Gout
Conditions
Keywords
Uncontrolled Gout, pegloticase, Krystexxa, Methotrexate, Chronic Gout
Brief summary
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.
Detailed description
Acquired from Horizon in 2024.
Interventions
BIOLOGICALPegloticase
IV infusion
DRUGMethotrexate
Oral
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6 | Month 6 (Weeks 20, 21, 22, 23, and 24) | Responders were defined as participants who achieved and maintained sUA levels below 6 mg/dL for at least 80% of the time during Month 6. Responders who met sUA discontinuation criteria (2 consecutive sUA \> 6 mg/dL), regardless of treatment status were considered non-responders. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Complete Resolution of ≥ 1 Tophus at Week 24 in Participants With Tophi at Baseline | Baseline, Week 24 |
Countries
United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
Participants were enrolled at 51 trial centers in United States of America from 18 March 2024. The primary analysis data is presented for the double-blind period up to 30 July 2025, with a database snapshot date of 26 September 2025; the trial is ongoing, and data from the open-label period will be posted with the final analysis. A 4 week methotrexate (MTX) run in period with weekly dose of 15 mg was used to identify screening failures due to MTX intolerance.
Pre-assignment details
306 participants started and only 262 participants completed the run-in period. Participants who completed run-in were randomized 1:1 to receive either pegloticase 16 mg intravenously (IV) every 4 weeks (Q4W) or pegloticase 8 mg IV every two weeks (Q2W) in 24-week double-blind period. Participant flow is presented for 261 participants in Full analysis set (FAS) who received ≥1 dose of pegloticase. 1 participant was randomized in error and did not receive pegloticase and was excluded from FAS.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants |
| Race/Ethnicity, Customized Black or African American | 20 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 191 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 306 | 0 / 130 | 0 / 131 |
| other Total, other adverse events | 61 / 306 | 66 / 130 | 87 / 131 |
| serious Total, serious adverse events | 2 / 306 | 4 / 130 | 9 / 131 |
Outcome results
None listed