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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01304277
First received: February 15, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Fabry Disease
Biological: agalsidase alfa
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels [ Time Frame: Baseline to EOS ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels [ Time Frame: Baseline to EOS ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose) [ Time Frame: Week 0 to Week 14 ] [ Designated as safety issue: No ]
  • Dose-normalized Maximum Serum Concentration (Cmax/Dose) [ Time Frame: Week 0 to Week 14 ] [ Designated as safety issue: No ]
  • To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study [ Time Frame: EOS ] [ Designated as safety issue: Yes ]
  • Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF) [ Time Frame: Week 2 to EOS ] [ Designated as safety issue: Yes ]
    To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.


Enrollment: 17
Study Start Date: March 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01304277

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: Anna Wijatyk, MD Shire Human Genetic Therapies, Inc.
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01304277     History of Changes
Other Study ID Numbers: HGT-REP-082
Study First Received: February 15, 2011
Results First Received: December 30, 2013
Last Updated: March 25, 2014
Health Authority: Canada: Health Canada

Keywords provided by 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

ClinicalTrials.gov processed this record on August 27, 2014