A Trial to Investigate the Non-inferiority of Pegloticase Administered Every 4 Weeks (Q4W) With MTX Compared With Every 2 Weeks (Q2W) With MTX in Participants With Uncontrolled Refractory Gout

Launched by AMGEN · Jan 19, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness and safety of a medication called pegloticase for people with uncontrolled gout, which is a form of arthritis that causes painful swelling in the joints. The trial is comparing two different schedules for giving the medication: every four weeks versus every two weeks, both combined with another drug called methotrexate (MTX). Researchers want to see if giving pegloticase once every four weeks is just as effective as giving it every two weeks over a 24-week period. Participants will be monitored for their response to the treatment, particularly looking for a stable level of uric acid in the blood, which is important for managing gout symptoms.

To be eligible for this trial, participants must be at least 18 years old and have persistent gout that has not responded well to other treatments. This includes having high levels of uric acid in their blood and experiencing symptoms of gout. Participants should be willing to stop certain other gout medications before starting the trial. Throughout the study, participants will receive either the medication or a placebo (a non-active treatment) in a way that keeps them and their doctors unaware of which one they are receiving (this is called a double-blind study). After the initial 24 weeks, there will be an additional 24-week period where everyone will receive the pegloticase treatment. It’s important for potential participants to discuss any health issues or medications they are currently taking with their healthcare provider to ensure they meet the criteria for the trial.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Adult men or women ≥ 18 years of age
• 2. Uncontrolled gout, defined as meeting the following criteria:
• • Hyperuricemia during the Screening Period, defined as sUA ≥ 7 mg/dL, and;
• • Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or participant interview, and;
• • Symptoms of gout
• • 3. Willing to discontinue any oral ULT for at least 7 days prior to MTX dosing at Week -4 and continue not receiving any oral ULT when receiving pegloticase/placebo for pegloticase infusions
• • 4. Women of childbearing potential must have negative serum/urine pregnancy tests during screening and Week -4.
• • 5. Men who are not vasectomized must agree to use appropriate contraception, so as to not impregnate a female partner of reproductive potential during the trial.
• Exclusion Criteria:
• • 1. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis
• • 2. Current or chronic treatment with systemic immunosuppressive agents, such as MTX, azathioprine or mycophenolate mofetil; prednisone \> 10 mg/day or equivalent dose of other corticosteroid on a chronic basis (3 months or longer)
• • 3. History of any transplant surgery requiring maintenance immunosuppressive therapy
• • 4. Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity
• • 5. Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative
• • 6. Known history of human immunodeficiency virus (HIV) positivity
• • 7. G6PD deficiency (quantitative test at the Screening Visit centrally or locally)
• • 8. Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina) or uncontrolled blood pressure (\> 160/100 mmHg) prior to Week -4
• • 9. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner or not on an effective form of birth control, as determined by the Investigator
• • 10. Prior treatment with pegloticase, another recombinant uricase (rasburicase) or concomitant therapy with a PEG-conjugated drug
• • 11. Unable to tolerate MTX 15 mg orally during the MTX Run-in Period
• • 12. Chronic liver disease
• • 13. White blood cell count \< 4,000/μL, hematocrit \< 32% or platelet count \< 75,000/μL
• • 14. Currently receiving systemic or radiologic treatment for ongoing cancer
• • 15. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix
• • 16. Diagnosis of osteomyelitis
• • 17. Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome
• • 18. A known intolerance to all protocol-standard gout flare prophylaxis regimens (i.e., participant must be able to tolerate at least 1 of the following: colchicine and/or non-steroidal anti-inflammatory drugs and/or low-dose prednisone ≤ 10 mg/day)
• • 19. Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.