Trial Outcomes & Findings for Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy (NCT NCT04772313)
NCT ID: NCT04772313
Last Updated: 2024-06-27
Results Overview
An sUA responder is defined as a participant achieving and maintaining sUA \<6 mg/dL for at least 80% of the time during Month 6 (Weeks 20, 21, 22, 23 and 24).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
11 participants
Primary outcome timeframe
Month 6
Results posted on
2024-06-27
Participant Flow
All participants who meet the inclusion/exclusion criteria and completed the MTX Run-in Period were considered enrolled participants and received the first pegloticase infusion on Day 1. Participants who did not complete the MTX Run-in Period were considered screen failures.
Participant milestones
| Measure |
Pegloticase Plus Methotrexate
Methotrexate (MTX) 15 or 25 mg subcutaneous (SC) weekly during the 6-week MTX Run-in Period. Pegloticase 8 mg intravenous (IV) every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
MTX Run-in Period
STARTED
|
13
|
|
MTX Run-in Period
COMPLETED
|
11
|
|
MTX Run-in Period
NOT COMPLETED
|
2
|
|
Pegloticase + MTX Treatment Period
STARTED
|
11
|
|
Pegloticase + MTX Treatment Period
COMPLETED
|
5
|
|
Pegloticase + MTX Treatment Period
NOT COMPLETED
|
6
|
|
Pegloticase + MTX Extension Period
STARTED
|
1
|
|
Pegloticase + MTX Extension Period
COMPLETED
|
1
|
|
Pegloticase + MTX Extension Period
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Pegloticase Plus Methotrexate
Methotrexate (MTX) 15 or 25 mg subcutaneous (SC) weekly during the 6-week MTX Run-in Period. Pegloticase 8 mg intravenous (IV) every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Pegloticase + MTX Treatment Period
Lost to Follow-up
|
3
|
|
Pegloticase + MTX Treatment Period
Withdrawal by Subject
|
3
|
Baseline Characteristics
Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy
Baseline characteristics by cohort
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Age, Continuous
|
58.6 years
STANDARD_DEVIATION 11.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Month 6Population: Intent-to-Treat (ITT) Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate.
An sUA responder is defined as a participant achieving and maintaining sUA \<6 mg/dL for at least 80% of the time during Month 6 (Weeks 20, 21, 22, 23 and 24).
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
|
9.1 percentage of participants
Interval 0.2 to 41.3
|
SECONDARY outcome
Timeframe: Month 3Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate.
An sUA responder is defined as a participant achieving and maintaining sUA \<6 mg/dL for at least 80% of the time during Month 3 (Weeks 10 to 14).
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Percentage of sUA Responders (sUA < 6 mg/dL) During Month 3
|
9.1 percentage of participants
Interval 0.2 to 41.3
|
SECONDARY outcome
Timeframe: Day1 to Week 24Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate.
Individual participant sUA discontinuation criteria are met when the lowest available interim sUA value after the pegloticase infusion at Week 2, 4, 6, 8, 10 or 12 is less than a 50% reduction from the highest sUA value measured between Screening and pre-infusion on Day 1.
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Percentage of Participants Who Experienced Any of the Following Events From Day 1 to Week 24: Infusion Reaction (IR) Leading to Discontinuation of Treatment, Anaphylaxis or Meeting Individual Participant sUA Discontinuation Criteria
|
81.8 percentage of participants
Interval 48.2 to 97.7
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate; participants with an assessment at given time point.
DECT scans measure urate deposition volume. DECT scans at Week 24 were taken for hands, foot/ankle, and knees.
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=9 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Mean Change From Baseline in Urate Deposition Volume Measured by Dual Energy Computed Tomography (DECT) to Week 24
Change in Total Urate Volume of Hands
|
-0.073 cm^3
Standard Deviation 0.1270
|
|
Mean Change From Baseline in Urate Deposition Volume Measured by Dual Energy Computed Tomography (DECT) to Week 24
Change in Total Urate Volume of Foot/Ankle
|
-1.540 cm^3
Standard Deviation 1.7545
|
|
Mean Change From Baseline in Urate Deposition Volume Measured by Dual Energy Computed Tomography (DECT) to Week 24
Change in Total Urate Volume of Knees
|
-1.207 cm^3
Standard Deviation 0.9073
|
SECONDARY outcome
Timeframe: Baseline, Week 14, Week 24Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate; participants with an assessment at given time point.
