Back to resultsA Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fabrazyme (agalsidase beta)
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring alpha Galactosidase A, aGAL, rh aGAL, Fabry, GL3, Fabrazyme
Eligibility Criteria
Inclusion Criteria: Have clinical manifestations of Fabry disease All patients have to have a plasma αGAL activity of < 1.5 nmol/hr/mL or a documented leukocyte αGAL activity of < 4 nmol/hr/mg Patient or patient's parent/guardian had to provide written informed consent prior to any study-related procedures being performed Patients had to be male and ≥ 16 years of age Exclusion Criteria: There is evidence of renal insufficiency, as defined by serum creatinine greater than or equal to 2.2 mg/dL (194.7 μmol/L) AND/OR has an estimated glomerular filtration rate (GFR) of <80 mL/min (using the equation derived from the Modification of Diet in Renal Disease Study (MDRD)) Has undergone kidney transplantation or is currently on dialysis Has a clinically significant organic disease or an unstable condition (with the exception of symptoms relating to Fabry disease) that in the opinion of the Investigator would preclude participation in the trial Has participated in a study employing an investigational drug within 30 days of the start of this trial Patients who received prior treatment with enzyme replacement therapy for Fabry disease Patient was unable to comply with the requirements of the protocol
Sites / Locations
- II. interní klinika 1. LF UK
- Tartu University Clinics, Department of Internal Medicine
- Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
- Detská fakultná nemocnica Kramáre I. Interná klinika
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fabrazyme
Arm Description
Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Outcomes
Primary Outcome Measures
Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Secondary Outcome Measures
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Skin biopsies were taken at Baseline, Week 24, Week 48, Week 72, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Estimated Glomerular Filtration Rate (eGFR)
Evaluated at Baseline, Week 24 and Week 96. eGFR is an estimation of the glomerular filtration rate of the kidneys (how much blood the kidneys are filtering). For this study, normal eGFR was defined as greater than 90 mL/min/1.73 m2
Plasma Globotriaosylceramide (GL-3)
Evaluated at Baseline, Week 24, Week 48, Week 72 and Week 96. Plasma GL-3 is often elevated in the plasma of patients diagnosed with Fabry disease. This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level was <= 7.03 µg/mL.
Urine Globotriaosylceramide (GL-3)
Evaluated at Baseline, Week 24 and Week 96. Urine GL-3 is often elevated in the urine of patients diagnosed with Fabry disease. This outcome measure evaluated the mean urine GL-3 in first morning void urine for all patients to see if it decreased while on Fabrazyme. Normal Urine GL-3 threshold was < 8.8 μg/mg.
Full Information
NCT ID
NCT00196716
First Posted
September 12, 2005
Last Updated
March 17, 2015
Sponsor
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT00196716
Brief Title
A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
Official Title
A Multicenter, Open-label Study of Low Dose Maintenance Treatment of Fabrazyme (Recombinant Human Alpha-Galactosidase A (R-h Alpha-GAL)) Replacement Therapy in Patients With Fabry Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
March 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
5. Study Description
Brief Summary
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the alpha-galactosidase A enzyme. This enzyme helps to break down and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In people with Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because alpha-galactosidase A is not present, or is present in small quantities. The build up of glycolipid levels (also referred to as "globotriaosylceramide" or "GL-3") in these tissues is thought to cause the clinical symptoms that are common to Fabry disease. Symptoms commonly appear during childhood with pain in the hands and feet. This trial is designed to evaluate the efficacy of a lower dose of Fabrazyme in patients who initially received 1.0 mg/kg every 2 weeks of Fabrazyme by investigating if the achieved clearance of glycosphingolipid deposits in the vascular endothelium of the kidney can be maintained at a lower dose.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
alpha Galactosidase A, aGAL, rh aGAL, Fabry, GL3, Fabrazyme
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fabrazyme
Arm Type
Experimental
Arm Description
Open-label study. Patients received 1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months.
