Safety and Efficacy Study of PEG-uricase in the Treatment of Hyperuricemic Patients With Symptomatic Gout
Condition: Gout
MeSH terms: Gout; Hyperuricemia
Intervention: placebo; pegloticase
Intervention description: placebo by intravenous infusion every 2 weeks; 8 mg pegloticase by intravenous infusion
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 225.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.