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

This study has been completed.
Sponsor:
Information provided by:
Savient Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00325195
First received: May 10, 2006
Last updated: February 24, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Gout
Other: placebo
Biological: pegloticase
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Savient Pharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 225
Study Start Date: May 2006
Study Completion Date: December 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: q2 wks
8 mg pegloticase every 2 weeks
Biological: pegloticase
8 mg pegloticase by intravenous infusion
Other Names:
  • PEG-uricase
  • Puricase
Experimental: q4 wks
8 mg pegloticase every 4 weeks (alternating with placebo every 4 weeks)
Biological: pegloticase
8 mg pegloticase by intravenous infusion
Other Names:
  • PEG-uricase
  • Puricase
Placebo Comparator: placebo
placebo every 2 weeks
Other: placebo
placebo by intravenous infusion every 2 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Outpatients of either gender, age 18 or older ( no upper age limit).
  2. Patient is hyperuricemic: screening serum uric acid must be ≥8 mg/dL.
  3. Patient has symptomatic gout (presence of at least 3 gout flares in the 18 months prior to entry, or at least one gout tophus, or gouty arthritis).
  4. Conventional therapy is contraindicated or has been ineffective in this patient, i.e., patient has a history (either by medical record or patient interview) of hypersensitivity or of failure to normalize SUA with at least 3 months treatment with allopurinol at the maximum labeled dose (800 mg/dL in the U.S.), or at a medically appropriate lower dose based on dose-limiting toxicity or dose-limiting co-morbidity.
  5. Patient is willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed, including washout).
  6. If the patient is a woman of childbearing potential, she must have had a negative screening serum pregnancy test and must use a medically approved form of birth control during her participation in the protocol. Such methods include oral, injectable or implantable contraceptives; IUDs and barrier contraceptives in combination with spermicide. (If male or surgically sterile, check N/A.)

Exclusion Criteria:

  1. The patient has unstable angina.
  2. The patient has uncontrolled arrhythmia.
  3. The patient has non-compensated congestive heart failure.
  4. The patient has uncontrolled hypertension (above 150/95).
  5. The patient has a history of end stage renal disease requiring dialysis.
  6. The patient has hemoglobin < 8 g/dL (males) or < 7 g/dL (females).
  7. The patient is an organ transplant recipient
  8. The patient has had prior treatment with PEG-uricase, or other recombinant uricase, or any concomitant therapy with a PEG-conjugated drug.
  9. The patient has had a gout flare at screening that is resolved for less than one week prior to first treatment with study drug (exclusive of chronic synovitis/ arthritis).
  10. The patient has glucose-6-phosphate dehydrogenase (G6PD) deficiency.
  11. The patient has a history of anaphylactic reaction to a recombinant protein or porcine product, or hypersensitivity to PEG.
  12. The patient is pregnant or breast feeding.
  13. The patient has taken an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study.
  14. The patient has a known allergy to urate oxidase or PEGylated products.
  15. The patient has any other medical or psychological condition which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00325195

  Show 56 Study Locations
Sponsors and Collaborators
Savient Pharmaceuticals
Investigators
Study Director: Medical Director, MD Savient Pharmaceuticals, Inc.
  More Information

Additional Information:
No publications provided by Savient Pharmaceuticals

Additional 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
Study First Received: May 10, 2006
Results First Received: October 13, 2010
Last Updated: February 24, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gout
Hyperuricemia
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 30, 2014