HAQ-DI is a self-report functional status instrument that is filled out by the participant and measures disability over the past week via 20 questions relating to 8 domains of function: dressing grooming, arising, eating, walking, hygiene, reach, grip, usual activities. For each of the categories, participants reported the amount of difficulty they had in performing 2 or 3 specific subcategory items. The standard disability score is calculated from the 8 categories by dividing the sum of the individual categories by the number of categories answered, yielding a score from 0 (without any difficulty) to 3 (unable to do), with higher values indicating higher disability.
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Mean Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Weeks 14 and 24
Change at Week 14
|
0.25 score on a scale
Standard Deviation 0.617
|
|
Mean Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Weeks 14 and 24
Change at Week 24
|
0.10 score on a scale
Standard Deviation 0.163
|
SECONDARY outcome
Timeframe: Baseline, Week 14, Week 24Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate; participants with an assessment at given time point.
The HAQ pain scale asks participants to record how much pain they have had in the past week on a scale of 0-100 where zero represents no pain and 100 represents severe pain.
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Score at Weeks 14 and 24
Change at Week 14
|
10.67 score on a scale
Standard Deviation 19.664
|
|
Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Score at Weeks 14 and 24
Change at Week 24
|
-4.00 score on a scale
Standard Deviation 15.166
|
SECONDARY outcome
Timeframe: Baseline, Week 14, Week 24Population: ITT Analysis Set: all participants who receive at least 1 dose of pegloticase + methotrexate; participants with an assessment at given time point.
The HAQ health scale is a measure of overall health. Participants are asked to rate how well they are doing on a scale of 0 to 100, where zero represents very well and 100 represents very poor health.
Outcome measures
| Measure |
Pegloticase Plus Methotrexate
n=11 Participants
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period. Pegloticase 8 mgIV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|
|
Mean Change From Baseline in HAQ Health Score at Weeks 14 and 24
Change at Week 14
|
8.00 score on a scale
Standard Deviation 45.343
|
|
Mean Change From Baseline in HAQ Health Score at Weeks 14 and 24
Change at Week 24
|
-11.40 score on a scale
Standard Deviation 24.389
|
Adverse Events
MTX Run-In Period
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Pegloticase + MTX Treatment Period
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MTX Run-In Period
n=13 participants at risk
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period.
|
Pegloticase + MTX Treatment Period
n=11 participants at risk
Pegloticase 8 mg IV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|---|
|
Infections and infestations
Perineal abscess
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Infections and infestations
Septic shock
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
Other adverse events
| Measure |
MTX Run-In Period
n=13 participants at risk
MTX 15 or 25 mg SC weekly during the 6-week MTX Run-in Period.
|
Pegloticase + MTX Treatment Period
n=11 participants at risk
Pegloticase 8 mg IV every 2 weeks and MTX 15 or 25 mg SC weekly for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Ear and labyrinth disorders
Vertigo
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Eye disorders
Cataract
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Eye disorders
Vision blurred
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
General disorders
Fatigue
|
15.4%
2/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
General disorders
Injection site bruising
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Injury, poisoning and procedural complications
Contusion
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
18.2%
2/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Investigations
Blood glucose increased
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Metabolism and nutrition disorders
Gout
|
46.2%
6/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
63.6%
7/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
18.2%
2/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
18.2%
2/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Nervous system disorders
Headache
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Nervous system disorders
Paraesthesia
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
9.1%
1/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Vascular disorders
Flushing
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
|
Vascular disorders
Hypertension
|
7.7%
1/13 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
0.00%
0/11 • From enrollment (all-cause mortality) or first dose of study drug (adverse events) up to Week 48 + 30 days (±3 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER