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Fabry DiseasePhase 3NCT01298141

A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease

A Phase 3 study testing agalsidase alfa in people with Fabry Disease, run by Shire at 12 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to observe the safety of agalsidase alfa in Canadian patients with Fabry disease. Read more about this study

Who is it for?
Any age
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
171 participants
Where
12 sitesCanada
Study dates
10 Aug 2011to 25 Sep 2017
Phase
Phase 3
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Cohort 1:
  • The patient has a documented diagnosis of Fabry disease.
  • The patient is sufficiently compliant with study activities to participate in this treatment plan, as judged by the Investigator.
  • The patient must meet current Canadian guidelines for enzyme replacement therapy for Fabry disease by meeting one of the following criteria:
  • Age-adjusted glomerular filtration rate (GFR) <80 ml/min or a decline in GFR of >10% which is sustained for 3 months and for which other causes of declining renal function have been excluded by a nephrologist or any 2 of the following:
  • Isolated proteinuria ≥500 mg/day/1.73 m2 without other cause
Show all 26Show fewer
  • Nephrogenic diabetes insipidus
  • Fanconi syndrome
  • Hypertension
  • Evidence of cardiac involvement related to Fabry disease including any 2 of the following:
  • Left ventricular (LV) wall thickness >12 mm
  • Left ventricular hypertrophy (LVH) by electrocardiogram (ECG); Estes ECG score must be >5
  • Left ventricular mass index (LVMI) by 2D echocardiogram 20% above normal for age
  • Diastolic filling abnormalities by 2D echocardiogram or by other accepted measures of diastolic filling. E/A ration >2.0 and deceleration time <140 msec
  • Increase of LV mass of at least 5 g/m2/year, with three measurements over a minimum of 12 months
  • Increase of left atrium (LA) size on 2D echo at least 10% above normal for age. In parasternal long axis view (PLAX) >33 mm; in four chamber view >42 mm
  • Cardiac conduction and rhythm abnormalities: atrioventricular (AV) block, short PR interval, left branch bundle block (LBBB), ventricular or atrial tachyarrhythmias, sinus bradycardia (in the absence of drugs with negative chronotropic activity)
  • Delayed posterolateral left ventricular wall late enhancement on MRI as evidence of advanced cardiac disease with fibrosis
  • Evidence of neurological involvement related to Fabry disease including 1 of the following:
  • Stroke or transient ischemic attack (TIA) prior to the age of 55 documented by a neurologist
  • Acute onset unilateral hearing loss
  • Acut monocular visual loss without other cause
  • Chronic, intractable diarrhea and/or abdominal pain/cramps, refractory to standard management for at least 6 months.
  • Chronic, intractable neuropathic pain, refractory to analgesics and standard pain management for at least 6 months.
  • Cohort 2:
  • Patient must have participated in Study REP001a.

Who cannot join

  • The patient has experienced an anaphylactic or anaphylactoid reaction or other infusion-related reaction which, in the opinion of the Investigator, precludes further treatment with agalsidase alfa or may interfere with the interpretation of the study.
  • The patient is otherwise unsuitable for the study, in the opinion of the Investigator.
  • The patient is enrolled in another clinical study, other than the Canadian Fabry Disease Initiative (CFDI).

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Canada12 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3B 6A8

  • University of Alberta Hospital

    Edmonton, Alberta, T6G 2H7

  • Queen Elizabeth II Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V8

  • Izaak Walton Killam (IWK) Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • Kingston General Hospital

    Kingston, Ontario, K7L 3J6

  • London Health Sciences Centre - Victoria Hospital

    London, Ontario, N6C 2V5

  • Hopital du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Centre Hospitalier Universitaire de Sherbrooke (CHUS)

    Sherbrooke, Quebec, J1H 5N4

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • The Fred A. Litwin Family Centre in Genetic Medicine

    Toronto, Ontario, M5T 3L9

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

  • University of Manitoba

    Winnipeg, Manitoba, R3A 1S1

Other trials in Canada

About this study

Official title: A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal® (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease

The purpose of this study is to observe the safety of agalsidase alfa in Canadian patients with Fabry disease.

Read the detailed description

This study will evaluate the safety of agalsidase alfa in patients with Fabry disease.

Patients diagnosed with Fabry disease who meet current Canadian guidelines for enzyme replacement therapy will be eligible to enroll in the study and will receive agalsidase alfa at a dose of 0.2 mg/kg body weight administered by an IV infusion over 40 minutes every week or every other week, based on previous treatment.

