Purpose

The purpose of this study is to evaluate the effect of a high zone tolerizing regimen of pegloticase on clinical outcome, as defined by an serum uric acid level <6 mg/dL, in patients with chronic, refractory gout.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Adult (age ≥18 years) men and women of non-childbearing potential, with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated.
  2. Hyperuricemic - Screening visit SUA must be >6 mg/dL
  3. On gout flare prophylactic regimen for 7 days prior to the first dose.
  4. 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)

Exclusion Criteria

  1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (confirmed at Screening visit)
  2. Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute coronary syndrome (ACS) (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 and pre-dose at Week 1 visit )
  3. Women of childbearing potential defined as:
  4. Pre- or perimenopausal (<24 months of natural [spontaneous] amenorrhea).
  5. <6 weeks after surgical bilateral oophorectomy with or without hysterectomy.
  6. Prior treatment with pegloticase or another recombinant uricase
  7. Prior treatment or concomitant therapy with a polyethylene glycol (PEG) conjugated drug
  8. Known allergy to PEG products or history of anaphylactic reaction to a recombinant protein or porcine product
  9. Concurrent treatment with urate lowering agents (ULAs), such as allopurinol and febuxostat. Patients treated with these medications must discontinue treatment 7 days prior to the first dose of study drug
  10. Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study
  11. Current liver disease as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels >3 times upper limit of normal (ULN)
  12. History of malignancy within 5 years other than basal cell skin cancer or carcinoma in situ of the cervix
  13. Has any other medical or psychological condition which, in the opinion of the Investigator, might create undue risk to the patient or interfere with the patient's ability to comply with the protocol requirements, or to complete the study
  14. Solid organ transplant recipients
  15. Uncontrolled hyperglycemia with a plasma glucose value >240 mg/dL at screening
  16. Currently on dialysis

Additional Exclusion Criteria for Imaging Sub-study Only

15. Contraindication to receiving a gadolinium-based contrast agent (GBCA) or > 2 previous lifetime exposures to a GBCA

16. Implanted pacemaker, certain older intracranial aneurysm clips, cochlear implants, certain prosthetic devices, implanted drug infusion pumps, neurostimulators, bone-growth stimulators, certain intrauterine contraceptive devices, or any other type of iron-based metal implants.

17. Any internal metallic objects such as bullets or shrapnel, as well as most surgical clips, pins, plates, screws, metal sutures, or wire mesh.

Additional Exclusion Criteria for FDG-PET-CT Sub-study Only

18. Contraindication to FDG

Additional Exclusion Criteria for Pegloticase and AZA Therapy Arm Only

19. Any active serious bacterial infection (2 weeks prior to screening) requiring antibiotic treatment

20. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia, chronic bronchiectasis

21. Current immunocompromised condition, including current or chronic treatment with systemic immunosuppressive agents (e.g., prednisone or equivalent dose >510 mg/day)

22. At risk for tuberculosis. Specifically, subjects with: a) current clinical, radiographic, or laboratory evidence of active or latent tuberculosis; b) a history of active tuberculosis within the last 31 years even if it was treated; c) a history of active tuberculosis >31 years ago unless there is documentation that the prior anti-tuberculosis treatment was appropriate in duration and type

23. Known history of hepatitis B surface antigen-positivity or hepatitis B DNA positivity

24. Known history of hepatitis C RNA-positivity

25. Known history of human immunodeficiency virus positivity

26. Severe chronic renal impairment (glomerular filtration rate <25 mL/min/1.73 m2)

27. AZA treatment is contraindicated or considered inappropriate

28. Subject has a homozygous or heterozygous thiopurine methyltransferase (TPMT) variant genotype

29. Diagnosis of osteomyelitis

30. Known hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome

31. Concurrent use of a xanthine oxidase inhibitor

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pegloticase regimen <120 kg - Main Study
Subjects weighing <120 kg will receive a tolerizing dose of pegloticase 8 mg IV weekly for the first 3 weeks of dosing followed by an 8 mg IV dose every 2 weeks for a total of 10 doses.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
Experimental
Pegloticase regimen ≥120kg
Subjects weighing ≥ 120 kg will be sequentially assigned to 1 of 3 different loading doses (8, 12, and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
Experimental
Pegloticase PK Sub-Study
Subjects weighing <120 kg and ≥120 kg will be assigned to 1 of 2 different loading doses (12 and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses. Subjects will have multiple blood sampled for PK levels over the 17 week dosing period.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
Experimental
Pegloticase Imaging Sub-Study
A subset of subjects participating in the Main Study and weighing <120 kg will have dual-energy computed tomography (DECT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) performed at Screen and at Week 17.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
Experimental
Pegloticase FDG-PET-CT Sub-Study
A subset of subjects participating in the Main Study and weighing <120 kg will have fluorodeoxyglucose-positron emission tomography (FDG-PET-CT) to evaluate carotid and aortic (chest) atherosclerosis at Screen and at Week 17.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
Experimental
Pegloticase and Azathioprine
Subjects weighing <120 kg will receive azathioprine (AZA) daily for a 2-week run-in period, followed by daily AZA plus pegloticase 8 mg IV every 2 weeks through Week 25 for a total of 13 doses.
  • Biological: Pegloticase
    Pegloticase, IV
    Other names:
    • Krystexxa
  • Drug: Azathioprine
    Azathioprine (1.25 mg/kg, followed by 2.5 mg/kg) oral, daily
    Other names:
    • Imuran

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467

More Details

NCT ID
NCT02598596
Status
Recruiting
Sponsor
Ampel BioSolutions, LLC

Study Contact

Maggie Pugh, MS
404-892-7002
mpugh@ind2results.com

Detailed Description

This is an exploratory open-label, multicenter study to evaluate the effectiveness of a 16-week high zone tolerance regimen of pegloticase on response to therapy (serum uric acid <6 mg/dL) with this drug in adult hyperuricemic patients with gout refractory to conventional therapy.

Eligible subjects will receive 1 of 3 different loading doses (8, 12, and 16 mg) on Study Day 1, and then receive 8 mg on Week 2 and 3, followed by 8 mg every 2 weeks through Week 17 for a total of 10 doses.

Subjects will be monitored for efficacy and safety endpoints through Week 17. Subjects will also have blood drawn for pegloticase levels prior to each dose on Weeks 2, 3, 5, 7, 9, 11, 13,15, and 17. Following Study Week 17, subjects will have an option to continue dosing for an additional 8 weeks.

A subset of subjects will participate in additional pharmacokinetic (PK) assessments.

The study duration, per enrolled patient, will be approximately 26 weeks including a 2-week screening period, a 16-week treatment period (end of treatment [EOT] visit Week 17), and an optional 8-week dosing extension.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.