Intervention Type
Biological
Intervention Name(s)
Fabrazyme (agalsidase beta)
Other Intervention Name(s)
r-hαGAL
Intervention Description
1.0 mg/kg Fabrazyme every two weeks for approximately six months followed by 0.3 mg/kg Fabrazyme every two weeks for approximately 18 months
Primary Outcome Measure Information:
Title
Globotriaosylceramide (GL-3) Clearance in Kidney Interstitial Capillary Endothelium
Description
Kidney biopsies were taken at Baseline, Week 24, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Time Frame
Throughout study; 96 weeks
Secondary Outcome Measure Information:
Title
Skin Globotriaosylceramide (GL-3) Clearance From Superficial Skin Capillary Endothelium
Description
Skin biopsies were taken at Baseline, Week 24, Week 48, Week 72, and Week 96 and analyzed for cellular GL-3 accumulation (inclusions) by light microscopy. Each biopsy was evaluated by pathologists for the total number of vessels with GL-3 accumulation on an inclusion severity score of 0 (none/trace), 1 (mild), 2 (moderate), and 3 (severe).
Time Frame
Throughout study ; 96 weeks
Title
Estimated Glomerular Filtration Rate (eGFR)
Description
Evaluated at Baseline, Week 24 and Week 96. eGFR is an estimation of the glomerular filtration rate of the kidneys (how much blood the kidneys are filtering). For this study, normal eGFR was defined as greater than 90 mL/min/1.73 m2
Time Frame
Throughout study; 96 weeks
Title
Plasma Globotriaosylceramide (GL-3)
Description
Evaluated at Baseline, Week 24, Week 48, Week 72 and Week 96. Plasma GL-3 is often elevated in the plasma of patients diagnosed with Fabry disease. This outcome measure evaluated the mean plasma GL-3 values for all patients to see if it decreased while on Fabrazyme. Normal plasma GL-3 level was <= 7.03 µg/mL.
Time Frame
Throughout study; 96 weeks
Title
Urine Globotriaosylceramide (GL-3)
Description
Evaluated at Baseline, Week 24 and Week 96. Urine GL-3 is often elevated in the urine of patients diagnosed with Fabry disease. This outcome measure evaluated the mean urine GL-3 in first morning void urine for all patients to see if it decreased while on Fabrazyme. Normal Urine GL-3 threshold was < 8.8 μg/mg.
Time Frame
Throughout study, 96 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have clinical manifestations of Fabry disease
All patients have to have a plasma αGAL activity of < 1.5 nmol/hr/mL or a documented leukocyte αGAL activity of < 4 nmol/hr/mg
Patient or patient's parent/guardian had to provide written informed consent prior to any study-related procedures being performed
Patients had to be male and ≥ 16 years of age
Exclusion Criteria:
There is evidence of renal insufficiency, as defined by serum creatinine greater than or equal to 2.2 mg/dL (194.7 μmol/L) AND/OR has an estimated glomerular filtration rate (GFR) of <80 mL/min (using the equation derived from the Modification of Diet in Renal Disease Study (MDRD))
Has undergone kidney transplantation or is currently on dialysis
Has a clinically significant organic disease or an unstable condition (with the exception of symptoms relating to Fabry disease) that in the opinion of the Investigator would preclude participation in the trial
Has participated in a study employing an investigational drug within 30 days of the start of this trial
Patients who received prior treatment with enzyme replacement therapy for Fabry disease
Patient was unable to comply with the requirements of the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
II. interní klinika 1. LF UK
City
Praha 2
ZIP/Postal Code
128 02
Country
Czech Republic
Facility Name
Tartu University Clinics, Department of Internal Medicine
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Klinika Chorob Metabolicznych, Instytut "Pomnik-Centrum Zdrowia Dziecka"
City
Warsaw
ZIP/Postal Code
04-736
Country
Poland
Facility Name
Detská fakultná nemocnica Kramáre I. Interná klinika
City
Bratislava 37
ZIP/Postal Code
833 40
Country
Slovakia
12. IPD Sharing Statement
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A Study of the Safety and Efficacy of Fabrazyme in Patients With Fabry Disease
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