Trial Outcomes & Findings for A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL) (NCT NCT04762498)
NCT ID: NCT04762498
Last Updated: 2026-05-19
Results Overview
Responders are defined as participants achieving and maintaining sUA \< 6 mg/dL for at least 80% of the time during Month 6. Participants meeting the sUA discontinuation criteria (pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 1 Visit) were counted as non-responders.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
54 participants
Primary outcome timeframe
Month 6 (Weeks 20, 21, 22, 23, and 24)
Results posted on
2026-05-19
Participant Flow
A total of 54 participants were enrolled into this trial in the United States between March 2021 and December 2023.
This trial included a screening period of up to 5 weeks, a methotrexate (MTX) run-in period of 4 weeks, a pegloticase + MTX treatment period from Day 1 to Week 24, and an optional extension period from Week 24 to Week 48. A safety follow-up visit occurred 4 weeks after the last pegloticase infusion or MTX dose.
Participant milestones
| Measure |
MTX Run-in
Participants received 15 mg MTX orally once weekly for 4 weeks prior to randomization.
|
Pegloticase 16 mg + MTX
Following the run-in period, participants were randomized to receive a 16 mg intravenous (IV) dose of pegloticase every 4 weeks (Q4W) with 15 mg MTX weekly.
|
Pegloticase 30 mg + MTX
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|---|
|
MTX Run-in
STARTED
|
54
|
0
|
0
|
|
MTX Run-in
COMPLETED
|
51
|
0
|
0
|
|
MTX Run-in
NOT COMPLETED
|
3
|
0
|
0
|
|
Pegloticase + MTX Treatment Period
STARTED
|
0
|
25
|
26
|
|
Pegloticase + MTX Treatment Period
COMPLETED
|
0
|
22
|
24
|
|
Pegloticase + MTX Treatment Period
NOT COMPLETED
|
0
|
3
|
2
|
|
Optional Extension Period
STARTED
|
0
|
17
|
19
|
|
Optional Extension Period
COMPLETED
|
0
|
16
|
15
|
|
Optional Extension Period
NOT COMPLETED
|
0
|
1
|
4
|
Reasons for withdrawal
| Measure |
MTX Run-in
Participants received 15 mg MTX orally once weekly for 4 weeks prior to randomization.
|
Pegloticase 16 mg + MTX
Following the run-in period, participants were randomized to receive a 16 mg intravenous (IV) dose of pegloticase every 4 weeks (Q4W) with 15 mg MTX weekly.
|
Pegloticase 30 mg + MTX
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|---|
|
MTX Run-in
Screen Failure
|
3
|
0
|
0
|
|
Pegloticase + MTX Treatment Period
Death
|
0
|
1
|
0
|
|
Pegloticase + MTX Treatment Period
Lost to Follow-up
|
0
|
1
|
0
|
|
Pegloticase + MTX Treatment Period
Withdrawal by Subject
|
0
|
1
|
2
|
|
Optional Extension Period
Lost to Follow-up
|
0
|
1
|
0
|
|
Optional Extension Period
Withdrawal by Subject
|
0
|
0
|
4
|
Baseline Characteristics
A Phase 4, Open-label Study of KRYSTEXXA® (Pegloticase) Co-administered With Methotrexate (MTX) in Patients With Uncontrolled Gout (FORWARD OL)
Baseline characteristics by cohort
| Measure |
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.2 years
STANDARD_DEVIATION 9.56 • n=30 Participants
|
55.8 years
STANDARD_DEVIATION 8.74 • n=30 Participants
|
55.0 years
STANDARD_DEVIATION 9.09 • n=60 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=30 Participants
|
1 Participants
n=30 Participants
|
3 Participants
n=60 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=30 Participants
|
25 Participants
n=30 Participants
|
48 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
16 Participants
n=30 Participants
|
10 Participants
n=30 Participants
|
26 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=30 Participants
|
16 Participants
n=30 Participants
|
25 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=30 Participants
|
2 Participants
n=30 Participants
|
5 Participants
n=60 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=30 Participants
|
24 Participants
n=30 Participants
|
45 Participants
n=60 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=30 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=60 Participants
|
PRIMARY outcome
Timeframe: Month 6 (Weeks 20, 21, 22, 23, and 24)Population: Intent-to-treat (ITT) analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
