hansa Biopharma AB
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients on the kidney transplant waitlist who have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. The breadth and strength of sensitization will predict an extremely low likelihood of successful desensitization or kidney paired donation. * Patients with a live or deceased donor with a positive crossmatch test.
Exclusion criteria
* Previous treatment with IdeS * Previous high dose IVIg treatment (2 g/kg BW) within 28 days prior to IdeS treatment * Lactating or pregnant females * Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception * HIV-positive patients * Patients with clinical signs of HBV or HCV infection * Patients with active tuberculosis * A significantly abnormal general serum screening lab result according to the investigator's judgement. Hgb cannot be \< 6.0 g/dL * Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure \> NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD * Individuals deemed unable to comply with the protocol * Patients with clinical signs of CMV or EBV infection * Patients with a history of major thrombotic events, patients with active peripheral vascular disease or patients with proven hypercoagulable conditions * Patients should not have received investigational drugs within 4 half-lives (or similar) * Known allergy/sensitivity to IdeS infusions * Patients who have a live donor and test positive for ImmunoCap anti-IdeS IgE
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Crossmatch Conversion (Positive to Negative) | Within 24 hours of IdeS dosing | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Create a Negative CDC Crossmatch Test | 2h, 6h, 24h after administration of IdeS. | Time to create a negative CDC crossmatch (XM) was defined as the first timepoint all CDC XM results were negative. |
| Time to Create a Negative FACS Crossmatch Test | 2h, 6h, and 24h after administration of IdeS | Time to create a negative FACS crossmatch (XM) was defined as the first timepoint all FACS XM results were negative. |
| Kidney Function After IdeS Treatment Assessed by eGFR | Within 180 days after administration of IdeS | 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. |
| Serum IgG Concentration After Administration of IdeS | Within 180 days 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. |
| Pharmacokinetics - Cmax (First Dose) | Pre-dose to Day 14 after administration of IdeS. | Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis) |
| Pharmacokinetics - Cmax (Second Dose) | Pre-dose until Day 14 after administration of IdeS | Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis) |
| Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Within 180 days after administration of IdeS. | 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. |
| Pharmacokinetics - Tmax (Second Dose) | Pre-dose to Day 14 after administration of IdeS | Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis) |
| Pharmacokinetics - AUC | Pre-dose to Day 14 after administration of IdeS. | AUC = Area under the plasma concentration versus time curve (Non-compartmental PK analysis) |
| Pharmacokinetics - t1/2 | Pre-dose to Day 14 after administration of IdeS. | Alpha-t1/2 = Half-life during distribution phase Beta-t1/2 = Half-life during elimination phase Non-compartmental PK analysis |
| Pharmacokinetics - CL | Pre-dose to Day 14 | CL = Clearance Non compartmental PK analysis |
| Pharmacokinetics - Vss | Pre-dose to Day 14 after administration of IdeS | Vss = Volume of distribution at steady state Non compartmental PK analysis |
| Pharmacokinetics - Vz | Pre-dose to Day 14 after administration of IdeS. | Vz = Volume of distribution during the elimination phase Non compartmental PK analysis |
| Pharmacokinetics - Tmax (First Dose) | Pre-dose to Day 14 after administration of IdeS | Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis) |
Countries
France, Sweden, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| One Dose of IdeS (0.25 mg/kg BW) IdeS: One dose of 0.25 mg/kg BW IdeS on study day 0.
Kidney transplantation: Performed following IdeS treatment | 16 |
| Two Doses of IdeS (2 x 0.25 mg/kg BW) Two (2) IdeS intravenous infusions
IdeS: First dose of 0.25 mg/kg BW IdeS on study day 0. Second dose of 0.25 mg/kg BW within 2 days of the first infusion.
