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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000441-12 | EudraCT Number |
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The purpose of this research study is to evaluate the safety, effect, and pharmacology of C1 Esterase Inhibitor (human) in kidney transplant patients with acute Antibody-Mediated Rejection (AMR).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C1 Esterase Inhibitor (Human) | Experimental | Subjects were to receive C1 esterase inhibitor intravenously at a rate of approximately 1 mL per minute as tolerated. Subjects were to receive a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13 |
|
| Normal Saline | Placebo Comparator | placebo infused as above |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Biological |
| ||
| C1 Esterase Inhibitor (Human) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Histopathology Endpoints | The protocol-specified Day 20 (post-treatment) biopsy was compared to the qualifying biopsy to assess changes in histopathology for light and immunofluorescence microscopy. The Central Pathologist provided the following categorical information from the qualifying biopsy in an AMR Scorecard: C4d Score (0-100), Margination Score (0-100) Glomerulitis Score (0-100), Vasculitis Score (0-100), Glomerulosclerosis Score (0-100), Chronic Glomerulopathy Score (0-100), Interstitial Fibrosis Score (0-100), and the Chronic Vasculitis Score (0-100), with 0 being absence of abnormal histopathology. The "qualifying" renal allograft biopsy was performed as standard of care (SOC) within 12 months after transplant and prior to screening for this study. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. A negative change from baseline indicates that histopathology has improved. Endpoint includes subjects with both Qualifying and Day 20 Biopsies. | Within 72 hours prior to first dose of study drug, Day 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR) | The "qualifying" renal allograft biopsy was performed as standard of care within 12 months after transplant and prior to screening. The qualifying biopsy was used to establish the diagnosis of AMR and was evaluated for all of the following to obtain baseline assessments: the presence of C4d, and monocyte or neutrophil infiltration around the peritubular capillaries (PTCs) and/or glomeruli. The Central Pathologist provided the following information from the qualifying biopsy in an AMR Scorecard: C4d Score, Glomerulitis Score, Vasculitis Score, Glomerulosclerosis Score, Chronic Glomerulopathy Score, Interstitial Fibrosis Score, and the Chronic Vasculitis Score. The Banff AMR Scoring System was used to summarize these scores. Resolution determination was made based on clinical criteria (improvement of serum creatinine ± decrease of DSA titer, and/or increase in urine output) and histopathology. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. |
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Inclusion Criteria include:
Exclusion Criteria include:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ViroPharma Investigative Site | Los Angeles | California | United States | |||
| ViroPharma Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27184779 | Derived | Montgomery RA, Orandi BJ, Racusen L, Jackson AM, Garonzik-Wang JM, Shah T, Woodle ES, Sommerer C, Fitts D, Rockich K, Zhang P, Uknis ME. Plasma-Derived C1 Esterase Inhibitor for Acute Antibody-Mediated Rejection Following Kidney Transplantation: Results of a Randomized Double-Blind Placebo-Controlled Pilot Study. Am J Transplant. 2016 Dec;16(12):3468-3478. doi: 10.1111/ajt.13871. Epub 2016 Jun 27. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received an intravenous (IV) infusion of normal saline, at a rate of approximately 1 mL per minute as tolerated, 7 times over a 2-week period: an initial infusion on Day 1, followed by infusions on Days 3, 5, 7, 9, 11, and 13. |
| FG001 | CINRYZE | Participants received an intravenous (IV) infusion of human C1 esterase inhibitor (CINRYZE) at a rate of approximately 1 mL per minute as tolerated. Participants received a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The Intent-to-Treat (ITT) population, defined as all participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo).
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received an intravenous (IV) infusion of normal saline, at a rate of approximately 1 mL per minute as tolerated, 7 times over a 2-week period: an initial infusion on Day 1, followed by infusions on Days 3, 5, 7, 9, 11, and 13. |
| BG001 | CINRYZE |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR) | The "qualifying" renal allograft biopsy was performed as standard of care within 12 months after transplant and prior to screening. The qualifying biopsy was used to establish the diagnosis of AMR and was evaluated for all of the following to obtain baseline assessments: the presence of C4d, and monocyte or neutrophil infiltration around the peritubular capillaries (PTCs) and/or glomeruli. The Central Pathologist provided the following information from the qualifying biopsy in an AMR Scorecard: C4d Score, Glomerulitis Score, Vasculitis Score, Glomerulosclerosis Score, Chronic Glomerulopathy Score, Interstitial Fibrosis Score, and the Chronic Vasculitis Score. The Banff AMR Scoring System was used to summarize these scores. Resolution determination was made based on clinical criteria (improvement of serum creatinine ± decrease of DSA titer, and/or increase in urine output) and histopathology. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. | The Intent-to-Treat Safety (ITT-S) population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Number | participants | 90 days after start of treatment |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received an intravenous (IV) infusion of normal saline, at a rate of approximately 1 mL per minute as tolerated, 7 times over a 2-week period: an initial infusion on Day 1, followed by infusions on Days 3, 5, 7, 9, 11, and 13. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
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|
|
| 90 days after start of treatment |
| Change From Baseline in Serum Creatinine | Graft function was assessed by measuring serum creatinine. Serum creatinine level was obtained directly from laboratory results. Baseline was the last value collected prior to first dose of study drug. A negative change from baseline indicates that serum creatinine levels have decreased. Values for Day 90 were collected +/= 14 days. | From Day 1 to Days 20 and 90 |
| Change From Baseline in Creatinine Clearance | Graft function was assessed by measuring creatinine clearance. Creatinine clearance was calculated by the Cockcroft-Gault formula. Baseline was the last value collected prior to first dose of study drug. A positive change from baseline indicates that the clearance rate has increased. Values for Day 90 were collected +/= 14 days. | From Day 1 to Days 20 and 90 |
| Number of Plasmapheresis Sessions | If necessary, rescue therapy included plasmapheresis. Participating centers used plasmapheresis for desensitization, if necessary, prior to transplant and also for the treatment of acute AMR. Plasmapheresis therapy was performed for the qualifying episode of AMR according to standards at the investigational site and at the discretion of the investigator. Sessions include those prior to first dose. If plasmapheresis therapy occurred on the same day as study drug dosing, study drug was administered after completion of the plasmapheresis session. | From Day 1 through Days 20 and 90 |
| Number of Participants Who Required Salvage Splenectomy | If necessary, rescue therapy included splenectomy. | From Day 1 to Day 90 |
| Number of Deaths | From Day 1 to Day 90 |
| Number of Participants With Allograft Failure | Allograft failure was determined by the presence of the following criteria: current renal allograft nephrectomy and/or a clinical determination that the allograft irreversibly and irrevocably ceased functioning. | From the day of enrollment to Day 90 |
| Serum Concentrations of C1 Inhibitor (C1 INH) Antigen | Plasma samples were used for the determination of antigenic C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
| Serum Concentrations of C1 INH Functional Activity | Plasma samples were used for the determination of functional C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
| Time to Maximum Plasma Concentration (Tmax) of C1 INH | Plasma samples were used for the determination of antigenic and functional C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
| Area Under The Concentration-Time Curve (AUC) of C1 INH Antigen | Plasma samples were used for the determination of antigenic C1 INH parameters. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), and area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
| Area Under The Concentration-Time Curve (AUC) of C1 INH Functional Activity | Plasma samples were used for the determination of functional C1 INH parameters. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), and area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
| Baltimore |
| Maryland |
| United States |
| ViroPharma Investigative Site | Minneapolis | Minnesota | United States |
| ViroPharma Investigative Site | Cincinnati | Ohio | United States |
| ViroPharma Investigative Site | Heidelberg | Germany |