Shire has implemented a change to the drug substance manufacturing process. Safety data will be collected in patients receiving product manufactured with this process. There are no changes to the drug product formulation, manufacturing site, manufacturing process, and container closure.

Conditions
Fabry Disease
Being tested
agalsidase alfa
Keywords
Replagal, Enzyme Replacement Therapy, agalsidase alfa
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

    Cohort 1: 0.2 mg/kg body weight administered as an intravenous (IV) infusion over 40 minutes every other week (EOW)

    Cohort 2: 0.2 mg/kg body weight administered as an intravenous (IV) infusion over 40 minutes weekly

Study groups in NCT01298141
Study groupRoleWhat they receive
Replagal®ExperimentalAll eligible patients may receive Replagal produced by the bioreactor process (AF Replagal) on this treatment plan until AF Replagal is commercially available for the patient, the patient's participation is discontinued, or the study is discontinued, whichever comes first.
Receives: Biological: agalsidase alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.Treatment-emergent adverse events (TEAEs) were defined as those events which occurred or worsened in severity after first treatment with Replagal AF until 30 days after the last dose. A serious AE (SAE) was any AE occurred at any dose that resulted in death, life-threatening, hospitalization, prolongation of existing hospitalization, persistent or significant disability or incapacity and congenital anomaly or birth defect.

    Measured: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)

  2. Number of Participants With Infusion-Related Reactions (IRR)

    An IRR (also referred to as infusion-related adverse event [IRAE]) was defined as an AE that began either during the infusion or within 12 hours after the start of the infusion and was judged as possibly or probably related to study drug. The IRRs were classified based on the severity as Mild=No limitation of usual activities, Moderate=Some limitation of usual activities, Severe=Inability to carry out usual activities and Life-threatening=Immediate risk of death. The number of participants with infusion-related reactions was reported.

    Measured: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)

  3. Number of Participants Who Reported Positive to Immunoglobulin A (IgA)

    The IgA status was measured using enzyme-linked immunosorbent assay (ELISA). Number of participants who reported positive to IgA was reported.

    Measured: Baseline (within 6 months prior to first dose) up to Week 129

  4. Number of Participants Who Reported Positive to Immunoglobulin E (IgE)

    The IgE status was measured using ELISA. Number of participants who reported positive to IgE was reported.

    Measured: Baseline (within 6 months prior to first dose) up to Week 129

  5. Number of Participants Who Reported Positive to Immunoglobulin M (IgM)

    The IgM status was measured using ELISA. Number of participants who reported positive to IgM was reported.

    Measured: Baseline (within 6 months prior to first dose) up to Week 129

  6. Number of Participants Who Reported Positive to Anti-drug Antibody (ADA)

    The ADA status was measured using ELISA and electrochemiluminescent (ECL) immunoassay. Number of participants who reported positive to ADA was reported.

    Measured: Baseline (within 6 months prior to first dose) up to Week 285

  7. Number of Participants Who Reported Positive to Neutralizing Antibody (NAb)

    The NAb status was measured using enzyme activity inhibition assay. Number of participants who reported positive to NAb was reported.

    Measured: Baseline (within 6 months prior to first dose) up to Week 285

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2011 (estimated)
  2. Study start10 Aug 2011
  3. Primary completion25 Sep 2017
  4. Study completion25 Sep 2017

Resources

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 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
171 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01298141
Sponsor's protocol ID
HGT-REP-081
Status last verified
May 2021
First submitted
15 Feb 2011
Last updated
8 Jun 2021
Data monitoring committee
Yes

Publications

  • Khan A, Sirrs SM, Bichet DG, Morel CF, Tocoian A, Lan L, West ML; Canadian Fabry Disease Initiative. The Safety of Agalsidase Alfa Enzyme Replacement Therapy in Canadian Patients with Fabry Disease Following Implementation of a Bioreactor Process. Drugs R D. 2021 Dec;21(4):385-397. doi: 10.1007/s40268-021-00361-4. Epub 2021 Sep 20.

    PubMed 34542871

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing agalsidase alfa in people with Fabry Disease, run by Shire at 12 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 26 inclusion and 3 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 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 15 Feb 2019). 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?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01298141, which also lists 1 linked publication.

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 8 Jun 2021.

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