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

Study Purpose

The study consists of 24-week double-blind trial to evaluate the non-inferiority of the efficacy and safety of pegloticase Q4W with MTX versus pegloticase Q2W with MTX, followed by a 24-week open-label extension of pegloticase Q4W with MTX, in participants with uncontrolled refractory gout. The main objective of the study is to evaluate the effect of pegloticase 16 mg administered Q4W with MTX versus pegloticase 8 mg administered Q2W with MTX, on the response rate during Month 6, as measured by the sustained normalization of sUA to < 6 mg/dL for at least 80% of the time.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06229145
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 4
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Amgen
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	MD
Principal Investigator Affiliation	Amgen
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Gout
Study Website:	View Trial Website

Additional Details

Acquired from Horizon in 2024.

Arms & Interventions

Arms

Experimental: Pegloticase + Methotrexate Q4W

16 mg pegloticase will be administered intravenously every 4 weeks for 24 weeks during double blind treatment and 24 weeks during open label.

Experimental: Pegloticase + Methotrexate Q2W

8 mg pegloticase will be administered intravenously every 2 weeks for 24 weeks during double blind treatment and 16 mg pegloticase every 4 weeks for 24 weeks during open label.

Interventions

Biological: - Pegloticase

IV infusion

Drug: - Methotrexate

Oral

Contact a Trial Team

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Birmingham, Alabama

Status

Recruiting

Address

The University of Alabama at Birmingham (UAB)

Birmingham, Alabama, 35233

Site Contact

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