Participants received an intravenous (IV) infusion of human C1 esterase inhibitor (CINRYZE) at a rate of approximately 1 mL per minute as tolerated. Participants received a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Participants received an intravenous (IV) infusion of normal saline, at a rate of approximately 1 mL per minute as tolerated, 7 times over a 2-week period: an initial infusion on Day 1, followed by infusions on Days 3, 5, 7, 9, 11, and 13. |
| OG001 | CINRYZE | Participants received an intravenous (IV) infusion of human C1 esterase inhibitor (CINRYZE) at a rate of approximately 1 mL per minute as tolerated. Participants received a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13. |
|
|
| Primary | Change From Baseline in Histopathology Endpoints | The protocol-specified Day 20 (post-treatment) biopsy was compared to the qualifying biopsy to assess changes in histopathology for light and immunofluorescence microscopy. The Central Pathologist provided the following categorical information from the qualifying biopsy in an AMR Scorecard: C4d Score (0-100), Margination Score (0-100) Glomerulitis Score (0-100), Vasculitis Score (0-100), Glomerulosclerosis Score (0-100), Chronic Glomerulopathy Score (0-100), Interstitial Fibrosis Score (0-100), and the Chronic Vasculitis Score (0-100), with 0 being absence of abnormal histopathology. The "qualifying" renal allograft biopsy was performed as standard of care (SOC) within 12 months after transplant and prior to screening for this study. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. A negative change from baseline indicates that histopathology has improved. Endpoint includes subjects with both Qualifying and Day 20 Biopsies. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | scores on a scale | Within 72 hours prior to first dose of study drug, Day 20 |
|
|
|
|
| Secondary | Change From Baseline in Serum Creatinine | Graft function was assessed by measuring serum creatinine. Serum creatinine level was obtained directly from laboratory results. Baseline was the last value collected prior to first dose of study drug. A negative change from baseline indicates that serum creatinine levels have decreased. Values for Day 90 were collected +/= 14 days. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | mg/dL | From Day 1 to Days 20 and 90 |
|
|
|
|
| Secondary | Change From Baseline in Creatinine Clearance | Graft function was assessed by measuring creatinine clearance. Creatinine clearance was calculated by the Cockcroft-Gault formula. Baseline was the last value collected prior to first dose of study drug. A positive change from baseline indicates that the clearance rate has increased. Values for Day 90 were collected +/= 14 days. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | mL/min | From Day 1 to Days 20 and 90 |
|
|
|
|
| Secondary | Number of Plasmapheresis Sessions | If necessary, rescue therapy included plasmapheresis. Participating centers used plasmapheresis for desensitization, if necessary, prior to transplant and also for the treatment of acute AMR. Plasmapheresis therapy was performed for the qualifying episode of AMR according to standards at the investigational site and at the discretion of the investigator. Sessions include those prior to first dose. If plasmapheresis therapy occurred on the same day as study drug dosing, study drug was administered after completion of the plasmapheresis session. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | sessions | From Day 1 through Days 20 and 90 |
|
|
|
|
| Secondary | Number of Participants Who Required Salvage Splenectomy | If necessary, rescue therapy included splenectomy. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Number | participants | From Day 1 to Day 90 |
|
|
|
| Secondary | Number of Deaths | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Number | participants | From Day 1 to Day 90 |
|
|
|
| Secondary | Number of Participants With Allograft Failure | Allograft failure was determined by the presence of the following criteria: current renal allograft nephrectomy and/or a clinical determination that the allograft irreversibly and irrevocably ceased functioning. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Number | participants | From the day of enrollment to Day 90 |
|
|
|
| Secondary | Serum Concentrations of C1 Inhibitor (C1 INH) Antigen | Plasma samples were used for the determination of antigenic C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | Posted | Mean | Standard Deviation | g/L | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
|
|
|
| Secondary | Serum Concentrations of C1 INH Functional Activity | Plasma samples were used for the determination of functional C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | Units/mL | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
|
|
|
| Secondary | Time to Maximum Plasma Concentration (Tmax) of C1 INH | Plasma samples were used for the determination of antigenic and functional C1 INH concentrations. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Median | Full Range | hours | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
|
|
|