Responders are defined as participants achieving and maintaining sUA \< 6 mg/dL for at least 80% of the time during Month 6. Participants meeting the sUA discontinuation criteria (pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 1 Visit) were counted as non-responders.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Percentage of Participants Who Were Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
|
73.1 percentage of participants
Interval 52.2 to 88.4
|
68.0 percentage of participants
Interval 46.5 to 85.1
|
PRIMARY outcome
Timeframe: Day 1 to Week 24Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
The number of participants who had pre-Infusion sUA ≥ 6 mg/dL post-day 1 pegloticase infusion were included in this analysis. The date of the first pre-infusion sUA ≥ 6 mg/dL was the event date. Participants who did not have the event were censored at the date of the last collected pre-infusion sample with non-missing sUA result. Participants who never achieved sUA \< 6 mg/dL were excluded from the analysis.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=8 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=8 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Time to First sUA ≥6 mg/dL After First Achieving sUA <6 mg/dL, From the First Pegloticase Infusion Until Week 24
|
45.1 days
Standard Deviation 37.19
|
51.5 days
Standard Deviation 39.49
|
SECONDARY outcome
Timeframe: Post infusion on Day 1, at Weeks 1, 2, 3 and pre-dose at Week 4Population: PK analysis set: All enrolled participants who received at least 1 dose of pegloticase and had a post-pegloticase sample evaluable for PK analysis.
Noncompartmental Pharmacokinetic (PK) parameters of pegloticase were estimated using concentration data after the first dose (including Week 4 predose concentration data) using Phoenix WinNonlin® software. The linear/log trapezoidal rule was used in conjunction with the appropriate noncompartmental model, with input values for dose level, dosing time, serum concentration, and corresponding real-time values, based on drug dosing times whenever possible. Below limit of quantification (BLQ) values prior to the first quantifiable concentration were set to 0; BLQ values at all other time points were set to half the lower limit of quantification (LLOQ) (0.025 µg/mL).
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=22 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=23 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Maximum Concentration (Cmax) of Pegloticase
|
11 μg/mL
Geometric Coefficient of Variation 33
|
6.09 μg/mL
Geometric Coefficient of Variation 33
|
SECONDARY outcome
Timeframe: Post infusion on Day 1, at Weeks 1, 2, 3 and pre-dose at Week 4Population: PK analysis set: All enrolled participants who received at least 1 dose of pegloticase and had a post-pegloticase sample evaluable for PK analysis.
Noncompartmental PK parameters of pegloticase were estimated using concentration data after the first dose (including Week 4 predose concentration data) using Phoenix WinNonlin® software. The linear/log trapezoidal rule was used in conjunction with the appropriate noncompartmental model, with input values for dose level, dosing time, serum concentration, and corresponding real-time values, based on drug dosing times whenever possible. BLQ values prior to the first quantifiable concentration were set to 0; BLQ values at all other time points were set to half LLOQ (0.025 µg/mL).
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=22 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=23 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Area Under the Concentration- Time Curve From Time 0 to Week 4 Predose of Pegloticase
|
3120 hr*μg/mL
Geometric Coefficient of Variation 25
|
1670 hr*μg/mL
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: Week 24 Pre-dosePopulation: PK analysis set: All enrolled participants who received at least 1 dose of pegloticase and had a post-pegloticase sample evaluable for PK analysis. Only participants with data available were included in this analysis.
