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

NCT01298141 | Completed Phase 3 Results DMC

• 1 other identifier: HGT-REP-081
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

Fabry Disease

Keywords

Replagal; Enzyme Replacement Therapy; agalsidase alfa

Outcome Measures

Primary Outcomes (7)

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

Study Arms (1)

Replagal®

EXPERIMENTAL

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.

Biological: agalsidase alfa

Interventions

agalsidase alfa 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

Also known as: Replagal

Replagal®

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Shire: lead

Study Sites (12)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2H7, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3A 1S1, Canada

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 1V8, Canada

Location

Izaak Walton Killam (IWK) Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 3J6, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6C 2V5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

The Fred A. Litwin Family Centre in Genetic Medicine

Toronto, Ontario, M5T 3L9, Canada

Location

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• 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.

  PMID: 34542871 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

agalsidase alfa

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2011
• First Posted: February 17, 2011
• Study Start: August 10, 2011
• Primary Completion: September 25, 2017
• Study Completion: September 25, 2017
• Last Updated: June 8, 2021
• Results First Posted: February 15, 2019

Record last verified: 2021-05

Locations

CA (12)