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Dosing Study of Replagal in Patients With Fabry Disease

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ClinicalTrials.gov Identifier: NCT00068107
Recruitment Status : Completed
First Posted : September 8, 2003
Results First Posted : March 31, 2015
Last Update Posted : March 31, 2015
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Baylor Research Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Drug: Replagal
Enrollment 13
Recruitment Details 13 participants were recruited; 1 participant was excluded because of stable kidney function; 12 started treatment
Pre-assignment Details  
Arm/Group Title All Participants
Hide Arm/Group Description All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month. Patients will receive a dose of 0.2 mg/kg of body weight every week.
Period Title: Overall Study
Started 12
Completed 3
Not Completed 9
Reason Not Completed
end-stage renal disease             6
Death             2
Withdrawal by Subject             1
Arm/Group Title All Participants
Hide Arm/Group Description All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
<=18 years
0
   0.0%
Between 18 and 65 years
13
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants
41  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
0
   0.0%
Male
13
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants
13
1.Primary Outcome
Title Estimated Glomerular Filtration Rate (eGFR)
Hide Description 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.
Time Frame Relagal was administered every 2 weeks for 2-4 years pre-study, Relagal was administred weekly during the study (approx. 4.5-10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ml/min/month
eGFR on infusions every 2 wks -0.66  (0.24)
eGFR on infusions weekly -0.32  (0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Participants
Comments eGFR measured pre-study was compared to eGFR during the study
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Participants
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Average Delay in time to ESRD
Estimated Value 166
Confidence Interval (2-Sided) 95%
8.4 to 323.8
Estimation Comments The average delay in end stage renal disease (ESRD) calculated from the eGFR values and represents the estimated difference in time to ESRD between Relagal administered every 2 weeks and Relagal administered weekly. Units = months
2.Secondary Outcome
Title Globotriaosylceramide (Gb(3)) in Plasma
Hide Description [Not Specified]
Time Frame Baseline and last observation (up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants at Baseline All Participants at Last Observation
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
[Not Specified]
Overall Number of Participants Analyzed 11 11
Measure Type: Number
Unit of Measure: nanomole/mL
participant 1 2.35 4.10
participant 2 4.62 5.58
participant 3 2.43 2.62
participant 5 3.17 3.60
participant 6 6.78 5.04
participant 7 3.32 3.21
participant 8 3.69 4.51
participant 9 4.25 1.91
participant 10 2.59 3.41
participant 11 6.62 5.62
participant 12 6.56 6.63
3.Secondary Outcome
Title Globotriaosylceramide (Gb(3)) in Urine Sediment
Hide Description [Not Specified]
Time Frame Baseline and last observation (up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants at Baseline All Participants at Last Observation
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
[Not Specified]
Overall Number of Participants Analyzed 11 11
Measure Type: Number
Unit of Measure: nanomole/(gram of Creatinine)
participant 1 49 1888
participant 2 126 89
participant 3 248 82
participant 5 136 162
participant 6 3026 652
participant 7 3128 1682
participant 8 1393 450
participant 9 137 370
participant 10 1457 488
participant 11 2342 213
participant 12 624 169
4.Secondary Outcome
Title Number of Participants With a Change in Quantitative Sudomotor Axon Reflex Test
Hide Description Quantitative sudomotor axon reflex test (QSART) is a measure of sweat function
Time Frame Baseline and last observation (up to 10 years)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: participants
0
5.Secondary Outcome
Title Quantitative Sensory Testing
Hide Description For quantitative sensory testing, the outcome variable (detection threshold score) was analyzed for all combinations of location (foot, hand, and thigh) and test (cold, vibration, and warm). Possible threshold scores may range from 1-25. Score values of “>25” were set to 25. Higher scores indicate higher sensory detection threshold. Therefore, lower score is better. Time, measured in years, was centered at the date in which patients switched treatment regimen. All available measurements were used. A linear mixed model analysis was used to test for differences in the linear association between time and detection threshold score pre-and-post ERT regiment change while accounting for the correlation among observations from the same individual. Specifically, the model contained a subject specific random intercept with year as a fixed effect and knot at time of the treatment change.
Time Frame pre-study was 2-4 years, during study sensory testing measured for approx. 4.5-5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with a sufficient number of data points to estimate slope
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month. Patients will receive a dose of 0.2 mg/kg of body weight every week.
Overall Number of Participants Analyzed 10
Mean (Standard Error)
Unit of Measure: units on a scale/year
Cold Sensory testing on Foot (pre-study) -0.2108  (0.1366)
Cold Sensory on Foot (difference pre- to post-) 0.3863  (0.2784)
Vibration Sensory testing on Foot (pre-study) 0.3353  (0.1004)
Vibration on Foot (difference pre- to post-) -0.3912  (0.2041)
Warm Sensory testing on Foot (pre-study) -0.08536  (0.09264)
Warm on Foot (difference pre- to post-) 0.4169  (0.1887)
Cold Sensory testing on Hand (pre-study) -0.1026  (0.1413)
Cold on Hand (difference pre- to post-) 0.5141  (0.2874)
Vibration Sensory testing on Hand (pre-study) 0.2279  (0.07427)
Vibration on Hand (difference pre- to post-) -0.1966  (0.1503)
Warm Sensory testing on Hand (pre-study) -0.2138  (0.1179)
Warm on Hand (difference pre- to post-) 1.1781  (0.2401)
Cold Sensory testing on Thigh (pre-study) 0.2502  (0.1437)
Cold on Thigh (difference pre- to post-) -0.2991  (0.2884)
Warm Sensory testing on Thigh (pre-study) -0.549  (0.1124)
Warm on Thigh (difference pre- to post-) 0.8255  (0.2258)
6.Secondary Outcome
Title Doppler Skin Blood Flow
Hide Description [Not Specified]
Time Frame 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Doppler skin blood flow was not collected in this study because it was judged to not be useful early in the study.
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description All SAEs were adjudicated to be disease related and not related to the agalsidase alfa infusions.
 
Arm/Group Title All Participants
Hide Arm/Group Description All participants were followed on a prior protocol and found to have a mean slope on Replagal (agalsidase alfa) infused every 2 weeks of -0.66 +- 0.24 ml/min/month.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%)
Total   10/13 (76.92%) 
Cardiac disorders   
hypotension  1/13 (7.69%) 
myocardial infarction  1/13 (7.69%) 
syncopal episode [1]  1/13 (7.69%) 
elective mitral valve annuloplasty  1/13 (7.69%) 
shortness of breath  1/13 (7.69%) 
increased intensity of angina  1/13 (7.69%) 
aortic stenosis  1/13 (7.69%) 
ventricular tachycardia  1/13 (7.69%) 
recurrent ventricular arrhythmia  1/13 (7.69%) 
aortic valve replacement  1/13 (7.69%) 
dizziness, tachycardia and chest pain  1/13 (7.69%) 
clogged port-a-cath replacement and pacemaker adjustment  1/13 (7.69%) 
placement of a pacemaker due to a bradycardic episode  1/13 (7.69%) 
death  1/13 (7.69%) 
General disorders   
nausea and vomiting  1/13 (7.69%) 
Infections and infestations   
sepsis  1/13 (7.69%) 
bacterial sepsis  1/13 (7.69%) 
hepatitis C infection  1/13 (7.69%) 
Nervous system disorders   
Sharp chest pain and right leg pain  1/13 (7.69%) 
pain crisis  1/13 (7.69%) 
acute occipital ischemic stroke  1/13 (7.69%) 
Renal and urinary disorders   
catheter-induced peritonitis  1/13 (7.69%) 
advanced renal insufficiency  1/13 (7.69%) 
severe renal decline  1/13 (7.69%) 
[1]
occurred while straining when lifting weight in a gym
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
All Participants
Affected / at Risk (%)
Total   13/13 (100.00%) 
Blood and lymphatic system disorders   
Anemia  3/13 (23.08%) 
Ferritin - decreased  1/13 (7.69%) 
Ferritin - increased  1/13 (7.69%) 
Iron - decreased  1/13 (7.69%) 
Potassium - elevated  3/13 (23.08%) 
Sodium - elevated  1/13 (7.69%) 
Cardiac disorders   
Arrythmia  6/13 (46.15%) 
Cardiac palpitations  1/13 (7.69%) 
Heart Block  1/13 (7.69%) 
Ear and labyrinth disorders   
Hearing Loss  1/13 (7.69%) 
Endocrine disorders   
Hypothyroid  2/13 (15.38%) 
TSH - elevated  1/13 (7.69%) 
Eye disorders   
Vision - hazy  1/13 (7.69%) 
Gastrointestinal disorders   
Cholethisiasis  1/13 (7.69%) 
Diarrhea  1/13 (7.69%) 
GI symptoms  2/13 (15.38%) 
Stool leakage  1/13 (7.69%) 
Vomiting  1/13 (7.69%) 
General disorders   
Impaired balance  2/13 (15.38%) 
Diaphoresis  1/13 (7.69%) 
Dizziness  1/13 (7.69%) 
Dreams (abnormal)  1/13 (7.69%) 
Fatigue  1/13 (7.69%) 
Fever  2/13 (15.38%) 
Glucose - elevated  1/13 (7.69%) 
Hair loss  1/13 (7.69%) 
Malaise  1/13 (7.69%) 
Pain - back  1/13 (7.69%) 
Pain - chest (no specific angina)  3/13 (23.08%) 
Pain - finger  1/13 (7.69%) 
Pain - GI  2/13 (15.38%) 
Pain - knee  2/13 (15.38%) 
Pain - leg (spastic)  1/13 (7.69%) 
Pain - neck area  2/13 (15.38%) 
Pain - pelvic area  1/13 (7.69%) 
Pain - shoulder  1/13 (7.69%) 
PSA - elevated  1/13 (7.69%) 
Throat - dry  1/13 (7.69%) 
Virus - post transplant  1/13 (7.69%) 
Weight loss - unexpected  2/13 (15.38%) 
Immune system disorders   
Allergies  1/13 (7.69%) 
Infections and infestations   
Cold symptoms  5/13 (38.46%) 
Eosinophils - increased  1/13 (7.69%) 
Infection  3/13 (23.08%) 
Sinus Infection  2/13 (15.38%) 
Injury, poisoning and procedural complications   
Injury - trauma  1/13 (7.69%) 
Metabolism and nutrition disorders   
Decreased appetite  1/13 (7.69%) 
Musculoskeletal and connective tissue disorders   
Fracture  3/13 (23.08%) 
Orthopedic  1/13 (7.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer - skin  1/13 (7.69%) 
Nervous system disorders   
Headache  2/13 (15.38%) 
Memory - decreased  1/13 (7.69%) 
Mental status altered  1/13 (7.69%) 
Numbness  1/13 (7.69%) 
Restless Leg Syndrome  1/13 (7.69%) 
Speech - impaired  1/13 (7.69%) 
Stroke - acute ischemic  1/13 (7.69%) 
Tremors  1/13 (7.69%) 
Psychiatric disorders   
Depression  3/13 (23.08%) 
Renal and urinary disorders   
Creatinine worsened  4/13 (30.77%) 
Dialysis  3/13 (23.08%) 
Electrolytes - elevated  1/13 (7.69%) 
Kidney nodules/cysts  1/13 (7.69%) 
Microalbuminuria - worsened  3/13 (23.08%) 
Proteinuria - increased  4/13 (30.77%) 
Prostatic hypertrophy  1/13 (7.69%) 
Prostatitis  1/13 (7.69%) 
Renal failure  3/13 (23.08%) 
Transplant - kidney  1/13 (7.69%) 
Urine - bloody s/p prostate biopsy  1/13 (7.69%) 
Respiratory, thoracic and mediastinal disorders   
Pneumonia  1/13 (7.69%) 
Shortness of Breath  1/13 (7.69%) 
Skin and subcutaneous tissue disorders   
Blisters  2/13 (15.38%) 
Burn  1/13 (7.69%) 
Ecchymosis - varied  1/13 (7.69%) 
Erythema  1/13 (7.69%) 
Itching  1/13 (7.69%) 
Rash  4/13 (30.77%) 
Vascular disorders   
Edema  2/13 (15.38%) 
Hypertension  2/13 (15.38%) 
Hypotension  2/13 (15.38%) 
Small number of subjects. Single group with comparison to baseline data.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Raphael Schiffmann
Organization: Baylor Research Institute
Phone: 214-820-4533
Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00068107     History of Changes
Other Study ID Numbers: 030286
03-N-0286
First Submitted: September 6, 2003
First Posted: September 8, 2003
Results First Submitted: March 12, 2015
Results First Posted: March 31, 2015
Last Update Posted: March 31, 2015