Blood samples were collected for measurement of serum concentrations of pegloticase. The median concentration of pegloticase taken at Week 24 pre-dose was reported as the Ctrough concentration at Week 24.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=16 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=16 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Trough Serum Concentration (Ctrough) of Pegloticase at Week 24 Pre-dose
|
2.76 μg/mL
Interval 2.1 to 3.11
|
1.33 μg/mL
Interval 0.932 to 2.39
|
SECONDARY outcome
Timeframe: Pre-infusion on Day 1, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
The percentage of participants with pre-infusion sUA \<6 mg/dL at each scheduled infusion visit, regardless of treatment status, was presented.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 28 - Pre-infusion
|
88.9 percentage of participants
Interval 65.3 to 98.6
|
100 percentage of participants
Interval 80.5 to 100.0
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 32 - Pre-infusion
|
88.9 percentage of participants
Interval 65.3 to 98.6
|
94.1 percentage of participants
Interval 71.3 to 99.9
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 4 - Pre-infusion
|
84.6 percentage of participants
Interval 65.1 to 95.6
|
83.3 percentage of participants
Interval 62.6 to 95.3
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 8 - Pre-infusion
|
84.6 percentage of participants
Interval 65.1 to 95.6
|
78.3 percentage of participants
Interval 56.3 to 92.5
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 12 - Pre-infusion
|
87.5 percentage of participants
Interval 67.6 to 97.3
|
86.4 percentage of participants
Interval 65.1 to 97.1
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 16 - Pre-infusion
|
83.3 percentage of participants
Interval 62.6 to 95.3
|
85.7 percentage of participants
Interval 63.7 to 97.0
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 20 - Pre-infusion
|
82.6 percentage of participants
Interval 61.2 to 95.0
|
90.5 percentage of participants
Interval 69.6 to 98.8
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 24 - Pre-infusion
|
82.6 percentage of participants
Interval 61.2 to 95.0
|
85.7 percentage of participants
Interval 63.7 to 97.0
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 36 - Pre-infusion
|
88.2 percentage of participants
Interval 63.6 to 98.5
|
88.2 percentage of participants
Interval 63.6 to 98.5
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 40 - Pre-infusion
|
88.2 percentage of participants
Interval 63.6 to 98.5
|
100 percentage of participants
Interval 78.2 to 100.0
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Week 44 - Pre-infusion
|
86.7 percentage of participants
Interval 59.5 to 98.3
|
100 percentage of participants
Interval 79.4 to 100.0
|
|
Percentage of Participants With Pre-infusion sUA <6 mg/dL at Each Scheduled Visit
Day 1 - Pre-infusion
|
3.8 percentage of participants
Interval 0.1 to 19.6
|
0 percentage of participants
Interval 0.0 to 13.7
|
SECONDARY outcome
Timeframe: Day 1 to Week 24 and Day 1 to Week 48Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
The AUC from Day 1 to Week 24 and from Day 1 to Week 48 was calculated as time-adjusted AUC derived using the trapezoidal rule divided by the number of total days in the given period. The AUC from Day 1 to Week 48 was only calculated for participants who continued in the optional treatment period from Week 24 to Week 48.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Area Under the sUA Concentration vs Time Curve From Day 1 to Week 24 and Day 1 to Week 48
Day 1 to Week 24
|
1.3 mg/dL
Standard Deviation 2.24
|
1.4 mg/dL
Standard Deviation 2.47
|
|
Area Under the sUA Concentration vs Time Curve From Day 1 to Week 24 and Day 1 to Week 48
Day 1 to Week 48
|
0.8 mg/dL
Standard Deviation 2.24
|
0.3 mg/dL
Standard Deviation 0.78
|
SECONDARY outcome
Timeframe: Day 1 to Week 24 and Day 1 to Week 48Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
The percentage of time that participants sustained sUA \< 6 mg/dL was derived using linear interpolation across all observed data points between Day 1 and the end of each analysis period. The percentage of time during a given period is the time that sUA \< 6 mg/dL divided by the total time from the first to the last scheduled visit in the given period.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Percentage of Time Participants Sustained sUA < 6 mg/dL From Day 1 to Week 24 or Day 1 to Week 48
Day 1 to Week 24
|
87.9 percentage of time
Standard Deviation 22.76
|
87.3 percentage of time
Standard Deviation 25.55
|
|
Percentage of Time Participants Sustained sUA < 6 mg/dL From Day 1 to Week 24 or Day 1 to Week 48
Day 1 to Week 48
|
91.4 percentage of time
Standard Deviation 25.57
|
98.5 percentage of time
Standard Deviation 4.03
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Weeks 2, 4, 8, 16, 24, 36 and 48Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
Pegloticase immunogenicity was assessed by incidence of anti-poly (Ethylene Glycol) (PEG) and anti-uricase immunoglobulin G (IgG) antibodies. The percentage of participants who were treatment-emergent anti-drug antibody (ADA) positive is presented below. Participants were considered treatment-emergent ADA positive if they were ADA negative at the data collection timepoint of Day 1 (Baseline) and ADA positive at one of the specified post-dose timepoints.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 2
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 4
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 8
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 16
|
4.3 percentage of participants
|
23.8 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 24
|
8.3 percentage of participants
|
18.2 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 36
|
16.7 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Anti-uricase Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 48
|
6.7 percentage of participants
|
6.7 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Weeks 2, 4, 8, 16, 24, 36 and 48Population: ITT analysis set: All enrolled participants who had at least 1 scheduled assessment on Day 1.
