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NCT01298141

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

Completed Phase 3 Results posted Last updated 8 June 2021
What this trial tests

Phase 3 trial testing agalsidase alfa in Fabry Disease in 171 participants. Completed in 25 September 2017.

Timeline
10 August 2011
Primary endpoint
25 September 2017
25 September 2017

Quick facts

Lead sponsorShire
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment171
Start date10 August 2011
Primary completion25 September 2017
Estimated completion25 September 2017
Sites12 locations across Canada

Drugs / interventions tested

Conditions studied

Sponsor

Shire — full company profile →

Who can join

Eligibility, any sex, with Fabry Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)

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 ex

Any TEAE
GroupValue95% CI
Replagal (Agalsidase Alfa)163
Any Serious TEAE
GroupValue95% CI
Replagal (Agalsidase Alfa)74
Any TEAE Leading to Treatment Discontinuation
GroupValue95% CI
Replagal (Agalsidase Alfa)7
Number of Participants With Infusion-Related Reactions (IRR) Primary · From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)

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.

Mild
GroupValue95% CI
Replagal (Agalsidase Alfa)21
Moderate
GroupValue95% CI
Replagal (Agalsidase Alfa)16
Severe
GroupValue95% CI
Replagal (Agalsidase Alfa)3
Life-threatening
GroupValue95% CI
Replagal (Agalsidase Alfa)0
Number of Participants Who Reported Positive to Immunoglobulin A (IgA) Primary · Baseline (within 6 months prior to first dose) up to Week 129

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

GroupValue95% CI
Replagal (Agalsidase Alfa)10
Number of Participants Who Reported Positive to Immunoglobulin E (IgE) Primary · Baseline (within 6 months prior to first dose) up to Week 129

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

GroupValue95% CI
Replagal (Agalsidase Alfa)1
Number of Participants Who Reported Positive to Immunoglobulin M (IgM) Primary · Baseline (within 6 months prior to first dose) up to Week 129

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

GroupValue95% CI
Replagal (Agalsidase Alfa)48
Number of Participants Who Reported Positive to Anti-drug Antibody (ADA) Primary · Baseline (within 6 months prior to first dose) up to Week 285

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

GroupValue95% CI
Replagal (Agalsidase Alfa)42
Number of Participants Who Reported Positive to Neutralizing Antibody (NAb) Primary · Baseline (within 6 months prior to first dose) up to Week 285

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

GroupValue95% CI
Replagal (Agalsidase Alfa)27

Adverse events — posted to ClinicalTrials.gov

Time frame: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Replagal (Agalsidase Alfa)
Serious: 74/167 (44%)
Deaths: 6/167

Serious adverse events (155 terms)

ReactionSystemReplagal (Agalsidase Alfa)
Renal failure chronicRenal and urinary disorders
Cerebrovascular accidentNervous system disorders
Myocardial infarctionCardiac disorders
Ventricular tachycardiaCardiac disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
Renal failure acuteRenal and urinary disorders
Angina pectorisCardiac disorders
AnaemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Acute coronary syndromeCardiac disorders
Cardiac failure congestiveCardiac disorders
DysphagiaGastrointestinal disorders
Fabry's diseaseCongenital, familial and genetic disorders
Acute myocardial infarctionCardiac disorders
DehydrationMetabolism and nutrition disorders
SyncopeNervous system disorders
Transient ischaemic attackNervous system disorders
ConstipationGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
NauseaGastrointestinal disorders
PancreatitisGastrointestinal disorders
Paraesthesia oralGastrointestinal disorders
Umbilical herniaGastrointestinal disorders
Chest painGeneral disorders
Other adverse events (82 terms — click to expand)

ReactionSystemReplagal (Agalsidase Alfa)
FatigueGeneral disorders
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
Oedema peripheralGeneral disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PalpitationsCardiac disorders
Pain in extremityMusculoskeletal and connective tissue disorders
NeuralgiaNervous system disorders
InfluenzaInfections and infestations
Abdominal painGastrointestinal disorders
ParaesthesiaNervous system disorders
PyrexiaGeneral disorders
HypoaesthesiaNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
VertigoEar and labyrinth disorders
Non-Cardiac chest painGeneral disorders
Urinary tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
Angina pectorisCardiac disorders
MyalgiaMusculoskeletal and connective tissue disorders
ContusionInjury, poisoning and procedural complications
Lower respiratory tract infectionInfections and infestations
AnxietyPsychiatric disorders
HyperhidrosisSkin and subcutaneous tissue disorders
BronchitisInfections and infestations
RashSkin and subcutaneous tissue disorders
HypertensionVascular disorders
HypotensionVascular disorders
TinnitusEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
SinusitisInfections and infestations
TremorNervous system disorders

Most-reported serious reactions: Renal failure chronic, Cerebrovascular accident, Myocardial infarction, Ventricular tachycardia, Cellulitis, Pneumonia, Renal failure acute, Angina pectoris.

Data from ClinicalTrials.gov NCT01298141 adverse events section.

Sponsor's own description

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

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Role of lysosomes in physiological activities, diseases, and therapy.
    Zhang Z, Yue P, Lu T, Wang Y, et al · · 2021 · cited 238× · PMID 33990205 · DOI 10.1186/s13045-021-01087-1
  2. The Safety of Agalsidase Alfa Enzyme Replacement Therapy in Canadian Patients with Fabry Disease Following Implementation of a Bioreactor Process.
    Khan A, Sirrs SM, Bichet DG, Morel CF, et al · · 2021 · cited 2× · PMID 34542871 · DOI 10.1007/s40268-021-00361-4

Verify or expand the search:

Other trials of agalsidase alfa

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01298141.

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