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

Fabry Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01304277
• Other study ID #: HGT-REP-082
• Status: Completed
• Phase: Phase 2
• Start date: November 17, 2011
• Est. completion date: December 28, 2012

Study information

• Verified date: July 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 28, 2012
• Est. primary completion date: December 28, 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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 a-galactosidase A activity measured in serum, leukocytes, or fibroblasts or has a confirmed mutation of the a-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.

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• agalsidase alfa

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	INC Research	Toronto	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels		Baseline to EOS
Secondary	Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels		Baseline to EOS
Secondary	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
Secondary	Dose-normalized AUC Extrapolated to Infinity (AUC8/Dose)	The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.	Week 0 to Week 14
Secondary	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
Secondary	To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study		EOS
Secondary	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