Kidney transplantation: Performed following IdeS treatment | 3 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Patient graft failure - nephrectomy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | One Dose of IdeS (0.25 mg/kg BW) | Two Doses of IdeS (2 x 0.25 mg/kg BW) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 3 Participants | 19 Participants |
| Age, Continuous | 40 years | 45 years | 40 years |
| Race/Ethnicity, Customized Asian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black or african american | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Indian | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 11 participants | 1 participants | 12 participants |
| Region of Enrollment France | 3 participants | 0 participants | 3 participants |
| Region of Enrollment Sweden | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 12 participants | 2 participants | 14 participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 2 Participants | 13 Participants |
| Weight | 74.05 kg | 68.0 kg | 71.6 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 3 | 0 / 19 |
| other Total, other adverse events | 15 / 16 | 3 / 3 | 18 / 19 |
| serious Total, serious adverse events | 12 / 16 | 3 / 3 | 15 / 19 |
Outcome results
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.
Time frame: Within 24 hours of IdeS dosing
Population: The full analysis set (FAS) comprises data from all patients in the safety analysis set (SAS) with available post-dose efficacy data. Before analysis it was specified that the analysis set should include all patients combined who had received the planned dose which was defined as 1 administration initially which could be repeated if needed. The single as well as the repeated administration are defined as the only planned dose. Consequently, the results are presented for all patients together.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Crossmatch Conversion (Positive to Negative) | XM conversion within 24 h | 17 Patients |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Crossmatch Conversion (Positive to Negative) | No XM conversion within 24 h | 2 Patients |
Secondary
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.
Time frame: Within 180 days after administration of IdeS
Population: The per protocol (PP) set comprises all patients in the SAS with \>1 post dose result. Data excluded for patients with \>1 protocol deviation. 1 patient lost the graft D77. Before analysis it was specified that the PP set should include all patients combined who had received the planned dose defined as 1 admin. initially which could be repeated if needed. The single as well as the repeated admin. are defined as the only planned dose. Hence, the results are presented for all patients together.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 28 | eGFR: >60 ml/min/1.72m2 | 4 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 28 | eGFR: <30 ml/min/1.72m2 | 5 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 28 | eGFR: 30-59 ml/min/1.72m2 | 9 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 90 | eGFR: <30 ml/min/1.72m2 | 4 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 90 | eGFR: 30-59 ml/min/1.72m2 | 7 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 90 | eGFR: >60 ml/min/1.72m2 | 6 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 180 | eGFR: <30 ml/min/1.72m2 | 2 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 180 | eGFR: 30-59 ml/min/1.72m2 | 11 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Kidney Function After IdeS Treatment Assessed by eGFR | Day 180 | eGFR: >60 ml/min/1.72m2 | 4 Participants |
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.
Time frame: Within 180 days after administration of IdeS.
Population: The per protocol (PP) set comprises all patients in the SAS with \>1 post dose result. Data excluded for patients with \>1 protocol deviation. 1 patient lost the graft D77. Before analysis it was specified that the PP set should include all patients combined who had received the planned dose defined as 1 admin. initially which could be repeated if needed. The single as well as the repeated admin. are defined as the only planned dose. Hence, the results are presented for all patients together.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Pre-dose | 17 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Day 180 | 7 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | 2 h | 7 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | 6 h | 3 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | 24 h | 3 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | 48 h | 3 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | 96 h | 6 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Day 7 | 9 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Day 14 | 13 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Day 28 | 10 Patients with DSA (MFI>3000) |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Number of Patients With Donor Specific Antibodies With an MFI Value >3000 | Day 90 | 8 Patients with DSA (MFI>3000) |
Secondary
Pharmacokinetics - AUC
AUC = Area under the plasma concentration versus time curve (Non-compartmental PK analysis)
Time frame: Pre-dose to Day 14 after administration of IdeS.
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~Data available for 9 patients only who all received 1 dose of IdeS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - AUC | 156.09 hour*microgram/mL | Geometric Coefficient of Variation 45.4 |
Secondary
Pharmacokinetics - CL
CL = Clearance Non compartmental PK analysis
Time frame: Pre-dose to Day 14
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~Data available for 9 patients only who all received 1 dose of IdeS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - CL | 1.60 mL/h/kg | Geometric Coefficient of Variation 45.4 |
Secondary
Pharmacokinetics - Cmax (First Dose)
Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)
Time frame: Pre-dose to Day 14 after administration of IdeS.
