Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout
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
1 other identifier
interventional
225
3 countries
56
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started May 2006
56 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2006
CompletedFirst Submitted
Initial submission to the registry
May 10, 2006
CompletedFirst Posted
Study publicly available on registry
May 12, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2007
CompletedResults Posted
Study results publicly available
February 25, 2011
CompletedFebruary 28, 2011
February 1, 2011
1.4 years
May 10, 2006
October 13, 2010
February 24, 2011
Conditions
Outcome Measures
Primary Outcomes (1)
Plasma Uric Acid (PUA) Responder
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.
Months 3 and 6
Secondary Outcomes (5)
Reduction in Tophus Burden
Baseline and Final Visit (6 months or LOCF)
Percentage of Subjects With Gout Flare Per 3-month Period
Months 1-3 and Months 4-6
Change in Number of Swollen Joints
Baseline and Final Visit (Month 6 or LOCF)
Change in Number of Tender Joints
Baseline and Final Visit (Month 6 or LOCF)
Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life
Baseline to Final Visit (Month 6 or LOCF)
Study Arms (3)
q2 wks
EXPERIMENTAL8 mg pegloticase every 2 weeks
q4 wks
EXPERIMENTAL8 mg pegloticase every 4 weeks (alternating with placebo every 4 weeks)
placebo
PLACEBO COMPARATORplacebo every 2 weeks
Interventions
8 mg pegloticase by intravenous infusion
Eligibility Criteria
You may qualify if:
- Outpatients of either gender, age 18 or older ( no upper age limit).
- Patient is hyperuricemic: screening serum uric acid must be ≥8 mg/dL.
- 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).
- 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.
- 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).
- 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.)
You may not qualify if:
- The patient has unstable angina.
- The patient has uncontrolled arrhythmia.
- The patient has non-compensated congestive heart failure.
- The patient has uncontrolled hypertension (above 150/95).
- The patient has a history of end stage renal disease requiring dialysis.
- The patient has hemoglobin \< 8 g/dL (males) or \< 7 g/dL (females).
- The patient is an organ transplant recipient
- The patient has had prior treatment with PEG-uricase, or other recombinant uricase, or any concomitant therapy with a PEG-conjugated drug.
- 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).
- The patient has glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- The patient has a history of anaphylactic reaction to a recombinant protein or porcine product, or hypersensitivity to PEG.
- The patient is pregnant or breast feeding.
- 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.
- The patient has a known allergy to urate oxidase or PEGylated products.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (56)
UAB Arthritis Clinical Intervention Program
Birmingham, Alabama, 35294, United States
University of Arizona Arthritis Center
Tucson, Arizona, 85724, United States
NEA Clinic
Jonesboro, Arkansas, 72401, United States
UCSD Rheumatology Division
La Jolla, California, 92037-0943, United States
Kaiser Permanente Medical Center, Clinical Trials Unit
San Francisco, California, 94118, United States
Pacific Arthritis Center Medical Group
Santa Maria, California, 93454, United States
E. Robert Harris Medical Corporation
Whittier, California, 90601, United States
Agilence Arthritis & Osteoporosis Medical Center
Whittier, California, 90606, United States
Arthritis Associates & Osteoporosis Center of Colorado Springs
Colorado Springs, Colorado, 80910, United States
Veterans Affairs Medical Center
Washington D.C., District of Columbia, 20422, United States
Arthritis & Rheumatic Disease Specialties
Aventura, Florida, 33180, United States
Malcom Randall VA Medical Center
Gainesville, Florida, 32608, United States
Horizon Institute for Clinical Research
Hollywood, Florida, 33021, United States
Ocala Rheumatology Research Center
Ocala, Florida, 34474, United States
Arthritis & Osteoporosis Treatment Center, PA
Orange Park, Florida, 32073, United States
St. Petersburg Arthritis Center
St. Petersburg, Florida, 33703, United States
Idaho Arthritis & Osteoporosis Center
Boise, Idaho, 83702, United States
Institute of Arthritis Research
Idaho Falls, Idaho, 83401, United States
The University of Chicago
Chicago, Illinois, 60637, United States
Graves Gilbert Clinic
Bowling Green, Kentucky, 42101, United States
Peter A. Holt, M.D.
