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Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout

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ClinicalTrials.gov Identifier: NCT00325195
Recruitment Status : Completed
First Posted : May 12, 2006
Results First Posted : February 25, 2011
Last Update Posted : February 28, 2011
Sponsor:
Information provided by:
Savient Pharmaceuticals

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Gout
Interventions: Other: placebo
Biological: pegloticase

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Rheumatology practices across the US, Canada and Mexico

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
13 subjects were randomized but withdrew before intervention. These subjects were not part of the modified Intent to Treat Population, which included only subjects who received at least one dose of study drug.

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Participant Flow for 2 periods

Period 1:   Randomized
    q2 Wks   q4 Wks   Placebo
STARTED   90   89   46 
COMPLETED   85   84   43 
NOT COMPLETED   5   5   3 
Not dosed                5                5                3 

Period 2:   Received Intervention: ITT Population
    q2 Wks   q4 Wks   Placebo
STARTED   85   84   43 
COMPLETED   59   59   39 
NOT COMPLETED   26   25   4 
Adverse Event                15                17                1 
Death                3                1                0 
Withdrawal by Subject                7                6                1 
Lost to Follow-up                0                0                2 
Protocol violation/non-compliance                1                1                0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks
Total Total of all reporting groups

Baseline Measures
   q2 Wks   q4 Wks   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 85   84   43   212 
Age 
[Units: Participants]
       
<=18 years   0   0   0   0 
Between 18 and 65 years   56   65   31   152 
>=65 years   29   19   12   60 
Age 
[Units: Years]
Mean (Standard Deviation)
 56.3  (15.53)   54.5  (13.34)   55.4  (12.21)   55.4  (14.01) 
Gender 
[Units: Participants]
       
Female   17   15   7   39 
Male   68   69   36   173 
Region of Enrollment 
[Units: Participants]
       
United States   73   77   39   189 
Canada   1   1   1   3 
Mexico   11   6   3   20 


  Outcome Measures

1.  Primary:   Plasma Uric Acid (PUA) Responder   [ Time Frame: Months 3 and 6 ]

Measure Type Primary
Measure Title Plasma Uric Acid (PUA) Responder
Measure Description PUA Responder was defined as a participant who achieved and maintained plasma uric acid concentrations < 6 mg/dL for at least 80% of the time during months 3 and 6 combined. Participants who withdrew from the study before month 6 were considered non-responders.
Time Frame Months 3 and 6  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Modified ITT (all patients receiving at least one dose of study drug). Participants dropping out before Week 25 were imputed as Non-Responders

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   85   84   43 
Plasma Uric Acid (PUA) Responder 
[Units: Participants]
 36   29   0 


Statistical Analysis 1 for Plasma Uric Acid (PUA) Responder
Groups [1] q2 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Plasma Uric Acid (PUA) Responder
Groups [1] q4 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



2.  Secondary:   Reduction in Tophus Burden   [ Time Frame: Baseline and Final Visit (6 months or LOCF) ]

Measure Type Secondary
Measure Title Reduction in Tophus Burden
Measure Description percentage of tophaceous subjects who demonstrated a complete resolution (100 % decrease in measured area or complete disappearance)of at least one tophus in the absence of other tophus progression or new tophi, as assessed by a blinded Central Reader using standardized digital photographs and image analysis software.
Time Frame Baseline and Final Visit (6 months or LOCF)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed was based upon the number of patients who had one or more tophus at Baseline, as determined by the PI, AND who had at least one follow-up assessment, with the final visit for each subject included (last observation carried forward).

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   52   52   27 
Reduction in Tophus Burden 
[Units: Percent subjects with resolved tophus]
 40   21   7 


Statistical Analysis 1 for Reduction in Tophus Burden
Groups [1] q2 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] <0.002
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Reduction in Tophus Burden
Groups [1] q4 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] 0.200
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Secondary:   Percentage of Subjects With Gout Flare Per 3-month Period   [ Time Frame: Months 1-3 and Months 4-6 ]

Measure Type Secondary
Measure Title Percentage of Subjects With Gout Flare Per 3-month Period
Measure Description Percent of participants reporting a gout flare during Months 1-3 and Months 4-6. Denominator during the respective period was based upon number of participants during that period.
Time Frame Months 1-3 and Months 4-6  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number analyzed in each period was based upon number of participants remaining in study during the assessed treatment period: 85/84/43 in Months 1-3 and 69/69/43 in Months 4-6

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   85   84   43 
Percentage of Subjects With Gout Flare Per 3-month Period 
[Units: Percent subjects reporting flares]
     
