- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01147302
A Pilot Study to Evaluate the Use of C1 Esterase Inhibitor (Human) in Patients With Acute Antibody-Mediated Rejection
June 2, 2021 updated by: Shire
A Randomized Double-Blind Placebo-Controlled Pilot Study to Evaluate the Safety and Effect of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Treatment of Acute Antibody-Mediated Rejection in Recipients of Donor-Sensitized Kidney Transplants
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).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
18
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Heidelberg, Germany
- ViroPharma Investigative Site
-
-
-
-
California
-
Los Angeles, California, United States
- ViroPharma Investigative Site
-
-
Maryland
-
Baltimore, Maryland, United States
- ViroPharma Investigative Site
-
-
Minnesota
-
Minneapolis, Minnesota, United States
- ViroPharma Investigative Site
-
-
Ohio
-
Cincinnati, Ohio, United States
- ViroPharma Investigative Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria include:
- ≥18 years of age.
- Weigh ≥50 kg.
- Donor specific antibody identified.
Exclusion Criteria include:
- Any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
- History of allergic reaction to C1 Esterase Inhibitor or other blood products.
- Participation in the active dosing phase of any other investigational drug study within 30 days prior to dosing with study drug.
- Pregnancy or lactation.
- Receipt of any experimental agents for AMR within 1 month prior to the first dose of study drug.
- Any infection that causes hemodynamic compromise.
- History of bleeding or clotting abnormality.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: C1 Esterase Inhibitor (Human)
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
|
Other Names:
|
PLACEBO_COMPARATOR: Normal Saline
placebo infused as above
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Histopathology Endpoints
Time Frame: Within 72 hours prior to first dose of study drug, Day 20
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Resolution of The Qualifying Episode of Antibody-Mediated Rejection (AMR)
Time Frame: 90 days after start of treatment
|
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.
|
90 days after start of treatment
|
Change From Baseline in Serum Creatinine
Time Frame: From Day 1 to Days 20 and 90
|
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
Time Frame: From Day 1 to Days 20 and 90
|
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
Time Frame: From Day 1 through Days 20 and 90
|
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
Time Frame: From Day 1 to Day 90
|
If necessary, rescue therapy included splenectomy.
|
From Day 1 to Day 90
|
Number of Deaths
Time Frame: From Day 1 to Day 90
|
From Day 1 to Day 90
|
|
Number of Participants With Allograft Failure
Time Frame: From the day of enrollment to Day 90
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
Time Frame: 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
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
August 24, 2011
Primary Completion (ACTUAL)
April 19, 2013
Study Completion (ACTUAL)
June 28, 2013
Study Registration Dates
First Submitted
June 16, 2010
First Submitted That Met QC Criteria
June 16, 2010
First Posted (ESTIMATE)
June 22, 2010
Study Record Updates
Last Update Posted (ACTUAL)
June 11, 2021
Last Update Submitted That Met QC Criteria
June 2, 2021
Last Verified
June 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0624-201
- 2012-000441-12 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Graft Rejection
-
Exosome Diagnostics, Inc.Not yet recruitingGraft Rejection
-
University of Erlangen-Nürnberg Medical SchoolCompleted
-
Aravind Eye Care SystemUnknownCorneal Graft RejectionIndia
-
Shahid Beheshti University of Medical SciencesCompletedEndothelial Graft RejectionIran, Islamic Republic of
-
Paul KimAstellas Pharma IncCompletedAcute Graft Rejection | Heart Transplant | Chronic Graft RejectionUnited States
-
Leiden University Medical CenterCompletedRejection | Graft LossNetherlands
-
Mahmoud adel shaabanUnknownImplant or Graft; Rejection
-
Cairo UniversityCompletedImplant or Graft; RejectionEgypt
-
PlexisionMedical University of South CarolinaUnknownAntibody-Mediated Graft RejectionUnited States
-
NovartisCompletedKidney Transplantation | Graft RejectionUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States