Trial Outcomes & Findings for Observational Study of the Use of Pegloticase (KRYSTEXXA®) in Refractory Chronic Gout (NCT NCT01466166)
NCT ID: NCT01466166
Last Updated: 2019-01-11
Results Overview
Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.
Recruitment status
COMPLETED
Target enrollment
188 participants
Primary outcome timeframe
52 weeks
Results posted on
2019-01-11
Participant Flow
A total of 249 patients were screened at 66 of 112 activated clinical sites in the United States; 61 (24.5%) of the 249 patients were screen failures and 188 were enrolled.
Participant milestones
| Measure |
Pegloticase
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Overall Study
STARTED
|
188
|
|
Overall Study
Received Treatment
|
188
|
|
Overall Study
Completed 24 Weeks of Treatment
|
55
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
163
|
Reasons for withdrawal
| Measure |
Pegloticase
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Overall Study
Death
|
1
|
|
Overall Study
Lost to Follow-up
|
7
|
|
Overall Study
Infusion Reaction (IR)
|
27
|
|
Overall Study
Adverse Event (Other than IR)
|
11
|
|
Overall Study
Elevated Serum Uric Acid
|
78
|
|
Overall Study
Withdrawal by Subject
|
13
|
|
Overall Study
Sponsor Decision
|
4
|
|
Overall Study
Protocol Violation/Noncompliance
|
2
|
|
Overall Study
Other
|
20
|
Baseline Characteristics
Participants with available data
Baseline characteristics by cohort
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Age, Continuous
|
55.32 years
STANDARD_DEVIATION 13.15 • n=188 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=188 Participants
|
|
Sex: Female, Male
Male
|
169 Participants
n=188 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=188 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
168 Participants
n=188 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
White
|
131 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
Asian
|
16 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
30 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
1 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
2 Participants
n=188 Participants
|
|
Race/Ethnicity, Customized
Other
|
8 Participants
n=188 Participants
|
|
Baseline Serum Uric Acid
|
9.03 mg/dL
STANDARD_DEVIATION 2.29 • n=185 Participants • Participants with available data
|
|
Duration Since Initial Gout Diagnosis
|
15.54 years
STANDARD_DEVIATION 10.36 • n=188 Participants
|
|
Number of Gout Flares in Last 6 Months
|
7.60 flares
STANDARD_DEVIATION 12.17 • n=188 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: The intent-to-treat population included all enrolled participants
Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Participants With Infusion Reactions
|
42 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: All enrolled participants
Anaphylaxis was defined using the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria: Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula), and at least 1 of the following: 1. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). 2. Reduced blood pressure (i.e., systolic blood pressure \< 90 mm Hg or greater than 30% decrease from that patient's baseline) or associated symptoms of end-organ failure (e.g., hypotonia \[collapse\], syncope, incontinence).
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Participants With Anaphylaxis
|
5 Participants
|
PRIMARY outcome
Timeframe: From first dose of study drug to the end of the 12-week follow-up period (63 weeks).Population: All enrolled participants
Immune complex-related events were defined as any presumptive immune complex-related disorders that were confirmed by an appropriate investigation of the event and of complement markers (C3 and C4 levels). Clinical manifestations could have included skin rash, arthralgia, arthritis, proteinuria, serum sickness, and cryoglobulinemia.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Participants With Immune Complex-related Events
|
3 Participants
|
SECONDARY outcome
Timeframe: Week 24 and week 52Population: Participants with missing values at week 24 or 52 are counted as not achieving normalization
Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52
Week 24
|
27.7 percentage of participants
|
|
Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52
Week 52
|
12.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, week 24 and week 48Population: Enrolled participants with a value at baseline and each time point
The number of gout flares occurring in the 2 weeks prior to each visit. Baseline number of flares was calculated as the average number of flares that occurred in the 6-month baseline period divided by 12 weeks.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Change From Baseline in Number of Gout Flares
Week 24
|
-0.83 flares
Standard Deviation 0.88
|
|
Change From Baseline in Number of Gout Flares
Week 48
|
-1.00 flares
Standard Deviation 0.89
|
SECONDARY outcome
Timeframe: Baseline and weeks 24 and 52Population: Enrolled participants with available data at baseline and each time point.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Swollen Joints Over Time
Baseline
|
8.60 swollen joints
Standard Deviation 10.847
|
|
Number of Swollen Joints Over Time
Week 24
|
4.05 swollen joints
Standard Deviation 7.241
|
|
Number of Swollen Joints Over Time
Week 52
|
1.46 swollen joints
Standard Deviation 3.336
|
SECONDARY outcome
Timeframe: Baseline and weeks 24 and 52Population: Enrolled participants with available data at baseline and each time point.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Tender Joints Over Time
Baseline
|
9.33 tender joints
Standard Deviation 11.715
|
|
Number of Tender Joints Over Time
Week 24
|
2.38 tender joints
Standard Deviation 5.539
|
|
Number of Tender Joints Over Time
Week 52
|
0.79 tender joints
Standard Deviation 1.318
|
SECONDARY outcome
Timeframe: Baseline and weeks 24 and 52Population: Enrolled participants with available data at baseline and each time point.
Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.
Outcome measures
| Measure |
Pegloticase
n=188 Participants
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Number of Palpable Tophi Over Time
Baseline
|
13.58 tophi
Standard Deviation 18.999
|
|
Number of Palpable Tophi Over Time
Week 24
|
5.70 tophi
Standard Deviation 5.643
|
|
Number of Palpable Tophi Over Time
Week 52
|
3.68 tophi
Standard Deviation 3.038
|
Adverse Events
Pegloticase
Serious events: 31 serious events
Other events: 130 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Pegloticase
n=188 participants at risk
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Cardiac disorders
Atrial fibrillation
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Cardiac disorders
Cardiac failure
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Cardiac disorders
Cardiac failure congestive
|
1.1%
2/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Cardiac disorders
Coronary artery disease
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Congenital, familial and genetic disorders
Gastrointestinal arteriovenous malformation
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Gastrointestinal disorders
Pancreatitis
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Immune system disorders
Anaphylaxis
|
2.7%
5/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Immune system disorders
Drug hypersensitivity
|
1.6%
3/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Infections and infestations
Cellulitis
|
1.1%
2/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Infections and infestations
Pneumonia
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Infections and infestations
Septic shock
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Infections and infestations
Urinary tract infection
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Metabolism and nutrition disorders
Gout
|
1.1%
2/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Nervous system disorders
Transient ischaemic attack
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Psychiatric disorders
Mental status changes
|
1.1%
2/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Renal and urinary disorders
Renal failure
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Renal and urinary disorders
Renal failure acute
|
2.1%
4/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.1%
2/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Skin and subcutaneous tissue disorders
Subcutaneous emphysema
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Vascular disorders
Hypertension
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Vascular disorders
Hypotension
|
0.53%
1/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
Other adverse events
| Measure |
Pegloticase
n=188 participants at risk
Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
|
|---|---|
|
Immune system disorders
Drug hypersensitivity
|
5.9%
11/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
|
Metabolism and nutrition disorders
Gout
|
67.0%
126/188 • From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
|
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