Fabry DiseasePhase 2NCT01304277
This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.
A Phase 2 study testing agalsidase alfa in people with Fabry Disease, run by Shire at 5 sites in Canada.
Trial summary
This study is designed to evaluate safety and PK/PD in Canadian Fabry patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- agalsidase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 5 sitesCanada
- Study dates
- 17 Nov 2011to 28 Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Patient is male and between 18 and 65 years of age, inclusive.
- Patient must be willing to remain in the clinic as required by the study and comply with the procedures and evaluations of the study.
- 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.
- 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).
Who cannot join
- Patient is unable to be venipunctured and/or tolerate venous access.
- Patient has tested positive for anti-agalsidase alfa antibodies either at screening or confirmation of eligibility visit.
- Patient had pre-ERT plasma Gb3 levels within the normal range (if value is available).
- Patient is participating in any other Shire HGT investigational study.
- 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.
- 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.
- 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.
- The patient has previously received AF Replagal prior to study entry.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2H7
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 1V8
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, H4J 1C5
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
INC Research
Toronto, Ontario, M5V 2T3
About this study
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
This study is designed to evaluate safety and PK/PD in Canadian Fabry patients.
Read the 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.
- Conditions
- Fabry Disease
- Being tested
- agalsidase alfa
- Keywords
- Replagal
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
agalsidase alfaBiological
Also called Replagal
| Study group | Role | What they receive |
|---|---|---|
| Replagal® (0.2 mg/kg, IV, EOW) | Experimental | 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 Receives: Biological: agalsidase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
Measured: Baseline to EOS
Secondary outcomes (6)
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 0 to Week 14
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Measured: 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.
Measured: Week 2 to EOS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2011 (estimated)
- Study start17 Nov 2011
- Primary completion28 Dec 2012
- Study completion28 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01304277
- Sponsor's protocol ID
- HGT-REP-082
- Status last verified
- Jul 2021
- First submitted
- 15 Feb 2011
- Last updated
- 19 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01304277
- Acronym / sponsor ID
- HGT-REP-082
- Conditions
- Fabry Disease
- Keywords
- Replagal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2011 (actual)
- Primary completion
- 28 Dec 2012 (actual)
- Study completion
- 28 Dec 2012 (actual)
- First posted
- 25 Feb 2011 (estimated)
- Results
- Posted 25 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Replagal® (0.2 mg/kg, IV, EOW) | Experimental | Biological: agalsidase alfaScreening 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- Patient is male and between 18 and 65 years of age, inclusive.
- Patient must be willing to remain in the clinic as required by the study and comply with the procedures and evaluations of the study.
- 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.
- Patient provides informed consent.
Key exclusion criteria (8 listed)
- Patient is unable to be venipunctured and/or tolerate venous access.
- Patient has tested positive for anti-agalsidase alfa antibodies either at screening or confirmation of eligibility visit.
- Patient had pre-ERT plasma Gb3 levels within the normal range (if value is available).
- Patient is participating in any other Shire HGT investigational study.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| agalsidase alfaAlso: Replagal | Biological | Replagal® (0.2 mg/kg, IV, EOW) |
Primary outcome
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
Time frame: Baseline to EOS
6 secondary outcomes
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
Time frame: Baseline to EOS
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
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
Time frame: Week 0 to Week 14
Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Time frame: Week 0 to Week 14
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Time frame: EOS
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Time frame: Week 2 to EOS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing agalsidase alfa in people with Fabry Disease, run by Shire at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels (time frame: Baseline to EOS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2021.