This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.

A Phase II Comparability Study Between Replagal® Produced From Agalsidase Alfa Manufactured by 2 Different Processes in Adult Male Patients With Fabry Disease

This study is designed to evaluate safety and PK/PD in Canadian Fabry patients.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: agalsidase alfa

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2H7
      • University of Alberta Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V8
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M5V 2T3
      • INC Research
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. 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.
2. Patient is male and between 18 and 65 years of age, inclusive.
3. Patient must be willing to remain in the clinic as required by the study and comply with the procedures and evaluations of the study.
4. 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.
5. 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:

1. Patient is unable to be venipunctured and/or tolerate venous access.
2. Patient has tested positive for anti-agalsidase alfa antibodies either at screening or confirmation of eligibility visit.
3. Patient had pre-ERT plasma Gb3 levels within the normal range (if value is available).
4. Patient is participating in any other Shire HGT investigational study.
5. 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.
6. 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.
7. 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.
8. The patient has previously received AF Replagal prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Replagal® (0.2 mg/kg, IV, EOW); 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	Biological: agalsidase alfa; Other Names: Replagal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels	Baseline to EOS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels		Baseline to EOS
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.	Week 0 to Week 14
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)	The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.	Week 0 to Week 14
Dose-normalized Maximum Serum Concentration (Cmax/Dose)	The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.	Week 0 to Week 14
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study		EOS
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.	Week 2 to EOS

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2011
• Primary Completion (Actual): December 28, 2012
• Study Completion (Actual): December 28, 2012

Study Registration Dates

• First Submitted: February 15, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimate): February 25, 2011

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Replagal
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: HGT-REP-082