A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: agalsidase alfa
Intervention description: 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
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 171.0
Sex: All
Healthy volunteers: No
Keywords: Replagal; Enzyme Replacement Therapy; agalsidase alfa

Summary:

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

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).