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value.~The concentration vs time profiles for all 18 patients, including the 3 patients who received a second dose, were used to calculate Cmax after first dose. Cmax after the first dose occurred before the second dose was administered.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Cmax (First Dose) | 3.95 microgram/mL | Geometric Coefficient of Variation 25.2 |
Secondary
Pharmacokinetics - Cmax (Second Dose)
Cmax = Maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)
Time frame: Pre-dose until Day 14 after administration of IdeS
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~The 3 patients received their second dose 11-13 hours after the first dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Cmax (Second Dose) | 4.13 micrograms/mL | Geometric Coefficient of Variation 29.4 |
Secondary
Pharmacokinetics - t1/2
Alpha-t1/2 = Half-life during distribution phase Beta-t1/2 = Half-life during elimination phase Non-compartmental PK analysis
Time frame: Pre-dose to Day 14 after administration of IdeS.
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~Data available for 9 patients only who all received 1 dose of IdeS. (The mean result refers to the harmonic mean.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - t1/2 | t1/2 (alpha) | 4.58 hours | Standard Deviation 3.85 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - t1/2 | t1/2 (beta) | 76.30 hours | Standard Deviation 42.76 |
Secondary
Pharmacokinetics - Tmax (First Dose)
Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)
Time frame: Pre-dose to Day 14 after administration of IdeS
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value.~(The mean result presented refers to the arithmetic mean) The concentration vs time profiles for all 18 patients, including the 3 patients who received a second dose, were used to calculate Tmax for the first dose. Cmax/Tmax for the first dose occurred before the second dose was administered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Tmax (First Dose) | 2.21 hours | Standard Deviation 0.31 |
Secondary
Pharmacokinetics - Tmax (Second Dose)
Tmax = Time point for maximum observed plasma concentration of IdeS following dosing (Non-compartmental PK analysis)
Time frame: Pre-dose to Day 14 after administration of IdeS
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~The 3 subjects received their second dose 11-13 hours after the first dose. Tmax for the second dose was calculated from the start of the first dose.~(The mean result presented refers to the arithmetic mean.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Tmax (Second Dose) | 15.98 hours | Standard Deviation 5.5 |
Secondary
Pharmacokinetics - Vss
Vss = Volume of distribution at steady state Non compartmental PK analysis
Time frame: Pre-dose to Day 14 after administration of IdeS
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~Data available for 9 patients only who all received 1 dose of IdeS.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Vss | 0.14 L/kg | Geometric Coefficient of Variation 26.9 |
Secondary
Pharmacokinetics - Vz
Vz = Volume of distribution during the elimination phase Non compartmental PK analysis
Time frame: Pre-dose to Day 14 after administration of IdeS.
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~Data available for 9 patients only who all received 1 dose of IdeS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Pharmacokinetics - Vz | 0.19 L/kg | Geometric Coefficient of Variation 27 |
Secondary
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.
Time frame: Within 180 days after administration of IdeS.
Population: The Per Protocol (PP) analysis set consists of all patients in the safety set who had at least one efficacy endpoint value. Data from patients with one or more major protocol deviations were excluded.~At Day 180 data was available for 7 patients receiving one dose and 1 patient receiving two doses.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 14) | 13.48 mg/mL | Geometric Coefficient of Variation 55.67 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 21) | 10.57 mg/mL | Geometric Coefficient of Variation 58.67 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (pre-dose) | 10.11 mg/mL | Geometric Coefficient of Variation 85.92 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 28) | 10.25 mg/mL | Geometric Coefficient of Variation 69.85 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (24 h) | 0.37 mg/mL | Geometric Coefficient of Variation 79.14 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 64) | 11.91 mg/mL | Geometric Coefficient of Variation 71.52 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 180) | 9.33 mg/mL | Geometric Coefficient of Variation 42.58 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (48 h) | 0.51 mg/mL | Geometric Coefficient of Variation 129.17 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 before IVIg) | 0.64 mg/mL | Geometric Coefficient of Variation 107.44 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 after IVIg) | 16.52 mg/mL | Geometric Coefficient of Variation 49.9 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (2 h) | 1.19 mg/mL | Geometric Coefficient of Variation 91.05 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 