Trial Outcomes & Findings for 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 (NCT NCT06229145)

Last Updated: 2026-07-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

262 participants

Primary outcome timeframe

Month 6 (Weeks 20, 21, 22, 23, and 24)

Results posted on

2026-07-01

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Pegloticase 8mg Q2W + MTX Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.
Overall Study STARTED	130	131
Overall Study Received at Least 1 Dose of Pegloticase	130	131
Overall Study COMPLETED	113	113
Overall Study NOT COMPLETED	17	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Pegloticase 8mg Q2W + MTX Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.
Overall Study Lost to Follow-up	2	2
Overall Study Participant decision	15	16

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pegloticase 8mg Q2W + MTX n=130 Participants Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX n=131 Participants Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Total n=261 Participants Total of all reporting groups
Age, Continuous	56.4 years STANDARD_DEVIATION 10.6 • n=9 Participants	53.2 years STANDARD_DEVIATION 11.6 • n=27 Participants	54.8 years STANDARD_DEVIATION 11.2 • n=267 Participants
Sex: Female, Male Female	7 Participants n=9 Participants	6 Participants n=27 Participants	13 Participants n=267 Participants
Sex: Female, Male Male	123 Participants n=9 Participants	125 Participants n=27 Participants	248 Participants n=267 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	58 Participants n=9 Participants	55 Participants n=27 Participants	113 Participants n=267 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=9 Participants	70 Participants n=27 Participants	137 Participants n=267 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=9 Participants	6 Participants n=27 Participants	11 Participants n=267 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=9 Participants	2 Participants n=27 Participants	3 Participants n=267 Participants
Race/Ethnicity, Customized Asian	6 Participants n=9 Participants	8 Participants n=27 Participants	14 Participants n=267 Participants
Race/Ethnicity, Customized Black or African American	30 Participants n=9 Participants	20 Participants n=27 Participants	50 Participants n=267 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	1 Participants n=27 Participants	1 Participants n=267 Participants
Race/Ethnicity, Customized White	91 Participants n=9 Participants	100 Participants n=27 Participants	191 Participants n=267 Participants
Race/Ethnicity, Customized Other	1 Participants n=9 Participants	0 Participants n=27 Participants	1 Participants n=267 Participants

PRIMARY outcome

Timeframe: Month 6 (Weeks 20, 21, 22, 23, and 24)

Population: FAS included all participants who received at least 1 dose of pegloticase.

Outcome measures

Outcome measures
Measure	Pegloticase 8mg Q2W + MTX n=130 Participants Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX n=131 Participants Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6	70.8 percentage of participants Interval 62.2 to 78.4	56.5 percentage of participants Interval 47.6 to 65.1

SECONDARY outcome

Timeframe: Baseline, Week 24

Outcome measures

Outcome data not reported

Adverse Events

MTX Run-In Period: All Participants

Serious events: 2 serious events

Other events: 61 other events

Deaths: 0 deaths

Pegloticase 8mg Q2W + MTX

Serious events: 4 serious events

Other events: 66 other events

Deaths: 0 deaths

Pegloticase 16mg Q4W + MTX

Serious events: 9 serious events

Other events: 87 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MTX Run-In Period: All Participants n=306 participants at risk All Participants received oral MTX 15 mg once weekly for 4 weeks during the run-in period.	Pegloticase 8mg Q2W + MTX n=130 participants at risk Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX n=131 participants at risk Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.77% 1/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Cardiac disorders Atrial fibrillation	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Cardiac disorders Cardiac failure congestive	0.33% 1/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.77% 1/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Immune system disorders Anaphylactic reaction	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.77% 1/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	2.3% 3/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Infections and infestations Herpes zoster	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Infections and infestations Pneumonia	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Infections and infestations Pneumonia influenzal	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Infections and infestations Pyelonephritis	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.77% 1/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.33% 1/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Vascular disorders Orthostatic hypotension	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.00% 0/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	0.76% 1/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.

Other adverse events

Other adverse events
Measure	MTX Run-In Period: All Participants n=306 participants at risk All Participants received oral MTX 15 mg once weekly for 4 weeks during the run-in period.	Pegloticase 8mg Q2W + MTX n=130 participants at risk Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 8 mg administered IV Q2W from Day 1 through Week 22 and MTX 15 mg administered orally once weekly during the 24-week double-blind period.	Pegloticase 16mg Q4W + MTX n=131 participants at risk Participants received oral MTX 15 mg once weekly for 4 weeks during the run in period, followed by pegloticase 16 mg administered IV Q4W from Day 1 through Week 20 and matching placebo from Week 2 through Week 22 (to maintain the blind) and MTX 15 mg administered orally once weekly during the 24-week double-blind period.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	6.9% 9/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	6.9% 9/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Metabolism and nutrition disorders Gout	19.9% 61/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	47.7% 62/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	61.8% 81/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/306 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	7.7% 10/130 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.	2.3% 3/131 • For all-cause mortality: from signing of inform consent form (ICF) through database lock (DBL) for primary analysis (up to Week 24); For Serious adverse events and other adverse events: from first dose of MXT through DBL for the primary analysis (up to Week 24). Participants who completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1, except 1 participant was randomized in error and did not receive pegloticase. Serious adverse events and other adverse events are reported for all participants who received at least one dose of trial drug. All-cause mortality is reported for all participants enrolled in the trial.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER