Dosing Study of Replagal in Patients With Fabry Disease
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: Replagal
Intervention description: enzyme replacement therapy
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: Male
Healthy volunteers: No
Keywords: Lysosomal Storage; Renal Insufficiency; Stroke; Hypohidrosis; Peripheral Neuropathy; Fabry Disease

Summary:

      This study will determine the safety and effectiveness of increasing Replagal infusions in
      certain patients with Fabry disease. Replagal is a genetically engineered form of
      Alpha-galactosidase A, an enzyme that normally breaks down a fatty substance called
      globotriaosylceramide (Gb3). In patients with Fabry disease, Alpha-galactosidase A does not
      function properly and, therefore, Gb3 builds up, causing problems with the kidneys, heart,
      nerves, and blood vessels.

      Patients with Fabry disease who are participating in NIH protocol 00-N-0185 or 02-N-0220 may
      be eligible for this study. This includes patients who are currently taking Replagal but
      whose kidney function continues to worsen, or patients who have certain test results that are
      much improved after Replagal infusion.

      Participants will receive Replagal infusions (0.2 mg/kg body weight) through a vein once a
      week (as opposed to the previous dosage of once every 2 weeks) for up to 2 years. The first
      infusion, and some others, are given at the NIH Clinical Center, but most are administered by
      the patient's local doctor. Vital signs are measured before, immediately after, and 1 hour
      after each infusion.

      Baseline evaluations are done on an inpatient basis at the NIH Clinical Center over a 1-week
      period before and after the first Replagal infusion and at 6-month intervals during the
      study. Tests include a check of vital signs (temperature, respiratory rate, pulse rate, and
      blood pressure); weight measurement; physical and neurological examinations; routine blood
      and urine tests; 24-hour urine collection; electrocardiogram; and review of treatment side
      effects. In addition, the following tests are done:

        -  Quantitative sensory testing: This is a non-invasive test to measure the ability to
           sense warm, cold and vibration in the hand and foot.

        -  QSART: This test measures the amount of sweat in a particular area of skin that did not
           sweat enough. A small amount of a medicine called acetylcholine is put on the skin and
           made to enter the skin using a very small electric current.

        -  Doppler skin blood flow: This test measures blood flow to the blood vessels of the skin.
           A machine takes pictures of blood flow in the skin of the forearm using a laser beam.
           Pictures are taken before and during application of medicines that cause blood vessels
           to dilate. Acetylcholine is used on one forearm and nitroprusside is used on the other.
           The medication is made to enter the skin using a small el...
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients with Fabry disease participating in 00-N-0185/TKT011 or 02-N-0220/TKT015 may be
        eligible. No other Fabry patients will be eligible.

        Patients losing GFR at a rate greater than 5 ml/min/year despite ERT with agalsidase alfa
        for greater than or equal to 2.5 years in 00-N-0185/TKT/003/006/011 Study or ERT over
        greater than or equal to 1.0 years in 02-N-0220/TKT/010/015 Study.

        Patients who at least twice demonstrated significant improvement or normalization of sweat
        function (by QSART or thermoregulatory sweat test) or reduction in serum creatinine by at
        least 10% but return to the pre-infusion state before the subsequent biweekly enzyme
        infusion.

        Patients who freely agree to participate in this study and understand the nature, risks and
        benefits of this study and give their written informed consent.

        EXCLUSION CRITERIA:

        Patients with Fabry disease, who are not already part of 00-N-0185/TKT011 or
        02-N-0220/TKT015.

        Patients on these protocols who have stable serum creatinine (or a lesser rise in serum
        creatinine than stipulated in the inclusion criteria), and do not show other objective
        evidence of incomplete clinical response between biweekly infusions (e.g. sweat function).

        Patients who have begun dialysis or who have received a renal transplant.

        Patients who cannot tolerate the study procedures or who are unable or unwilling to travel
        to the study center as required by this protocol.

        Patients with an intercurrent medical condition that would render them unsuitable for mthe
        study e.g. HIV, diabetes. The reason is that the pathologies of these conditions will be
        significant confounders in assessing the effect of the experimental therapy and its adverse
        events.

        Patients who in the opinion of the investigator (for whatever reason) are thought to be
        unsuitable for the study.