Baltimore, Maryland, 21239, United States
Malamet & Klein, MD, PA
Hagerstown, Maryland, 21740, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902, United States
Fallon Clinic, Inc
Worcester, Massachusetts, 01605, United States
Michigan Arthritis Research Center
Brighton, Michigan, 48116, United States
Justus J. Fiechtner, MD, PC
Lansing, Michigan, 48910, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
CentraCare Clinic
Saint Cloud, Minnesota, 56377, United States
Rheumatology Associates of North Jersey
Teaneck, New Jersey, 07666, United States
Mount Sinai Medical Center
New York, New York, 10029-6574, United States
Duke University Medical Center
Durham, North Carolina, 27302, United States
Brody School of Medicine, East Carolina University
Greenville, North Carolina, 27834, United States
Physicians East, P.A.
Greenville, North Carolina, 27834, United States
Carolina Atthritis Associates
Wilmington, North Carolina, 28401, United States
New Horizons Clinical Research
Cincinnati, Ohio, 45242, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
The Ohio State University
Columbus, Ohio, 43210, United States
STAT Research, Inc.
Dayton, Ohio, 45402, United States
David R. Mandel, MD, Inc.
Mayfield Village, Ohio, 44143, United States
Health Research of Oklahoma
Oklahoma City, Oklahoma, 73139, United States
Portland Medical Associates
Portland, Oregon, 97224, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
Mid Atlantic Research Assoc.
Philadelphia, Pennsylvania, 19154, United States
Rheumatology Associates
Charleston, South Carolina, 29407, United States
Piedmont Arthritis, PA
Greenville, South Carolina, 29601, United States
AAMR Research Clinic
Amarillo, Texas, 79106, United States
Arthritis & Osteoporosis Center of South Texas
San Antonio, Texas, 78232, United States
Arthritis & Osteoporosis Clinic Research Center of Central Texas
Waco, Texas, 76708, United States
Arthritis Northwest, PLLC
Spokane, Washington, 99204, United States
Rheumatic Disease Center
Glendale, Wisconsin, 53217, United States
Manitoba Clinic
Winnipeg, Manitoba, R3A 1M3, Canada
St. Joseph's Health Care
London, Ontario, N6A 4V2, Canada
Clinica para el Diagnostico y Tratamiento de las Enfermedades Rheumaticas
México, D.f., Mexico
Hospital General de mexico
México, D.f., Mexico
Antiguo Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico
Hospital Civil de Guadalajara
Guadalajara, Jalisco, Mexico
Related Publications (6)
Pillinger MH, Fields TR, Yeo AE, Lipsky PE. Dissociation Between Clinical Benefit and Persistent Urate Lowering in Patients with Chronic Refractory Gout Treated with Pegloticase. J Rheumatol. 2020 Apr;47(4):605-612. doi: 10.3899/jrheum.190161. Epub 2019 Jun 15.
PMID: 31203212DERIVEDJohnson RJ, Choi HK, Yeo AE, Lipsky PE. Pegloticase Treatment Significantly Decreases Blood Pressure in Patients With Chronic Gout. Hypertension. 2019 Jul;74(1):95-101. doi: 10.1161/HYPERTENSIONAHA.119.12727. Epub 2019 May 13.
PMID: 31079535DERIVEDLipsky PE, Calabrese LH, Kavanaugh A, Sundy JS, Wright D, Wolfson M, Becker MA. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res Ther. 2014 Mar 4;16(2):R60. doi: 10.1186/ar4497.
PMID: 24588936DERIVEDYood RA, Ottery FD, Irish W, Wolfson M. Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials. BMC Res Notes. 2014 Jan 21;7:54. doi: 10.1186/1756-0500-7-54.
PMID: 24447425DERIVEDBaraf HS, Becker MA, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, Rehrig CD, Ottery FD, Sundy JS, Yood RA. Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy. Arthritis Res Ther. 2013 Sep 26;15(5):R137. doi: 10.1186/ar4318.
PMID: 24286509DERIVEDSundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vazquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW 2nd, Hamburger SA, Becker MA. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011 Aug 17;306(7):711-20. doi: 10.1001/jama.2011.1169.
PMID: 21846852DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Savient Pharmaceuticals, Inc.
Study Officials
- STUDY DIRECTOR
Medical Director, MD
Savient Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
May 10, 2006
First Posted
May 12, 2006
Study Start
May 1, 2006
Primary Completion
October 1, 2007
Study Completion
December 1, 2007
Last Updated
February 28, 2011
Results First Posted
February 25, 2011
Record last verified: 2011-02