Back to resultsThis Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
agalsidase alfa
Sponsored by
About this trial
This is an interventional other trial for Fabry Disease focused on measuring Replagal
Eligibility Criteria
Inclusion Criteria:
- The patient must be diagnosed with Fabry disease using the following criteria: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of α-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the α-galactosidase A gene.
- Patient is male and between 18 and 65 years of age, inclusive.
- Patient must be willing to remain in the clinic as required by the study and comply with the procedures and evaluations of the study.
- At the time of confirmation of study eligibility visit, patients must have received at least 26 weeks of treatment with RB Replagal at a dose of 0.2 mg/kg administered IV EOW.
- Patient provides informed consent.
Patients who are naive to ERT:
1. Treatment naive patients must have a pretreatment plasma Gb3 level above the normal range (if value is available).
Exclusion Criteria:
- Patient is unable to be venipunctured and/or tolerate venous access.
- Patient has tested positive for anti-agalsidase alfa antibodies either at screening or confirmation of eligibility visit.
- Patient had pre-ERT plasma Gb3 levels within the normal range (if value is available).
- Patient is participating in any other Shire HGT investigational study.
- Patient is currently on dialysis, is expected to begin dialysis during the study, has received a kidney transplant, or is on the renal transplant waiting list.
- Patient is unable to comply with the protocol (eg, clinical relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the Investigator, otherwise unsuited for the study.
- The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device), except for the Canadian Fabry Disease Initiative, within 6 months prior to receiving the first dose of AF Replagal in this study or at any time during the study.
- The patient has previously received AF Replagal prior to study entry.
Sites / Locations
- University of Alberta Hospital
- Queen Elizabeth II Health Sciences Centre
- The Hospital for Sick Children
- INC Research
- Hopital du Sacre-Coeur de Montreal
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Replagal® (0.2 mg/kg, IV, EOW)
Arm Description
Screening period of approximately 14 days during which all patients received 1 infusion of 0.2 mg/kg Replagal RB (Week 0) Treatment period of 14 weeks during which all patients received 7 infusions of 0.2 mg/kg Replagal AF
Outcomes
Primary Outcome Measures
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
Secondary Outcome Measures
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Dose-normalized Maximum Serum Concentration (Cmax/Dose)
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01304277
Brief Title
This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.
Official Title
A Phase II Comparability Study Between Replagal® Produced From Agalsidase Alfa Manufactured by 2 Different Processes in Adult Male Patients With Fabry Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
November 17, 2011 (Actual)
Primary Completion Date
December 28, 2012 (Actual)
Study Completion Date
December 28, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is designed to evaluate safety and PK/PD in Canadian Fabry patients.
Detailed Description
In 2008, a change in the agalsidase alfa drug substance manufacturing process was made. There are no changes to the drug product formulation, manufacturing site, manufacturing process, or container closure.
An agalsidase alfa bioreactor manufacturing process (agalAF1) utilizing animal component-free media replaced the previous roller bottle (RB) process.
This study is designed to provide PD/PK and safety data. The assessment schedule is designed to capture the PK profile of drug uptake in the blood as well the pharmacologic effect which manifests over the course of weeks. Each patient will serve as his own control.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Replagal
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Replagal® (0.2 mg/kg, IV, EOW)
Arm Type
Experimental
Arm Description
Screening period of approximately 14 days during which all patients received 1 infusion of 0.2 mg/kg Replagal RB (Week 0)
Treatment period of 14 weeks during which all patients received 7 infusions of 0.2 mg/kg Replagal AF
Intervention Type
Biological
Intervention Name(s)
agalsidase alfa
Other Intervention Name(s)
Replagal
Primary Outcome Measure Information:
Title
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
Time Frame
Baseline to EOS
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
Time Frame
Baseline to EOS
Title
Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
Description
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Time Frame
Week 0 to Week 14
Title
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
Description
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Time Frame
Week 0 to Week 14
Title
Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Description
The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Time Frame
Week 0 to Week 14
Title
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Time Frame
EOS
Title
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Description
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.
Time Frame
Week 2 to EOS
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient must be diagnosed with Fabry disease using the following criteria: The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of α-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the α-galactosidase A gene.
Patient is male and between 18 and 65 years of age, inclusive.
Patient must be willing to remain in the clinic as required by the study and comply with the procedures and evaluations of the study.
At the time of confirmation of study eligibility visit, patients must have received at least 26 weeks of treatment with RB Replagal at a dose of 0.2 mg/kg administered IV EOW.
Patient provides informed consent.
Patients who are naive to ERT:
1. Treatment naive patients must have a pretreatment plasma Gb3 level above the normal range (if value is available).
Exclusion Criteria:
Patient is unable to be venipunctured and/or tolerate venous access.
Patient has tested positive for anti-agalsidase alfa antibodies either at screening or confirmation of eligibility visit.
Patient had pre-ERT plasma Gb3 levels within the normal range (if value is available).
Patient is participating in any other Shire HGT investigational study.
Patient is currently on dialysis, is expected to begin dialysis during the study, has received a kidney transplant, or is on the renal transplant waiting list.
Patient is unable to comply with the protocol (eg, clinical relevant medical condition making implementation of the protocol difficult, unstable social situation, or otherwise unlikely to complete the study) or is, in the opinion of the Investigator, otherwise unsuited for the study.
The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or device), except for the Canadian Fabry Disease Initiative, within 6 months prior to receiving the first dose of AF Replagal in this study or at any time during the study.
The patient has previously received AF Replagal prior to study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2H7
Country
Canada
Facility Name
Queen Elizabeth II Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V8
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
INC Research
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5V 2T3
Country
Canada
Facility Name
Hopital du Sacre-Coeur de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4J 1C5
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.
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