Alternative Dosing and Regimen of Replagal to Treat Fabry Disease

NCT00075244 | Completed Phase 2

• 2 other identifiers: 04007304-N-0073
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to assess the pharmacodynamic effects of different or more frequent doses of Replagal compared to the standard dosing regimen. Replagal is a genetically engineered form of alpha-Galactosidase A, an enzyme that normally breaks down a fatty substance called globotriaosylceramide (Gb(3)). In patients with Fabry disease, GB(3) does not function properly and therefore builds up causing problems with the kidneys, heart, nerves, and blood vessels. Male patients 18 years of age or older with Fabry disease who are not on dialysis and have not received a kidney transplant may be eligible for this study. Participants are randomly assigned to receive one of the following five regimens of Replagal infusions, given through a vein over 20 to 80 minutes: 0.1 mg/kg body weight every week 0.2 mg/kg body weight every week 0.2 mg/kg body weight every other week 0.4 mg/kg body weight every week 0.4 mg/kg body wieght every other week In the US, the infusions are given at the NIH Clinical Center. Vital signs are measured before, immediately after, and 1 hour after each infusion. Baseline evaluations are done on an inpatient or outpatient basis. Baseline tests include a check of vital signs (temperature, respiratory rate, pulse rate, and blood pressure); physical examination; laboratory tests; and review of treatment side effects. Evaluations are also done at every infusion visit, and 1 week and 1 month after the last infusion. Safety evaluations are done periodically and include vital sign measurements, physical examination, blood and urine tests, review of drug side effects, electrocardiogram (ECG), Holder monitor (2 hour ECG), and QSART (NIH only). The QSART (quantitative sudomotor axon reflex test) measures the amount of sweat in a particular area of skin, mostly the forearm. For this test, a cup partly filled with a liquid is strapped on the arm. A weak electric current is turned on, stimulating the sweat glands, and the amount of sweat produced is measured. There is a tingling sensation when the current is turned on. Patients who complete the study will be offered the opportunity of receiving Replagal for 6 months in an extension study.

Conditions

Fabry Disease

Keywords

Lysosomes; Storage; Glycolipid; Fabry Disease; Stroke

Interventions

Replagal DRUG

Eligibility Criteria

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

You may qualify if:

• Subject is a male hemizygote, age 18 years or older, with confirmed diagnosis of Fabry Disease. Diagnosis of Fabry disease may be confirmed by proof of a mutation of the alpha-Galactosidase A gene compatible with Fabry Disease and/or a deficiency of alpha-Galactosidase A (less than 4.0 nmol/mL/hour in plasma or serum or less than 8% of average mean normal in leukocytes).
• Subject must have one or more clinical manifestations of Fabry disease including neuropathic pain, angiokeratoma, corneal verticillata, cardiomyopathy, hypo- or anhydrosis, abdominal pain and/or diarrhea, serum creatinine greater than 1.0 mg/dl or proteinuria greater than 300 mg/24 hours.
• Subject must have voluntarily signed an Institutional Review Board (IRB) approved informed consent form after all relevant aspects of the study have been explained and discussed with the subject.

You may not qualify if:

• Subject has been previously treated with Replagal or any other enzyme replacement therapy for Fabry Disease. If the patient has previously been treated with Replagal or another enzyme replacement therapy then they must have been off the therapy for at least 30 days and must have a Day-14 antibody blood sample drawn and that test must be negative for anti-agalsidase alfa IgG and IgE antibodies and not experienced a prior severe infusion reactions with prior enzyme replacement therapy.
• Subject has been enrolled in another clinical investigative study in the past 30 days.
• Subject is unable to give informed consent or is deemed unable to comply with all aspects of the clinical trial.
• Subject has plasma Gb(3) drawn on Day -14 less than 4.0 nmol/mL.
• Subject is undergoing dialysis or who has received a renal transplant.
• Subjects who cannot tolerate the study procedures or who are unable or unwilling to travel to the study center as required by this protocol.
• Subjects with an inter-current medical condition that would render them unsuitable for the study (e.g. HIV, diabetes) by confounding an assessment of the effects of the experimental therapy and its adverse events.
• Subjects who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163-7. doi: 10.1056/NEJM196705252762101. No abstract available.

  PMID: 6023233 BACKGROUND

• Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6;284(21):2771-5. doi: 10.1001/jama.284.21.2771.

  PMID: 11105184 BACKGROUND

• Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20;281(3):249-54. doi: 10.1001/jama.281.3.249.

  PMID: 9918480 BACKGROUND

MeSH Terms

Conditions

Fabry Disease; Stroke

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 6, 2004
• First Posted: January 7, 2004
• Study Start: January 1, 2004
• Study Completion: November 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-11

Locations

US (1)