Months 1-3   75   81   54 
Months 4-6   41   56   67 


Statistical Analysis 1 for Percentage of Subjects With Gout Flare Per 3-month Period
Groups [1] q2 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] 0.007
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  % of pegloticase q2 participants reporting flares compared to placebo pts during Months 4-6 treatment period
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Percentage of Subjects With Gout Flare Per 3-month Period
Groups [1] q4 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Fisher Exact
P Value [4] 0.321
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  % of pegloticase q4 participants reporting flares compared to placebo pts during Months 4-6 treatment period
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  Secondary:   Change in Number of Swollen Joints   [ Time Frame: Baseline and Final Visit (Month 6 or LOCF) ]

Measure Type Secondary
Measure Title Change in Number of Swollen Joints
Measure Description Change from Baseline to Month 6 (or last observation carried forward)in number of swollen joints per subject. Values were inputed using last observation carried forward analysis for subjects who did not complete the studies.
Time Frame Baseline and Final Visit (Month 6 or LOCF)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All ITT participants with baseline and at least one post-baseline assessment were included in analysis. LOCF was used for participants dropping out early.

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   78   77   43 
Change in Number of Swollen Joints 
[Units: Swollen joints]
Mean (Standard Deviation)
 -5.5  (10.47)   -5.1  (7.83)   -2.6  (11.64) 


Statistical Analysis 1 for Change in Number of Swollen Joints
Groups [1] q2 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] 0.166
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Change in Number of Swollen Joints
Groups [1] q4 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] 0.170
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



5.  Secondary:   Change in Number of Tender Joints   [ Time Frame: Baseline and Final Visit (Month 6 or LOCF) ]

Measure Type Secondary
Measure Title Change in Number of Tender Joints
Measure Description Change from Baseline to Month 6 (or last observation carried forward) in number of tender joints per participant
Time Frame Baseline and Final Visit (Month 6 or LOCF)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All ITT participants with baseline and at least one post-baseline assessment were included in analysis. LOCF was used for participants dropping out early.

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   78   77   43 
Change in Number of Tender Joints 
[Units: Tender joints]
Mean (Standard Deviation)
 -7.4  (11.95)   -6.1  (10.64)   -1.2  (12.30) 


Statistical Analysis 1 for Change in Number of Tender Joints
Groups [1] q2 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] 0.008
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.

Statistical Analysis 2 for Change in Number of Tender Joints
Groups [1] q4 Wks vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] t-test, 2 sided
P Value [4] 0.024
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



6.  Secondary:   Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life   [ Time Frame: Baseline to Final Visit (Month 6 or LOCF) ]

Measure Type Secondary
Measure Title Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life
Measure Description Health Assessment Questionnaire(HAQ: VAS pain scale where 0 (no pain)-100 (severe pain); HAQ disability index (HAQ-DI) on a scale from 0(no disability) to 3 (completely disabled), and a unit change of > or =0.22 is considerd a mimimal clinically important difference(MCID). SF-36 Physical Component Summary Score (SF36-PCS), a composite score where 0 is the worst score and 100 the best possible, and where a change of > or =2.5 units in the PCS is considered a MCID.
Time Frame Baseline to Final Visit (Month 6 or LOCF)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants analyzed was based upon the number who had baseline and at least one follow-up assessment, with the final visit for each subject included (LOCF).

Reporting Groups
  Description
q2 Wks 8 mg pegloticase every 2 weeks
q4 Wks 8 mg pegloticase every 4 weeks (alternating with placebo infusion every 4 weeks)
Placebo placebo infusion every 2 weeks

Measured Values
   q2 Wks   q4 Wks   Placebo 
Participants Analyzed   77   77   43 
Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life 
[Units: Units on a scale]
Mean (Standard Deviation)
     
HAQ-VAS Pain   -11.4  (33.8)   -6.9  (27.0)   1.4  (30.0) 
HAQ-DI   -0.22  (0.64)   -0.20  (0.55)   0.0  (0.41) 
SF-36 PCS   4.4  (9.4)   4.9  (8.5)   -0.3  (9.0) 

No statistical analysis provided for Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director
Organization: Savient Pharmaceuticals, Inc.
phone: 732-418-9300


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Savient Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00325195     History of Changes
Other Study ID Numbers: C0405 & C0406
First Submitted: May 10, 2006
First Posted: May 12, 2006
Results First Submitted: October 13, 2010
Results First Posted: February 25, 2011
Last Update Posted: February 28, 2011