| Secondary | Area Under The Concentration-Time Curve (AUC) of C1 INH Antigen | Plasma samples were used for the determination of antigenic C1 INH parameters. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), and area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | g*h/L | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
|
|
|
| Secondary | Area Under The Concentration-Time Curve (AUC) of C1 INH Functional Activity | Plasma samples were used for the determination of functional C1 INH parameters. Primary pharmacokinetic (PK) parameters were calculated using baseline-corrected concentration-versus-time data following the last dose and noncompartmental techniques, as appropriate. The following PK parameters were calculated: baseline concentration (Cbaseline), maximum concentration (Cmax), average concentration at steady-state (Cav,ss), time to maximum concentration (tmax), minimum concentration (Cmin), and area under the concentration-time curve from time zero to last quantifiable concentration at time t (AUC0-t). Blood was collected on Day 13 at the indicated timepoints. If plasmapheresis was performed on a dosing day, blood samples were obtained before plasmapheresis, prior to study drug administration (post-plasmapheresis), and at time points relative to the start of infusion. | The ITT-S population, defined as participants who received at least 1 dose (or any portion of a dose) of study drug (CINRYZE or placebo). | Posted | Mean | Standard Deviation | Units*h/mL | Day 13 pre-plasmapheresis (if performed) and pre-dose then 0.5, 2, 24, 48, 96, 168 and 288 (optional) hours post start of infusion |
|
|
|
| 3 |
| 9 |
| 6 |
| 9 |
| EG001 | CINRYZE | Participants received an intravenous (IV) infusion of human C1 esterase inhibitor (CINRYZE) at a rate of approximately 1 mL per minute as tolerated. Participants received a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13. | 1 | 9 | 9 | 9 |
| Transplant rejection | Immune system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Erosive oesophagitis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| Inflammatory pain | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Medical device complication | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Transplant rejection | Immune system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
|
| Incisional hernia | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Perinephric collection | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Wound secretion | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA 16.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Obesity | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| D015843 |
| Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003169 | Complement Inactivator Proteins |
| D003165 | Complement System Proteins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| Glomerulitis score |
|
| Vasculitis score |
|
| Glomerulosclerosis score |
|
| Chronic glomerulopathy score |
|
| Interstitial fibrosis score |
|
| Chronic vasculitis score |
|
Analysis of margination score |
| ANOVA |
| 0.0768 |
The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. |
| Mean treatment difference |
| 18.56 |
| 2-Sided |
| 95 |
| 1.43 |
| 35.68 |
| Superiority or Other (legacy) |
| Analysis of glomerulitis score | ANOVA | 0.6928 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | -4.00 | 2-Sided | 95 | -21.36 | 13.36 | Superiority or Other (legacy) |
| Analysis of vasculitis score | ANOVA | 0.0508 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | 7.11 | 2-Sided | 95 | 1.23 | 12.99 | Superiority or Other (legacy) |
| Analysis of glomerulosclerosis score | ANOVA | 0.2042 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | -4.89 | 2-Sided | 95 | -11.34 | 1.56 | Superiority or Other (legacy) |
| Analysis of chronic glomerulopathy score | ANOVA | 0.3322 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | -0.22 | 2-Sided | 95 | -0.61 | 0.17 | Superiority or Other (legacy) |
| Analysis of interstitial fibrosis score | ANOVA | 0.4723 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | 5.67 | 2-Sided | 95 | -7.77 | 9.11 | Superiority or Other (legacy) |
| Analysis of chronic vasculitis score | ANOVA | 0.5103 | The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. | Mean treatment difference | 4.56 | 2-Sided | 95 | -7.25 | 16.37 | Superiority or Other (legacy) |
Analysis of Day 90 |
| ANOVA |
| 0.9533 |
The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. |
| Mean treatment difference |
| -0.01 |
| 2-Sided |
| 95 |
| -0.44 |
| 0.41 |
| Superiority or Other (legacy) |
Analysis of Day 90 |
| ANOVA |
| 0.5895 |
The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. |
| Mean treatment difference |
| 4.68 |
| 2-Sided |
| 95 |
| -10.19 |
| 19.55 |
| Superiority or Other (legacy) |
Analysis of Day 1 through Day 90 |
| ANOVA |
| 0.9470 |
The p-value for testing the mean for the treatment difference comparison assessed from ANOVA model analysis for CINRYZE versus placebo. |
| Mean treatment difference |
| 0.24 |
| 2-Sided |
| 90 |
| -6.05 |
| 6.52 |
| Superiority or Other (legacy) |
| Cmax, n=9, 9 |
|
| Cavg, n=5, 9 |
|
| Cmax, n=9, 9 |
|
| Cavg, n=6, 8 |
|