Pegloticase immunogenicity was assessed by incidence of anti-PEG and anti-uricase IgG antibodies. The percentage of participants who were treatment-emergent ADA positive is presented below. Participants were considered treatment-emergent ADA positive if they were ADA negative at the data collection timepoint of Day 1 (Baseline) and ADA positive at one of the specified post-dose timepoints.
Outcome measures
| Measure |
Pegloticase 30 mg + MTX
n=26 Participants
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase 16 mg + MTX
n=25 Participants
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 2
|
12.0 percentage of participants
|
13.0 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 4
|
15.4 percentage of participants
|
24.0 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 8
|
42.3 percentage of participants
|
25.0 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 16
|
26.1 percentage of participants
|
14.3 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 24
|
25.0 percentage of participants
|
22.7 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 36
|
22.2 percentage of participants
|
17.6 percentage of participants
|
|
Percentage of Participants With Anti-PEG Antibodies at Each Scheduled Visit
Treatment-Emergent ADA Positive at Week 48
|
13.3 percentage of participants
|
6.7 percentage of participants
|
Adverse Events
MTX Run-in
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
Pegloticase 16 mg + MTX
Serious events: 3 serious events
Other events: 19 other events
Deaths: 1 deaths
Pegloticase + 30 mg MTX
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MTX Run-in
n=54 participants at risk
Participants received 15 mg MTX orally once weekly for 4 weeks prior to randomization.
|
Pegloticase 16 mg + MTX
n=25 participants at risk
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase + 30 mg MTX
n=26 participants at risk
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
4.0%
1/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
4.0%
1/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Infections and infestations
COVID-19
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
4.0%
1/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
4.0%
1/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
Other adverse events
| Measure |
MTX Run-in
n=54 participants at risk
Participants received 15 mg MTX orally once weekly for 4 weeks prior to randomization.
|
Pegloticase 16 mg + MTX
n=25 participants at risk
Following the run-in period, participants were randomized to receive a 16 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
Pegloticase + 30 mg MTX
n=26 participants at risk
Following the run-in period, participants were randomized to receive a 30 mg IV dose of pegloticase Q4W with 15 mg MTX weekly.
|
|---|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
7.7%
2/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
12.0%
3/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
11.5%
3/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
11.5%
3/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Investigations
Glomerular filtration rate decreased
|
1.9%
1/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Investigations
White blood cell count decreased
|
3.7%
2/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Metabolism and nutrition disorders
Gout
|
31.5%
17/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
72.0%
18/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
76.9%
20/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
3.8%
1/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Gastrointestinal disorders
Nausea
|
3.7%
2/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/54 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
8.0%
2/25 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
0.00%
0/26 • MTX run-in period: Week -4 to Day 1; pegloticase + MTX treatment period: Day 1 to Week 48
Serious adverse events (SAEs) and other adverse events (AEs) were reported for all participants who received at least one dose of trial drug. All-cause mortality was reported for all participants enrolled in the trial.
|
Additional Information
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