Dosing Study of Replagal in Patients With Fabry Disease

NCT00068107 | Completed Phase 2 Results

• 2 other identifiers: 03028603-N-0286
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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...

Conditions

Fabry Disease

Keywords

Lysosomal Storage; Renal Insufficiency; Stroke; Hypohidrosis; Peripheral Neuropathy; Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Estimated Glomerular Filtration Rate (eGFR)

  The rate of decline in renal function, as measured by estimation of glomerular filtration rate at baseline when participants were receiving agalsidase alfa (Relagal) every 2 weeks and when participants were receiving weekly infusion of Relagal.

  Relagal was administered every 2 weeks for 2-4 years pre-study, Relagal was administred weekly during the study (approx. 4.5-10 years)

Secondary Outcomes (5)

• Globotriaosylceramide (Gb(3)) in Plasma

  Baseline and last observation (up to 10 years)

• Globotriaosylceramide (Gb(3)) in Urine Sediment

  Baseline and last observation (up to 10 years)

• Number of Participants With a Change in Quantitative Sudomotor Axon Reflex Test

  Baseline and last observation (up to 10 years)

• Quantitative Sensory Testing

  pre-study was 2-4 years, during study sensory testing measured for approx. 4.5-5 years

• Doppler Skin Blood Flow

  10 years

Study Arms (1)

Relagal

EXPERIMENTAL

All participants received Relagal administered weekly

Drug: Replagal

Interventions

Replagal DRUG

enzyme replacement therapy

Also known as: agalsidase alfa

Relagal

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Patients with Fabry disease, who are not already part of 00-N-0185/TKT011 or 02-N-0220/TKT015.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, Barton NW. Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Blood Cells Mol Dis. 2000 Aug;26(4):285-90. doi: 10.1006/bcmd.2000.0310.

  PMID: 11042029 BACKGROUND

• Brady RO. Enzymatic abnormalities in diseases of sphingolipid metabolism. Clin Chem. 1967 Jul;13(7):565-77. No abstract available.

  PMID: 5006481 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

MeSH Terms

Conditions

Fabry Disease; Renal Insufficiency; Stroke; Hypohidrosis; Peripheral Nervous System Diseases

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; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sweat Gland Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuromuscular Diseases

Limitations and Caveats

Small number of subjects. Single group with comparison to baseline data.

Results Point of Contact

• Title: Dr. Raphael Schiffmann
• Organization: Baylor Research Institute

raphael.schiffmann@baylorhealth.edu

214-820-4533

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2003
• First Posted: September 8, 2003
• Study Start: September 1, 2003
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 31, 2015
• Results First Posted: March 31, 2015

Record last verified: 2015-03

Locations

US (1)