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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:

Study Description
Brief Summary:
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 or disease Intervention/treatment Phase
Gout Other: placebo Biological: pegloticase Phase 3

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : May 2006
Primary Completion Date : October 2007
Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Gout
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. Plasma Uric Acid (PUA) Responder [ Time Frame: Months 3 and 6 ]
    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 :
  1. Reduction in Tophus Burden [ Time Frame: Baseline and Final Visit (6 months or LOCF) ]
    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.

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

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

  4. Change in Number of Tender Joints [ Time Frame: Baseline and Final Visit (Month 6 or LOCF) ]
    Change from Baseline to Month 6 (or last observation carried forward) in number of tender joints per participant

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


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00325195


  Hide Study Locations
Locations
United States, Alabama
UAB Arthritis Clinical Intervention Program
Birmingham, Alabama, United States, 35294
United States, Arizona
University of Arizona Arthritis Center
Tucson, Arizona, United States, 85724
United States, Arkansas
NEA Clinic
Jonesboro, Arkansas, United States, 72401
United States, California
UCSD Rheumatology Division
La Jolla, California, United States, 92037-0943
Kaiser Permanente Medical Center, Clinical Trials Unit
San Francisco, California, United States, 94118
Pacific Arthritis Center Medical Group
Santa Maria, California, United States, 93454
E. Robert Harris Medical Corporation
Whittier, California, United States, 90601
Agilence Arthritis & Osteoporosis Medical Center
Whittier, California, United States, 90606
United States, Colorado
Arthritis Associates & Osteoporosis Center of Colorado Springs
Colorado Springs, Colorado, United States, 80910
United States, District of Columbia
Veterans Affairs Medical Center
Washington, District of Columbia, United States, 20422
United States, Florida
Arthritis & Rheumatic Disease Specialties
Aventura, Florida, United States, 33180
Malcom Randall VA Medical Center
Gainesville, Florida, United States, 32608
Horizon Institute for Clinical Research
Hollywood, Florida, United States, 33021
Ocala Rheumatology Research Center
Ocala, Florida, United States, 34474
Arthritis & Osteoporosis Treatment Center, PA
Orange Park, Florida, United States, 32073
St. Petersburg Arthritis Center
St. Petersburg, Florida, United States, 33703
United States, Idaho
Idaho Arthritis & Osteoporosis Center
Boise, Idaho, United States, 83702
Institute of Arthritis Research
Idaho Falls, Idaho, United States, 83401
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Graves Gilbert Clinic
Bowling Green, Kentucky, United States, 42101
United States, Maryland
Peter A. Holt, M.D.
Baltimore, Maryland, United States, 21239
Malamet & Klein, MD, PA
Hagerstown, Maryland, United States, 21740
The Center for Rheumatology and Bone Research
Wheaton, Maryland, United States, 20902
United States, Massachusetts
Fallon Clinic, Inc
Worcester, Massachusetts, United States, 01605
United States, Michigan
Michigan Arthritis Research Center
Brighton, Michigan, United States, 48116
Justus J. Fiechtner, MD, PC
Lansing, Michigan, United States, 48910
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
CentraCare Clinic
St. Cloud, Minnesota, United States, 56377
United States, New Jersey
Rheumatology Associates of North Jersey
Teaneck, New Jersey, United States, 07666
United States, New York
Mount Sinai Medical Center
New York, New York, United States, 10029-6574
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27302
Brody School of Medicine, East Carolina University
Greenville, North Carolina, United States, 27834
Physicians East, P.A.
Greenville, North Carolina, United States, 27834
Carolina Atthritis Associates
Wilmington, North Carolina, United States, 28401
United States, Ohio
New Horizons Clinical Research
Cincinnati, Ohio, United States, 45242
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
The Ohio State University
Columbus, Ohio, United States, 43210
STAT Research, Inc.
Dayton, Ohio, United States, 45402
David R. Mandel, MD, Inc.
Mayfield Village, Ohio, United States, 44143
United States, Oklahoma
Health Research of Oklahoma
Oklahoma City, Oklahoma, United States, 73139
United States, Oregon
Portland Medical Associates
Portland, Oregon, United States, 97224
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
Mid Atlantic Research Assoc.
Philadelphia, Pennsylvania, United States, 19154
United States, South Carolina
Rheumatology Associates
Charleston, South Carolina, United States, 29407
Piedmont Arthritis, PA
Greenville, South Carolina, United States, 29601
United States, Texas
AAMR Research Clinic
Amarillo, Texas, United States, 79106
Arthritis & Osteoporosis Center of South Texas
San Antonio, Texas, United States, 78232
Arthritis & Osteoporosis Clinic Research Center of Central Texas
Waco, Texas, United States, 76708
United States, Washington
Arthritis Northwest, PLLC
Spokane, Washington, United States, 99204
United States, Wisconsin
Rheumatic Disease Center
Glendale, Wisconsin, United States, 53217
Canada, Manitoba
Manitoba Clinic
Winnipeg, Manitoba, Canada, R3A 1M3
Canada, Ontario
St. Joseph's Health Care
London, Ontario, Canada, N6A 4V2
Mexico
Clinica para el Diagnostico y Tratamiento de las Enfermedades Rheumaticas
Mexico, D.f., Mexico
Hospital General de mexico
Mexico, D.f., Mexico
Antiguo Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico
Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico
Sponsors and Collaborators
Savient Pharmaceuticals
Investigators
Study Director: Medical Director, MD Savient Pharmaceuticals, Inc.
More Information

Additional Information:
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 Posted: May 12, 2006    Key Record Dates
Results First Posted: February 25, 2011
Last Update Posted: February 28, 2011
Last Verified: February 2011

Additional relevant MeSH terms:
Gout
Hyperuricemia
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes
Rasburicase
Gout Suppressants
Antirheumatic Agents