Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout
These are two replicate studies to evaluate the safety and efficacy of PEG (polyethylene glycol)-uricase in controlling the uric acid level in symptomatic gout patients with high uric acid levels who are unable to take standard gout therapies, or for whom those therapies have been unsuccessful in controlling their uric acid level.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomized, Multicenter, Double-blind, Placebo-controlled Efficacy and Safety Study of 8 mg PEG-uricase in Two Dose Regimens in Hyperuricemic Subjects With Symptomatic Gout|
- Plasma Uric Acid (PUA) Responder [ Time Frame: Months 3 and 6 ] [ Designated as safety issue: No ]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.
- Reduction in Tophus Burden [ Time Frame: Baseline and Final Visit (6 months or LOCF) ] [ Designated as safety issue: No ]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.
- Percentage of Subjects With Gout Flare Per 3-month Period [ Time Frame: Months 1-3 and Months 4-6 ] [ Designated as safety issue: No ]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.
- Change in Number of Swollen Joints [ Time Frame: Baseline and Final Visit (Month 6 or LOCF) ] [ Designated as safety issue: No ]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.
- Change in Number of Tender Joints [ Time Frame: Baseline and Final Visit (Month 6 or LOCF) ] [ Designated as safety issue: No ]Change from Baseline to Month 6 (or last observation carried forward) in number of tender joints per participant
- Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life [ Time Frame: Baseline to Final Visit (Month 6 or LOCF) ] [ Designated as safety issue: No ]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.
|Study Start Date:||May 2006|
|Study Completion Date:||December 2007|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
Experimental: q2 wks
8 mg pegloticase every 2 weeks
8 mg pegloticase by intravenous infusion
Experimental: q4 wks
8 mg pegloticase every 4 weeks (alternating with placebo every 4 weeks)
8 mg pegloticase by intravenous infusion
Placebo Comparator: placebo
placebo every 2 weeks
placebo by intravenous infusion every 2 weeks
The primary objective of each of the studies is to demonstrate superiority in the response rate (control of uric acid levels to below 6 mg/dL) in the PEG-uricase treatment groups compared to the placebo-control group.
While reduction or resolution of tophi have been reported in the setting of prolonged urate-lowering therapy, there is photographic and additional anecdotal evidence from the Phase 2 PEG-uricase study of resolution or significant reduction of tophi after 3 months of therapy. Therefore, an assessment of changes in tophi over time will be conducted through the use of digital photographs obtained in a standardized manner from all subjects during the study. The effect on other clinical outcomes, including quality of life, health-related disability measures, gout flares and the number of swollen and tender joints will also be compared between the treatment groups and control group. Subjects will be randomized to one of the three treatment arms in a 2:2:1 ratio: 8 mg PEG-uricase every 2 weeks; 8 mg PEG-uricase every 4 weeks; or placebo. All subjects will receive an intravenous infusion (PEG-uricase or placebo) every two weeks in order to maintain the blind throughout the study. Study duration is approximately 26 weeks, including two weeks for screening and 24 weeks (6 months) of treatment.
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|Study Director:||Medical Director, MD||Savient Pharmaceuticals, Inc.|