Clinical trial NCT01304277: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fabry Disease
Keywords: Replagal
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-02-25
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility 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.

Primary outcomes:
measure: Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
timeFrame: Baseline to EOS
Secondary outcomes:
measure: Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
timeFrame: Baseline to EOS
measure: Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
timeFrame: Week 0 to Week 14
measure: Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
timeFrame: Week 0 to Week 14
measure: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
timeFrame: Week 0 to Week 14
measure: To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
timeFrame: EOS
measure: Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
timeFrame: Week 2 to EOS
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: INC Research
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: