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Pegylated Recombinant Mammalian Uricase (PEG-uricase) as Treatment for Refractory Gout

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ClinicalTrials.gov Identifier: NCT00111657
Recruitment Status : Completed
First Posted : May 25, 2005
Results First Posted : January 18, 2013
Last Update Posted : October 3, 2014
Sponsor:
Collaborator:
Savient Pharmaceuticals
Information provided by (Responsible Party):
John Sundy, Duke University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gout
Intervention Biological: Pegloticase
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Single Arm - Pegloticase
Hide Arm/Group Description [Not Specified]
Period Title: Overall Study
Started 37 [1]
Completed 21 [2]
Not Completed 16
[1]
37 consented. 30 initiated treatment. 29 completed at least 1 dose.
[2]
Completed all intended doses.
Arm/Group Title Single Arm - Pegloticase
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
<=18 years
0
   0.0%
Between 18 and 65 years
25
  67.6%
>=65 years
12
  32.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants
57.6  (14.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
9
  24.3%
Male
28
  75.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 37 participants
37
Baseline urate concentration (pUA)  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 37 participants
10.8  (1.2)
1.Primary Outcome
Title Reduction in Plasma Uric Acid to Less Than 6 mg/dL.
Hide Description [Not Specified]
Time Frame Baseline to Day 105
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: Participants
17
2.Secondary Outcome
Title Clinical Response: Number of Swollen and Tender Joints
Hide Description Count of tenderness and swelling of 68 joints
Time Frame Basline and day 134
Hide Outcome Measure Data
Hide Analysis Population Description
30 subject assesed at baseline. 21 subjects who completed study were assesed at day 134
Arm/Group Title Pegloticase
Hide Arm/Group Description:

All study participants received intravenous pegloticase at dose of 8 mg, administered every 21 days for a maximum of 5 doses.

There was no control group for this open label study.

Pegloticase: 8 mg of Pegloticase administered IV every 3 weeks; total number of infusions is 5

Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: joints
Number of Tender joints at baseline
13
(6 to 21)
Number of Tender joints at day 134
2
(1 to 9)
Number of Swollen jonts at baseline
9
(5 to 20)
Number of Swollen jonts at day 134
6
(2 to 11)
3.Secondary Outcome
Title In a Subset of Subjects Who Volunteer Separately, Change in Uric Acid Pool Size Will be Assessed by a Method That Involves Infusion of Uric Acid Labeled With N15, a Stable (Nonradioactive) Isotope of Nitrogen.
Hide Description [Not Specified]
Time Frame baseline and 7 weeks after last infusion
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Reduction of the Ratio of Uric Acid:Creatinine in Urine
Hide Description [Not Specified]
Time Frame baseline then weekly
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Development of Antibodies to PEG-uricase
Hide Description Number of patients who developed antibodies to PEG-uricase
Time Frame baseline, then prior to infusions and 7 wks after last infusion
Hide Outcome Measure Data
Hide Analysis Population Description
One subject withdrew prior to completing the first infusion and is not included in this analysis.
Arm/Group Title Pegloticase
Hide Arm/Group Description:

All study participants received intravenous pegloticase at dose of 8 mg, administered every 21 days for a maximum of 5 doses.

There was no control group for this open label study.

Pegloticase: 8 mg of Pegloticase administered IV every 3 weeks; total number of infusions is 5

Overall Number of Participants Analyzed 29
Measure Type: Number
Unit of Measure: participants
15
6.Secondary Outcome
Title Infusion 1: Maximum Concentration (Cmax) Value
Hide Description The highest drug concentration in the blood after the first infusion of study drug.
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
One subject withdrew prior to completing the first infusion and is not included in this analysis.
Arm/Group Title Single Arm - Pegloticase
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 29
Mean (Standard Deviation)
Unit of Measure: mU/mL
25.6  (5.0)
7.Secondary Outcome
Title Infusion 1: Minimum Concentration (Cmin)
Hide Description The lowest drug concentration in the blood after the first infusion of study drug.
Time Frame 21 days after the infusion
Hide Outcome Measure Data
Hide Analysis Population Description
One subject withdrew prior to completing the first infusion and is not included in this analysis.
Arm/Group Title Single Arm - Pegloticase
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 29
Mean (Standard Deviation)
Unit of Measure: mU/mL
4.9  (4.6)
Time Frame Day 134
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Single Arm - Pegloticase
Hide Arm/Group Description [Not Specified]
All-Cause Mortality
Single Arm - Pegloticase
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Single Arm - Pegloticase
Affected / at Risk (%) # Events
Total   4/30 (13.33%)    
Cardiac disorders   
Death * 1  1/30 (3.33%)  1
Endocrine disorders   
Hyperglycemia * 1  1/30 (3.33%)  1
Gastrointestinal disorders   
Gastrointestinal bleeding. * 1  1/30 (3.33%)  1
Bowel perforation. * 1  1/30 (3.33%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, Physician defined.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Single Arm - Pegloticase
Affected / at Risk (%) # Events
Total   30/30 (100.00%)    
Blood and lymphatic system disorders   
Anemia * 1  1/30 (3.33%)  1
Cardiac disorders   
Hypertension * 1  4/30 (13.33%)  4
Hypotension * 1  2/30 (6.67%)  2
Edema * 1  3/30 (10.00%)  3
Syncope * 1  1/30 (3.33%)  1
Endocrine disorders   
Hyperkalemia * 1  1/30 (3.33%)  1
Hyperglycemia * 1  1/30 (3.33%)  1
Eye disorders   
Blurred vision * 1  1/30 (3.33%)  1
Conjunctival injection * 1  1/30 (3.33%)  1
Gastrointestinal disorders   
Abdominal cramping * 1  1/30 (3.33%)  1
Diarrhea * 1  3/30 (10.00%)  4
Duodenal ulcer * 1  1/30 (3.33%)  1
Heartburn * 1  3/30 (10.00%)  4
Nausea * 1  5/30 (16.67%)  6
Indigestion * 1  1/30 (3.33%)  1
Toothache * 1  1/30 (3.33%)  1
General disorders   
Chills * 1  2/30 (6.67%)  3
Fever * 1  2/30 (6.67%)  3
Lightheadedness * 1  1/30 (3.33%)  2
Infections and infestations   
Gastroenteritis * 1  3/30 (10.00%)  3
Infected tophus * 1  1/30 (3.33%)  1
Rectal abscess * 1  1/30 (3.33%)  1
Skin abscess * 1  1/30 (3.33%)  1
Thrush * 1  1/30 (3.33%)  1
Upper respiratory infection * 1  2/30 (6.67%)  2
Tooth abscess * 1  2/30 (6.67%)  2
Urinary tract infection * 1  1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  2/30 (6.67%)  2
Back pain * 1  3/30 (10.00%)  3
Bursitis * 1  1/30 (3.33%)  1
Charcot joint * 1  1/30 (3.33%)  1
Draining tophus * 1  2/30 (6.67%)  2
Gout flare * 1  27/30 (90.00%)  119
Joint stiffness * 1  1/30 (3.33%)  1
Pain in limb * 1  2/30 (6.67%)  3
Chronic gouty arthritis * 1  5/30 (16.67%)  5
Nervous system disorders   
Headache * 1  3/30 (10.00%)  3
Parasthesia * 1  2/30 (6.67%)  2
Tremor * 1  1/30 (3.33%)  1
Psychiatric disorders   
Confusion * 1  1/30 (3.33%)  1
Decreased libido * 1  1/30 (3.33%)  1
Excessive sleepiness * 1  1/30 (3.33%)  1
Hallucinations * 1  1/30 (3.33%)  1
Insomnia * 1  1/30 (3.33%)  1
Labile affect * 1  2/30 (6.67%)  2
Renal and urinary disorders   
Urinary hesitancy * 1  1/30 (3.33%)  2
Respiratory, thoracic and mediastinal disorders   
Chest pain * 1  1/30 (3.33%)  1
Chest tightness * 1  2/30 (6.67%)  2
Dyspnea * 1  1/30 (3.33%)  1
Obstructive sleep apnea * 1  1/30 (3.33%)  1
Hypoxemia * 1  2/30 (6.67%)  2
Shortness of breath * 1  1/30 (3.33%)  1
Skin and subcutaneous tissue disorders   
Acne * 1  1/30 (3.33%)  1
Contact dermatitis * 1  2/30 (6.67%)  2
Rash * 1  4/30 (13.33%)  5
Foot ulcer * 1  2/30 (6.67%)  2
Hair loss * 1  1/30 (3.33%)  1
Leg ulcer * 1  2/30 (6.67%)  2
Petechiae * 1  1/30 (3.33%)  1
Pruritis * 1  2/30 (6.67%)  7
Swellng of toes * 1  1/30 (3.33%)  1
Urticaria * 1  2/30 (6.67%)  3
Nevi * 1  1/30 (3.33%)  1
Seborrheic keratosis * 1  1/30 (3.33%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, Physician defined.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John S. Sundy, MD, PhD
Organization: Duke University Medical Center
Phone: 919-684-2347
EMail: john.sundy@duke.edu
Layout table for additonal information
Responsible Party: John Sundy, Duke University
ClinicalTrials.gov Identifier: NCT00111657     History of Changes
Other Study ID Numbers: Pro00006845
FD-R-0002537 ( Other Identifier: FDA OOPD )
First Submitted: May 24, 2005
First Posted: May 25, 2005
Results First Submitted: December 12, 2012
Results First Posted: January 18, 2013
Last Update Posted: October 3, 2014