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
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.
Condition
- Gout
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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.
Study Design
- Phase
- Phase 4
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
Recruiting Locations
The University of Alabama at Birmingham (UAB)
Birmingham, Alabama 35233
Birmingham, Alabama 35233
More Details
- Status
- Recruiting
- Sponsor
- Amgen
Detailed Description
Acquired from Horizon in 2024.