REduCing Immunogenicity to PegloticasE (RECIPE) Study
Condition: Gout Chronic
Intervention: Pegloticase 8 MG/ML [Krystexxa]; MMF; Placebo; Pegloticase 8 MG/ML [Krystexxa]
Intervention description: Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.; Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.; Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.; Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase II, double blind, placebo controlled multisite proof-of-concept trial in subjects initiating pegloticase for treatment of chronic gout
Masking: Double (Participant, Investigator)
Masking description: Double blind
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The
      investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to
      investigate the question of whether a short course of immune modulating therapy with
      mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase
      and ensure patients afflicted with chronic refractory gout have better treatment outcomes and
      improved quality of life.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women > 18 years of age

          -  Diagnosed with chronic refractory gout*

               -  Defined as: Persons whose signs and symptoms are inadequately controlled with
                  urate lowering therapy (e.g. xanthine oxidase inhibitors or uricosuric agents) at
                  a medically appropriate dose or for whom these drugs are contraindicated.

        Exclusion Criteria:

          -  Any serious acute bacterial infection (2 weeks prior to Visit 1), unless treated and
             completely resolved with antibiotics

          -  Severe chronic or recurrent bacterial infections (such as recurrent pneumonia, chronic
             bronchiectasis)

          -  Current immunocompromised condition, including current or chronic treatment with
             immunosuppressive agents

          -  Subjects at risk for tuberculosis. Specifically, subjects with: i) current clinical,
             radiographic or laboratory evidence of active or latent TB; ii) a history of active TB
             within the last 3 years even if it was treated; iii) a history of active TB greater
             than 3 years ago unless there is documentation that the prior anti-TB treatment was
             appropriate in duration and type

          -  Known Hepatitis B surface antigen-positive or Hepatitis B DNA positive subjects

          -  Known Hepatitis C RNA-positive subjects

          -  Human Immunodeficiency Virus (HIV) infection

          -  G6PD deficiency (tested at Screening Visit 1)

          -  Severe chronic renal impairment (glomerular filtration rate [GFR] <25 mL/min/1.73 m2)
             or currently on dialysis

          -  Subjects having any transplant surgery requiring maintenance immunosuppressive therapy

          -  Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute
             coronary syndrome (myocardial infarction or unstable angina), or hospitalization for
             congestive heart failure within 3 months of screening or uncontrolled blood pressure
             (>160/100 mm Hg) at baseline (Screening Visit 1 and Week 0/Baseline visits)

          -  Participants who are pregnant, planning to become pregnant, breastfeeding, or not on
             an effective form of birth control (defined in Study Protocol section 7.1)

          -  Prior treatment with pegloticase, another recombinant uricase, or concomitant therapy
             with a polyethylene glycol (PEG)-conjugated drug

          -  Known allergy to pegylated products or history of anaphylactic reaction to a
             recombinant protein or porcine product

          -  Subjects in whom MMF treatment is contraindicated or considered inappropriate

          -  Recipient of an investigational drug within 4 weeks prior to study drug administration
             or plans to take an investigational agent during the study

          -  Current liver disease as determined by alanine transaminase ALT or aspartate
             transaminase (AST) levels >3 times upper limit of normal

          -  Currently receiving treatment for ongoing cancer, excluding non-melanoma skin cancer

          -  History of malignancy within 5 years other than skin cancer or in situ carcinoma of
             cervix

          -  Uncontrolled hyperglycemia with a plasma glucose value >240 mg/dL at screening

          -  Diagnosed osteomyelitis

          -  Individuals with hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) deficiency
             such as Lesch-Nyhan and Kelley-Seegmiller syndrome

          -  Not good candidate for the study based on opinion of the Investigator (e.g., cognitive
             impairment) that might create undue risk to the participant or interfere with the
             participant's ability to comply with the protocol requirements, or to complete the
             study