NIH Clinical Research Studies

Protocol Number: 04-N-0073

Active Accrual, Protocols Recruiting New Patients

Title:
A Phase I-II Pharmacokinetic/Pharmacodynamic Study of Replagal to Assess the Effects of Alternative Dose and Regimen in Patients with Fabry Disease
Number:
04-N-0073
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.

Sponsoring Institute:
National Institute of Neurological Disorders and Stroke (NINDS)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male
Referral Letter Required: No
Population Exclusion(s): Female

Children

Eligibility Criteria:
INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

Special Instructions:
Transkaryotic Therapies Inc.

Leanne Torrie, Manager, Patient Services

Telephone: 617-613-4499

Email: ltorrie@tktx.com

Study ID Number: TKT027

Other Locations and Contact Information:

Canada:

Queen Elizabeth II Health Sciences Centre

Halifax, NS B3H 1V8

Recruiting

Principal Investigator: Dr. Michael West

Study Contact Kaye Le Moine (902) 473-5770

University of Toronto

555 University Avenue

Toronto, Ontario

Recruiting

Principal Investigator: Dr. Joe Clarke

Study contact: Tracy Heeney (tracy.heeney@sickkids.ca)

416-813-7654 ext. 1455

Czech Republic:

2nd Department of Internal Medicine

1st School of Medicine

Charles University

Prague

Recruiting

Principal Investigator: Professor Jan Bultas

Contact Dr. Ales Linhart +420 (777) 287-930

Poland:

Szpital Uniwersytecki w Krakowie

Ul. Skawinska 8

31-066 Krakow

Recruiting

Principal Investigator: Professor Jacek Musial

Study Contact Dr. Anetta Undas +480 (607) 146-324

Klinika Kardiologii Ogolnej

Instytut Kardiologii

Ul. Alpejska 42

04-628 Warszawa

Recruiting

Principal Investigator/Study contact: Dr. Lidia Chojnowska +480 (272) 264-272

Keywords:
Lysosomes
Storage
Glycolipid
Fabry Disease
Stroke
Recruitment Keywords:
Fabry Disease
Conditions:
Fabry Disease
Investigational Drug(s):
Replagal
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Brady RO, et al. Enzymatic defect in Fabry's disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967 May 25;276(21):1163-7. No abstract available. PMID: 6023233

Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6;284(21):2771-5. Erratum in: JAMA 2001 Jan 10;285(2):169. PMID: 11105184

Meikle PJ, et al. Prevalence of lysosomal storage disorders. JAMA. 1999 Jan 20;281(3):249-54. PMID: 9918480

Active Accrual, Protocols Recruiting New Patients

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