Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout
NCT ID: NCT00325195
Last Updated: 2011-02-28
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
225 participants
INTERVENTIONAL
2006-05-31
2007-12-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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q2 wks
8 mg pegloticase every 2 weeks
pegloticase
8 mg pegloticase by intravenous infusion
q4 wks
8 mg pegloticase every 4 weeks (alternating with placebo every 4 weeks)
pegloticase
8 mg pegloticase by intravenous infusion
placebo
placebo every 2 weeks
placebo
placebo by intravenous infusion every 2 weeks
Interventions
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placebo
placebo by intravenous infusion every 2 weeks
pegloticase
8 mg pegloticase by intravenous infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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Savient Pharmaceuticals
INDUSTRY
Responsible Party
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Savient Pharmaceuticals, Inc
Principal Investigators
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Medical Director, MD
Role: STUDY_DIRECTOR
Savient Pharmaceuticals, Inc.
Locations
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UAB Arthritis Clinical Intervention Program
Birmingham, Alabama, United States
University of Arizona Arthritis Center
Tucson, Arizona, United States
NEA Clinic
Jonesboro, Arkansas, United States
UCSD Rheumatology Division
La Jolla, California, United States
Kaiser Permanente Medical Center, Clinical Trials Unit
San Francisco, California, United States
Pacific Arthritis Center Medical Group
Santa Maria, California, United States
E. Robert Harris Medical Corporation
Whittier, California, United States
Agilence Arthritis & Osteoporosis Medical Center
Whittier, California, United States
Arthritis Associates & Osteoporosis Center of Colorado Springs
Colorado Springs, Colorado, United States
Veterans Affairs Medical Center
Washington D.C., District of Columbia, United States
Arthritis & Rheumatic Disease Specialties
Aventura, Florida, United States
Malcom Randall VA Medical Center
Gainesville, Florida, United States
Horizon Institute for Clinical Research
Hollywood, Florida, United States
Ocala Rheumatology Research Center
Ocala, Florida, United States
Arthritis & Osteoporosis Treatment Center, PA
Orange Park, Florida, United States
St. Petersburg Arthritis Center
St. Petersburg, Florida, United States
Idaho Arthritis & Osteoporosis Center
Boise, Idaho, United States
Institute of Arthritis Research
Idaho Falls, Idaho, United States
The University of Chicago
Chicago, Illinois, United States
Graves Gilbert Clinic
Bowling Green, Kentucky, United States
Peter A. Holt, M.D.
Baltimore, Maryland, United States
Malamet & Klein, MD, PA
Hagerstown, Maryland, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, United States
Fallon Clinic, Inc
Worcester, Massachusetts, United States
Michigan Arthritis Research Center
Brighton, Michigan, United States
Justus J. Fiechtner, MD, PC
Lansing, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
CentraCare Clinic
Saint Cloud, Minnesota, United States
Rheumatology Associates of North Jersey
Teaneck, New Jersey, United States
Mount Sinai Medical Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Brody School of Medicine, East Carolina University
Greenville, North Carolina, United States
Physicians East, P.A.
Greenville, North Carolina, United States
Carolina Atthritis Associates
Wilmington, North Carolina, United States
New Horizons Clinical Research
Cincinnati, Ohio, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, United States
The Ohio State University
Columbus, Ohio, United States
STAT Research, Inc.
Dayton, Ohio, United States
David R. Mandel, MD, Inc.
Mayfield Village, Ohio, United States
Health Research of Oklahoma
Oklahoma City, Oklahoma, United States
Portland Medical Associates
Portland, Oregon, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States
Mid Atlantic Research Assoc.
Philadelphia, Pennsylvania, United States
Rheumatology Associates
Charleston, South Carolina, United States
Piedmont Arthritis, PA
Greenville, South Carolina, United States
AAMR Research Clinic
Amarillo, Texas, United States
Arthritis & Osteoporosis Center of South Texas
San Antonio, Texas, United States
Arthritis & Osteoporosis Clinic Research Center of Central Texas
Waco, Texas, United States
Arthritis Northwest, PLLC
Spokane, Washington, United States
Rheumatic Disease Center
Glendale, Wisconsin, United States
Manitoba Clinic
Winnipeg, Manitoba, Canada
St. Joseph's Health Care
London, Ontario, 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
Countries
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References
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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.
Johnson 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.
Lipsky 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.
Yood 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.
Baraf 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.
Sundy 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.
Other Identifiers
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C0405 & C0406
Identifier Type: -
Identifier Source: org_study_id