Clinical trial NCT01298141: A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Replagal
Enzyme Replacement Therapy
agalsidase alfa
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-02-17
Enrollment: 171
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
measure: Number of Participants With Infusion-Related Reactions (IRR)
timeFrame: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
measure: Number of Participants Who Reported Positive to Immunoglobulin A (IgA)
timeFrame: Baseline (within 6 months prior to first dose) up to Week 129
measure: Number of Participants Who Reported Positive to Immunoglobulin E (IgE)
timeFrame: Baseline (within 6 months prior to first dose) up to Week 129
measure: Number of Participants Who Reported Positive to Immunoglobulin M (IgM)
timeFrame: Baseline (within 6 months prior to first dose) up to Week 129
measure: Number of Participants Who Reported Positive to Anti-drug Antibody (ADA)
timeFrame: Baseline (within 6 months prior to first dose) up to Week 285
measure: Number of Participants Who Reported Positive to Neutralizing Antibody (NAb)
timeFrame: Baseline (within 6 months prior to first dose) up to Week 285
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Halifax
country: Canada
facility: Izaak Walton Killam (IWK) Health Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: The Fred A. Litwin Family Centre in Genetic Medicine
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke (CHUS)
state: Quebec
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.