9) | 15.34 mg/mL | Geometric Coefficient of Variation 85.32 |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (6 h) | 0.55 mg/mL | Geometric Coefficient of Variation 83.44 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (24 h) | 0.15 mg/mL | Geometric Coefficient of Variation 42.46 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 14) | 10.85 mg/mL | Geometric Coefficient of Variation 53.42 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (6 h) | 0.38 mg/mL | Geometric Coefficient of Variation 109.18 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 9) | 26.94 mg/mL | Geometric Coefficient of Variation 50.82 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 21) | 5.88 mg/mL | Geometric Coefficient of Variation 88.3 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (48 h) | 0.17 mg/mL | Geometric Coefficient of Variation 45.57 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 64) | 7.77 mg/mL | Geometric Coefficient of Variation 45.82 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 28) | 11.53 mg/mL | Geometric Coefficient of Variation 66.45 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 after IVIg) | 18.47 mg/mL | Geometric Coefficient of Variation 23.91 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 before IVIg) | 0.2 mg/mL | Geometric Coefficient of Variation 96.88 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (2 h) | 0.68 mg/mL | Geometric Coefficient of Variation 165.87 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 180) | 8.99 mg/mL | Geometric Coefficient of Variation 0 |
| PP - Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (pre-dose) | 8.35 mg/mL | Geometric Coefficient of Variation 55.37 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 180) | 9.28 mg/mL | Geometric Coefficient of Variation 39.21 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (24 h) | 0.32 mg/mL | Geometric Coefficient of Variation 83.92 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 64) | 11.09 mg/mL | Geometric Coefficient of Variation 69.02 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (pre-dose) | 9.79 mg/mL | Geometric Coefficient of Variation 79.73 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (2 h) | 1.08 mg/mL | Geometric Coefficient of Variation 100.51 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (6 h) | 0.52 mg/mL | Geometric Coefficient of Variation 85.49 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (48 h) | 0.43 mg/mL | Geometric Coefficient of Variation 132.55 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 before IVIg) | 0.53 mg/mL | Geometric Coefficient of Variation 122.3 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 7 after IVIg) | 16.89 mg/mL | Geometric Coefficient of Variation 45.05 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 9) | 16.85 mg/mL | Geometric Coefficient of Variation 83 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 14) | 13 mg/mL | Geometric Coefficient of Variation 54.34 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 21) | 9.58 mg/mL | Geometric Coefficient of Variation 66.04 |
| PP - One or Two Doses of 0.25 mg/kg BW IdeS | Serum IgG Concentration After Administration of IdeS | IgG concentration (Day 28) | 10.45 mg/mL | Geometric Coefficient of Variation 67.16 |
Secondary
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.
Time frame: 2h, 6h, 24h after administration of IdeS.
Population: The full analysis set (FAS) comprises data from all patients in the safety analysis set (SAS) with available post-dose efficacy data. Before analysis it was specified that the analysis set should include all patients combined who had received the planned dose which was defined as 1 administration initially which could be repeated if needed. The single as well as the repeated administration are defined as the only planned dose. Consequently, the results are presented for all patients together.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative CDC Crossmatch Test | All CDC XM tests negative at 2h | 6 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative CDC Crossmatch Test | All CDC XM tests negative already pre-dose | 3 Participants |
Secondary
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.
Time frame: 2h, 6h, and 24h after administration of IdeS
Population: The full analysis set (FAS) comprises data from all patients in the safety analysis set (SAS) with available post-dose efficacy data. Before analysis it was specified that the analysis set should include all patients combined who had received the planned dose which was defined as 1 administration initially which could be repeated if needed. The single as well as the repeated administration are defined as the only planned dose. Consequently, the results are presented for all patients together.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative FACS Crossmatch Test | All FACS XM tests negative at 2h | 8 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative FACS Crossmatch Test | All FACS XM tests negative at 6h | 2 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative FACS Crossmatch Test | All FACS XM tests negative at 24h | 7 Participants |
| FAS - One or Two Doses of 0.25 mg/kg BW IdeS | Time to Create a Negative FACS Crossmatch Test | Remained positive | 2 Participants |