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

Gout Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00325195
• Other study ID #: C0405 & C0406
• Status: Completed
• Phase: Phase 3
• First received: May 10, 2006
• Last updated: February 24, 2011
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: February 2011
• Source: Savient Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical 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 uric acid level.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: December 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gout
• Hyperuricemia

Intervention

Other:
• placebo
placebo by intravenous infusion every 2 weeks

Biological:
• pegloticase
8 mg pegloticase by intravenous infusion

Locations

Country	Name	City	State
Canada	St. Joseph's Health Care	London	Ontario
Canada	Manitoba Clinic	Winnipeg	Manitoba
Mexico	Antiguo Hospital Civil de Guadalajara	Guadalajara	Jalisco
Mexico	Hospital Civil de Guadalajara	Guadalajara	Jalisco
Mexico	Clinica para el Diagnostico y Tratamiento de las Enfermedades Rheumaticas	Mexico	D.f.
Mexico	Hospital General de mexico	Mexico	D.f.
United States	AAMR Research Clinic	Amarillo	Texas
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	Peter A. Holt, M.D.	Baltimore	Maryland
United States	UAB Arthritis Clinical Intervention Program	Birmingham	Alabama
United States	Idaho Arthritis & Osteoporosis Center	Boise	Idaho
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	Michigan Arthritis Research Center	Brighton	Michigan
United States	Rheumatology Associates	Charleston	South Carolina
United States	The University of Chicago	Chicago	Illinois
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Arthritis Associates & Osteoporosis Center of Colorado Springs	Colorado Springs	Colorado
United States	The Ohio State University	Columbus	Ohio
United States	STAT Research, Inc.	Dayton	Ohio
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Malcom Randall VA Medical Center	Gainesville	Florida
United States	Rheumatic Disease Center	Glendale	Wisconsin
United States	Brody School of Medicine, East Carolina University	Greenville	North Carolina
United States	Physicians East, P.A.	Greenville	North Carolina
United States	Piedmont Arthritis, PA	Greenville	South Carolina
United States	Malamet & Klein, MD, PA	Hagerstown	Maryland
United States	Horizon Institute for Clinical Research	Hollywood	Florida
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	NEA Clinic	Jonesboro	Arkansas
United States	UCSD Rheumatology Division	La Jolla	California
United States	Justus J. Fiechtner, MD, PC	Lansing	Michigan
United States	David R. Mandel, MD, Inc.	Mayfield Village	Ohio
United States	Mount Sinai Medical Center	New York	New York
United States	Ocala Rheumatology Research Center	Ocala	Florida
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Arthritis & Osteoporosis Treatment Center, PA	Orange Park	Florida
United States	Mid Atlantic Research Assoc.	Philadelphia	Pennsylvania
United States	Portland Medical Associates	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Arthritis & Osteoporosis Center of South Texas	San Antonio	Texas
United States	Kaiser Permanente Medical Center, Clinical Trials Unit	San Francisco	California
United States	Pacific Arthritis Center Medical Group	Santa Maria	California
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	CentraCare Clinic	St. Cloud	Minnesota
United States	St. Petersburg Arthritis Center	St. Petersburg	Florida
United States	Rheumatology Associates of North Jersey	Teaneck	New Jersey
United States	University of Arizona Arthritis Center	Tucson	Arizona
United States	Arthritis & Osteoporosis Clinic Research Center of Central Texas	Waco	Texas
United States	Veterans Affairs Medical Center	Washington	District of Columbia
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Agilence Arthritis & Osteoporosis Medical Center	Whittier	California
United States	E. Robert Harris Medical Corporation	Whittier	California
United States	Carolina Atthritis Associates	Wilmington	North Carolina
United States	Fallon Clinic, Inc	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Savient Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Baseline and Final Visit (6 months or LOCF)	No
Secondary	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.	Months 1-3 and Months 4-6	No
Secondary	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.	Baseline and Final Visit (Month 6 or LOCF)	No
Secondary	Change in Number of Tender Joints	Change from Baseline to Month 6 (or last observation carried forward) in number of tender joints per participant	Baseline and Final Visit (Month 6 or LOCF)	No
Secondary	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.	Baseline to Final Visit (Month 6 or LOCF)	No