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GoutPhase 3NCT00325195

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

A Phase 3 study testing pegloticase in people with Gout, run by Savient Pharmaceuticals at 56 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gout
What is being tested?
pegloticase
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
225 participants
Where
56 sitesin 3 countries
Study dates
May 2006to Dec 2007
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.)

Who cannot join

  • 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).
Show all 15Show fewer
  • 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.

Trial locations and contacts

56 sites in 3 countries.

56 sites in 3 countries

United States50 sites

  • AAMR Research Clinic

    Amarillo, Texas, 79106

  • Arthritis & Rheumatic Disease Specialties

    Aventura, Florida, 33180

  • Peter A. Holt, M.D.

    Baltimore, Maryland, 21239

  • UAB Arthritis Clinical Intervention Program

    Birmingham, Alabama, 35294

  • Idaho Arthritis & Osteoporosis Center

    Boise, Idaho, 83702

  • Graves Gilbert Clinic

    Bowling Green, Kentucky, 42101

  • Michigan Arthritis Research Center

    Brighton, Michigan, 48116

  • Rheumatology Associates

    Charleston, South Carolina, 29407

  • The University of Chicago

    Chicago, Illinois, 60637

  • New Horizons Clinical Research

    Cincinnati, Ohio, 45242

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Arthritis Associates & Osteoporosis Center of Colorado Springs

    Colorado Springs, Colorado, 80910

  • The Ohio State University

    Columbus, Ohio, 43210

  • STAT Research, Inc.

    Dayton, Ohio, 45402

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Duke University Medical Center

    Durham, North Carolina, 27302

  • Malcom Randall VA Medical Center

    Gainesville, Florida, 32608

  • Rheumatic Disease Center

    Glendale, Wisconsin, 53217

  • Brody School of Medicine, East Carolina University

    Greenville, North Carolina, 27834

  • Physicians East, P.A.

    Greenville, North Carolina, 27834

  • Piedmont Arthritis, PA

    Greenville, South Carolina, 29601

  • Malamet & Klein, MD, PA

    Hagerstown, Maryland, 21740

  • Horizon Institute for Clinical Research

    Hollywood, Florida, 33021

  • Institute of Arthritis Research

    Idaho Falls, Idaho, 83401

  • NEA Clinic

    Jonesboro, Arkansas, 72401

  • UCSD Rheumatology Division

    La Jolla, California, 92037-0943

  • Justus J. Fiechtner, MD, PC

    Lansing, Michigan, 48910

  • David R. Mandel, MD, Inc.

    Mayfield Village, Ohio, 44143

  • Mount Sinai Medical Center

    New York, New York, 10029-6574

  • Ocala Rheumatology Research Center

    Ocala, Florida, 34474

  • Health Research of Oklahoma

    Oklahoma City, Oklahoma, 73139

  • Arthritis & Osteoporosis Treatment Center, PA

    Orange Park, Florida, 32073

  • Mid Atlantic Research Assoc.

    Philadelphia, Pennsylvania, 19154

  • Portland Medical Associates

    Portland, Oregon, 97224

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • CentraCare Clinic

    Saint Cloud, Minnesota, 56377

  • Arthritis & Osteoporosis Center of South Texas

    San Antonio, Texas, 78232

  • Kaiser Permanente Medical Center, Clinical Trials Unit

    San Francisco, California, 94118

  • Pacific Arthritis Center Medical Group

    Santa Maria, California, 93454

  • Arthritis Northwest, PLLC

    Spokane, Washington, 99204

  • St. Petersburg Arthritis Center

    St. Petersburg, Florida, 33703

  • Rheumatology Associates of North Jersey

    Teaneck, New Jersey, 07666

  • University of Arizona Arthritis Center

    Tucson, Arizona, 85724

  • Arthritis & Osteoporosis Clinic Research Center of Central Texas

    Waco, Texas, 76708

  • Veterans Affairs Medical Center

    Washington D.C., District of Columbia, 20422

  • The Center for Rheumatology and Bone Research

    Wheaton, Maryland, 20902

  • E. Robert Harris Medical Corporation

    Whittier, California, 90601

  • Agilence Arthritis & Osteoporosis Medical Center

    Whittier, California, 90606

  • Carolina Atthritis Associates

    Wilmington, North Carolina, 28401

  • Fallon Clinic, Inc

    Worcester, Massachusetts, 01605

Other trials in United States

Mexico4 sites

  • Antiguo Hospital Civil de Guadalajara

    Guadalajara, Jalisco

  • Hospital Civil de Guadalajara

    Guadalajara, Jalisco

  • Clinica para el Diagnostico y Tratamiento de las Enfermedades Rheumaticas

    México, D.f.

  • Hospital General de mexico

    México, D.f.

Other trials in Mexico

Canada2 sites

  • St. Joseph's Health Care

    London, Ontario, N6A 4V2

  • Manitoba Clinic

    Winnipeg, Manitoba, R3A 1M3

Other trials in Canada

About this study

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

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.

Read the 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.

Conditions
Gout
Being tested
placebo, pegloticase
Medical subject headings
Gout

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • placeboOther

    placebo by intravenous infusion every 2 weeks

  • pegloticaseBiological

    Also called PEG-uricase, Puricase

    8 mg pegloticase by intravenous infusion

Study groups in NCT00325195
Study groupRoleWhat they receive
q2 wksExperimental8 mg pegloticase every 2 weeks
Receives: Biological: pegloticase
q4 wksExperimental8 mg pegloticase every 4 weeks (alternating with placebo every 4 weeks)
Receives: Biological: pegloticase
placeboPlacebo comparatorplacebo every 2 weeks
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Months 3 and 6

Secondary outcomes (5)

  1. Reduction in Tophus Burden

    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.

    Measured: Baseline and Final Visit (6 months or LOCF)

  2. Percentage of Subjects With Gout Flare Per 3-month Period

    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.

    Measured: Months 1-3 and Months 4-6

  3. Change in Number of Swollen Joints

    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.

    Measured: Baseline and Final Visit (Month 6 or LOCF)

  4. Change in Number of Tender Joints

    Change from Baseline to Month 6 (or last observation carried forward) in number of tender joints per participant

    Measured: Baseline and Final Visit (Month 6 or LOCF)

  5. Change in Patient Reported Outcomes of Pain, Physical Function and Quality of Life

    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.

    Measured: Baseline to Final Visit (Month 6 or LOCF)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionOct 2007
  4. Study completionDec 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
225 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00325195
Sponsor's protocol ID
C0405 & C0406
Status last verified
Feb 2011
First submitted
10 May 2006
Last updated
28 Feb 2011
Data monitoring committee
No

Publications

  • 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.

    PubMed 31203212

  • 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.

    PubMed 31079535

  • 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.

    PubMed 24588936

  • 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.

    PubMed 24447425

  • 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.

    PubMed 24286509

  • 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.

    PubMed 21846852

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pegloticase in people with Gout, run by Savient Pharmaceuticals at 56 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Mexico, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Uric Acid (PUA) Responder (time frame: Months 3 and 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00325195, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2011.

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