Refractory Chronic Gout
Conditions
Brief summary
The primary purpose of this study is to observe patients being treated with pegloticase in a standard healthcare setting in order to evaluate the frequency and severity of infusion reactions, anaphylaxis and immune complex related events. Additionally, serious adverse events associated with pegloticase therapy will be identified.
Detailed description
This was a Phase 4, multicenter, open-label, single-arm observational study of pegloticase 8 mg administered intravenously every 2 weeks in adult hyperuricemic patients with gout refractory to conventional therapy. Study duration is approximately 63 weeks, including 51 weeks of treatment and 12 weeks of follow-up. The design of this study follows the FDA-approved Full Prescribing Information for the use of pegloticase and allows for capturing additional data related to the safety and efficacy of pegloticase within the standard healthcare setting.
Interventions
BIOLOGICALPegloticase
Pegloticase 8 mg intravenous every 2 weeks
Sponsors
Horizon Pharma Rheumatology LLC
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (age 18 years or more) with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated. * Patients who have made the decision, along with their treating physician, to begin treatment with KRYSTEXXA. * Patients who are willing and able to give informed consent and adhere to visit/protocol schedules.
Exclusion criteria
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency * Non-compensated congestive heart failure * Pregnancy or breast feeding * Prior treatment with pegloticase or another recombinant uricase * Known allergy to urate oxidase * Prior treatment or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug * Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Infusion Reactions | 52 weeks | 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. |
| Number of Participants With Anaphylaxis | 52 weeks | 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). |
| Number of Participants With Immune Complex-related Events | From first dose of study drug to the end of the 12-week follow-up period (63 weeks). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Tender Joints Over Time | Baseline and weeks 24 and 52 | — |
| Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 | Week 24 and week 52 | Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL. |
| Number of Palpable Tophi Over Time | Baseline and weeks 24 and 52 | Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs. |
| Change From Baseline in Number of Gout Flares | Baseline, week 24 and week 48 | 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. |
| Number of Swollen Joints Over Time | Baseline and weeks 24 and 52 | — |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Pegloticase Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician. | 188 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event (Other than IR) | 11 |
| Overall Study | Death | 1 |
| Overall Study | Elevated Serum Uric Acid | 78 |
| Overall Study | Infusion Reaction (IR) | 27 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Other | 20 |
| Overall Study | Protocol Violation/Noncompliance | 2 |
| Overall Study | Sponsor Decision | 4 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Pegloticase |
|---|---|
| Age, Continuous | 55.32 years STANDARD_DEVIATION 13.15 |
| Baseline Serum Uric Acid | 9.03 mg/dL STANDARD_DEVIATION 2.29 |
| Duration Since Initial Gout Diagnosis | 15.54 years STANDARD_DEVIATION 10.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 168 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Gout Flares in Last 6 Months | 7.60 flares STANDARD_DEVIATION 12.17 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 30 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants |
| Race/Ethnicity, Customized White | 131 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 188 |
| other Total, other adverse events | 130 / 188 |
| serious Total, serious adverse events | 31 / 188 |
Outcome results
Primary
Number of Participants With Anaphylaxis
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).
Time frame: 52 weeks
Population: All enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegloticase | Number of Participants With Anaphylaxis | 5 Participants |
Primary
Number of Participants With Immune Complex-related Events
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.
Time frame: From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
Population: All enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegloticase | Number of Participants With Immune Complex-related Events | 3 Participants |
Primary
Number of Participants With Infusion Reactions
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.
Time frame: 52 weeks
Population: The intent-to-treat population included all enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pegloticase | Number of Participants With Infusion Reactions | 42 Participants |
Secondary
Change From Baseline in Number of Gout Flares
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.
Time frame: Baseline, week 24 and week 48
Population: Enrolled participants with a value at baseline and each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegloticase | Change From Baseline in Number of Gout Flares | Week 24 | -0.83 flares | Standard Deviation 0.88 |
| Pegloticase | Change From Baseline in Number of Gout Flares | Week 48 | -1.00 flares | Standard Deviation 0.89 |
Secondary
Number of Palpable Tophi Over Time
Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.
Time frame: Baseline and weeks 24 and 52
Population: Enrolled participants with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegloticase | Number of Palpable Tophi Over Time | Baseline | 13.58 tophi | Standard Deviation 18.999 |
| Pegloticase | Number of Palpable Tophi Over Time | Week 24 | 5.70 tophi | Standard Deviation 5.643 |
| Pegloticase | Number of Palpable Tophi Over Time | Week 52 | 3.68 tophi | Standard Deviation 3.038 |
Secondary
Number of Swollen Joints Over Time
Time frame: Baseline and weeks 24 and 52
Population: Enrolled participants with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegloticase | Number of Swollen Joints Over Time | Baseline | 8.60 swollen joints | Standard Deviation 10.847 |
| Pegloticase | Number of Swollen Joints Over Time | Week 24 | 4.05 swollen joints | Standard Deviation 7.241 |
| Pegloticase | Number of Swollen Joints Over Time | Week 52 | 1.46 swollen joints | Standard Deviation 3.336 |
Secondary
Number of Tender Joints Over Time
Time frame: Baseline and weeks 24 and 52
Population: Enrolled participants with available data at baseline and each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pegloticase | Number of Tender Joints Over Time | Baseline | 9.33 tender joints | Standard Deviation 11.715 |
| Pegloticase | Number of Tender Joints Over Time | Week 24 | 2.38 tender joints | Standard Deviation 5.539 |
| Pegloticase | Number of Tender Joints Over Time | Week 52 | 0.79 tender joints | Standard Deviation 1.318 |
Secondary
Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52
Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.
Time frame: Week 24 and week 52
Population: Participants with missing values at week 24 or 52 are counted as not achieving normalization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegloticase | Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 | Week 24 | 27.7 percentage of participants |
| Pegloticase | Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 | Week 52 | 12.2 percentage of participants |