Pegylated Recombinant Mammalian Uricase (PEG-uricase) as Treatment for Refractory Gout

NCT00111657 | Completed Phase 2 Results

• 2 other identifiers: Pro00006845FD-R-0002537
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether PEG-uricase (a chemically modified recombinant mammalian enzyme that degrades uric acid) is effective in controlling hyperuricemia in patients with chronic gout, who cannot tolerate, or have not responded adequately, to conventional therapy for gout. Funding Source - FDA OOPD

Conditions

Gout

Keywords

Gout; Tophi; Tophaceous gout; Allergy to allopurinol; Post-transplant gout

Outcome Measures

Primary Outcomes (1)

• Reduction in Plasma Uric Acid to Less Than 6 mg/dL.

  Baseline to Day 105

Secondary Outcomes (6)

• Clinical Response: Number of Swollen and Tender Joints

  Basline and day 134

• In a Subset of Subjects Who Volunteer Separately, Change in Uric Acid Pool Size Will be Assessed by a Method That Involves Infusion of Uric Acid Labeled With N15, a Stable (Nonradioactive) Isotope of Nitrogen.

  baseline and 7 weeks after last infusion

• Reduction of the Ratio of Uric Acid:Creatinine in Urine

  baseline then weekly

• Development of Antibodies to PEG-uricase

  baseline, then prior to infusions and 7 wks after last infusion

• Infusion 1: Maximum Concentration (Cmax) Value

  2 hours

Study Arms (1)

pegloticase

EXPERIMENTAL

All study participants received intravenous pegloticase at dose of 8 mg, administered every 21 days for a maximum of 5 doses. There was no control group for this open label study.

Biological: Pegloticase

Interventions

Pegloticase BIOLOGICAL

8 mg of Pegloticase administered IV every 3 weeks; total number of infusions is 5

Also known as: PEG-uricase, PEGylated recombinant mammalian urate oxidase

pegloticase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years
• Symptomatic gout
• Serum uric acid \>7 mg/dL
• Intolerance of, or inadequate response to, conventional therapy for gout
• Women of childbearing potential must have a negative serum pregnancy test and must use an approved birth control method

You may not qualify if:

• End stage renal failure that requires dialysis
• Concurrent use of uric-acid lowering agents
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• A history of anaphylactic reaction to a recombinant protein
• Concurrent use of immunosuppressive therapy (except as needed for prevention of rejection of a transplanted organ, or prednisone at 10 mg a day or less for treatment of gout flares)
• A medical or psychological condition which, in the opinion of the investigator, might create undue risk to the subject

Sponsors & Collaborators

• John Sundy: lead
• Savient Pharmaceuticals: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (5)

• Kelly SJ, Delnomdedieu M, Oliverio MI, Williams LD, Saifer MGP, Sherman MR, Coffman TM, Johnson GA, Hershfield MS. Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase. J Am Soc Nephrol. 2001 May;12(5):1001-1009. doi: 10.1681/ASN.V1251001.

  PMID: 11316859 BACKGROUND

• Sundy JS, Ganson N, Kelly SJ, Scarlett EL, Hershfield MS. A Phase I Study of PEGylated Uricase (Puricase®) in Subjects with Gout. Arthritis Rheum 50(9):S337-S338. 2004

  BACKGROUND

• Ganson NJ, Kelly SJ, Scarlett E, Sundy JS, Hershfield MS. Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase. Arthritis Res Ther. 2006;8(1):R12. doi: 10.1186/ar1861.

  PMID: 16356199 BACKGROUND

• Hershfield MS, Roberts LJ 2nd, Ganson NJ, Kelly SJ, Santisteban I, Scarlett E, Jaggers D, Sundy JS. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14351-6. doi: 10.1073/pnas.1001072107. Epub 2010 Jul 26.

  PMID: 20660758 RESULT

• Hershfield MS, Ganson NJ, Kelly SJ, Scarlett EL, Jaggers DA, Sundy JS. Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients. Arthritis Res Ther. 2014 Mar 7;16(2):R63. doi: 10.1186/ar4500.

  PMID: 24602182 DERIVED

MeSH Terms

Conditions

Gout

Interventions

Pegloticase

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: John S. Sundy, MD, PhD
• Organization: Duke University Medical Center

john.sundy@duke.edu

919-684-2347

Study Officials

• John S. Sundy, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 24, 2005
• First Posted: May 25, 2005
• Study Start: December 1, 2004
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: October 3, 2014
• Results First Posted: January 18, 2013

Record last verified: 2014-09

Locations

US (1)