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

NCT ID: NCT01298141

Last Updated: 2021-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 171 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-10
• Study Completion Date: 2017-09-25

Brief Summary

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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Replagal®

All 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.

Group Type: EXPERIMENTAL

agalsidase alfa

Intervention Type: BIOLOGICAL

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

Interventions

agalsidase alfa

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Replagal

Eligibility Criteria

Inclusion Criteria

Cohort 1:

1. The patient has a documented diagnosis of Fabry disease.

2. The patient is sufficiently compliant with study activities to participate in this treatment plan, as judged by the Investigator.

3. The patient must meet current Canadian guidelines for enzyme replacement therapy for Fabry disease by meeting one of the following criteria:

1. 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
• Nephrogenic diabetes insipidus
• Fanconi syndrome
• Hypertension

2. 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

3. 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

4. Chronic, intractable diarrhea and/or abdominal pain/cramps, refractory to standard management for at least 6 months.

5. Chronic, intractable neuropathic pain, refractory to analgesics and standard pain management for at least 6 months.

Cohort 2:

4. Patient must have participated in Study REP001a.

Exclusion Criteria

1. 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.

2. The patient is otherwise unsuitable for the study, in the opinion of the Investigator.

3. The patient is enrolled in another clinical study, other than the Canadian Fabry Disease Initiative (CFDI).

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, Canada

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, Canada

Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

The Fred A. Litwin Family Centre in Genetic Medicine

Toronto, Ontario, Canada

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 34542871 (View on PubMed)

Provided Documents

Document Type: Study Protocol: Original Protocol

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Document Type: Study Protocol: Amendment 1

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Document Type: Study Protocol: Amendment 2

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Document Type: Study Protocol: Amendment 3

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Document Type: Study Protocol: Amendment 4

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Document Type: Study Protocol: Amendment 5

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Document Type: Statistical Analysis Plan

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Other Identifiers

HGT-REP-081

Identifier Type: -

Identifier Source: org_study_id