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

• ClinicalTrials.gov Identifier: NCT01304277
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Results First Posted: April 25, 2014
• Last Update Posted: July 19, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Biological: agalsidase alfa	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: November 17, 2011
• Actual Primary Completion Date: December 28, 2012
• Actual Study Completion Date: December 28, 2012

Arms and Interventions

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 Name: Replagal

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels [ Time Frame: Baseline to EOS ]

Secondary Outcome Measures :

1. Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels [ Time Frame: Baseline to EOS ]
2. Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose) [ Time Frame: Week 0 to Week 14 ]
   The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
3. Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose) [ Time Frame: Week 0 to Week 14 ]
   The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
4. Dose-normalized Maximum Serum Concentration (Cmax/Dose) [ Time Frame: Week 0 to Week 14 ]
   The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
5. To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study [ Time Frame: EOS ]
6. Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF) [ Time Frame: Week 2 to EOS ]
   To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Canada, Alberta

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2H7

Canada, Nova Scotia

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada, B3H 1V8

Canada, Ontario

The Hospital for Sick Children

Toronto, Ontario, Canada, M5G 1X8

INC Research

Toronto, Ontario, Canada, M5V 2T3

Canada, Quebec

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada, H4J 1C5

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01304277
• Other Study ID Numbers: HGT-REP-082
• First Posted: February 25, 2011
• Results First Posted: April 25, 2014
• Last Update Posted: July 19, 2021
• Last Verified: July 2021

Keywords provided by Takeda ( Shire ):

Replagal

Additional relevant MeSH terms:

Fabry Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders