Chronic Gout
Conditions
Brief summary
This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Participants will be randomized 1:1 to receive treatment with SEL-212 or KRYSTEXXA® for 6 months. Efficacy assessments, as measured by serum uric acid (SUA) levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study.
Detailed description
This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Participants will be randomized 1:1 to receive treatment with SEL-212 \[a combination of pegadricase (SEL-037) and ImmTOR (SEL-110)\] or KRYSTEXXA® for 6 months. Study participants in the SEL-212 arm will receive study drug every 28 days for a total of up to 6 infusions of SEL-212. Study participants in the KRYSTEXXA® arm will receive study drug according to the manufacturer's prescribing information, i.e., every 14 days for a total of up to 12 infusions of KRYSTEXXA®. Efficacy assessments, as measured by SUA levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study.
Interventions
DRUGSEL-212
Administered as specified in the treatment arm
DRUGKRYSTEXXA®
Administered as specified in the treatment arm
Sponsors
Selecta Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Assessments of qualitative endpoints will be conducted on an assessor-blinded basis.
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. History of symptomatic gout defined as: 1. ≥ 3 gout flares within 18 months of Screening or 2. Presence of ≥ 1 tophus or 3. Current diagnosis of gouty arthritis 2. At the Screening Visit: male age 21 - 80 years, inclusive, or female of non-childbearing potential age 21-80 years, inclusive, where non-childbearing potential is defined as: 1. \> 6 weeks after hysterectomy with or without surgical bilateral salpingooperhectony or 2. Post-menopausal (\> 24 months of natural amenorrhea) 3. Has at the Screening Visit SUA ≥ 7 mg/dL, with chronic refractory gout defined as having failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the medically appropriate dose or for whom these drugs are contraindicated; 4. Willing to provide written informed consent prior to the conduct of any study specific procedures; 5. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits Key
Exclusion criteria
1. Prior exposure to any experimental or marketed uricase (e.g., pegloticase \[Krystexxa®\], pegadricase \[SEL-037\], rasburicase \[Elitek, Fasturtec\]); 2. History of anaphylaxis or severe allergic reactions to medications; 3. History of any allergy to pegylated products 4. Drugs known to interact with Rapamune cannot be used during the trial; 5. Uncontrolled diabetes; 6. Glucose-6-phosphate dehydrogenase (G6PD) deficiency; 7. Uncontrolled hypertension; 8. Participants whose arrhythmia is unstable on current treatment; 9. History of coronary artery disease, including myocardial infarction or unstable angina, within the last 6 months; 10. Congestive heart failure; 11. History of hematological disorders within 1 year or autoimmune disorders, is immunosuppressed or immunocompromised; 12. Has received an inactivated vaccine in the previous 3 months or has received a live virus vaccine in the previous 6 months; 13. Is planning to receive any vaccination or live virus vaccination during the study;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serum Uric Acid (SUA) Reduction of < 6 mg/dL for at Least 80% of the Time | Up to Month 6 | The average of the data collected during Month 3 and Month 6 was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SUA Reduction of < 6 mg/dL for 100% of the Time During Month 6 | Month 6 | — |
| Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Baseline to End of Month 3, Baseline to End of Month 6 | Eight categories were assessed by the HAQ-DI: 1) dressing and grooming, 2) arising, 3) eating, 4) walking, 5) hygiene, 6) reaching, 7) gripping, and 8) common daily activities. There were 2 or 3 questions for each category. Scoring within each category was on a 4-point Likert scale from 0 (without any difficulty) to 3 (unable to do). The score given to each section was the worst (highest) score within the section. The HAQ-DI total score was calculated if 6 or more sections were available. The average of the 8 category scores was reported as the HAQ-DI total score on a scale of 0 to 3. Reduction from baseline, and lower scores indicated better QoL. |
| QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Baseline to End of Month 3, Baseline to End of Month 6 | The PrGA was administered to assess the severity of the participant's disease on a scale from 0 (participant feels very well) to 100 (participant feels very poor). Reduction from baseline, and lower scores indicated less severe disease. |
| QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Baseline to End of Month 3, Baseline to End of Month 6 | The SF-36 is a 36-item questionnaire to assesses a participant's health status using 8 health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions. The mental component reports the average of all the emotionally relevant items and the physical component reports the average of all the physical relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 indicates no disability. Median change can range from -100 to 100. A positive median change indicated an improved outcome. |
| Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6 | Month 6 | — |
| Number of Gout Flares Per 3-Month Period | Month 1 to Month 3, Month 4 to Month 6 | — |
| Change From Baseline in Number of Tender Joints | Baseline to End of Month 6 | — |
| Change From Baseline in Number of Swollen Joints | Baseline to End of Month 6 | — |
| Number of Participants With Gout Flares Per 3-Month Period | Month 1 to Month 3, Month 4 to Month 6 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled across clinical sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| SEL-212 Participants received SEL-212 via IV infusion every 28 days for up to 6 months | 83 |
| KRYSTEXXA Participants received KRYSTEXXA® according to the manufacturer's prescribing information every 14 days for up to 6 months | 87 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | Other than Specified | 7 | 4 |
| Overall Study | Withdrawal by Subject | 9 | 8 |
Baseline characteristics
| Characteristic | KRYSTEXXA | Total | SEL-212 |
|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 10.43 | 52.3 years STANDARD_DEVIATION 10.92 | 52.6 years STANDARD_DEVIATION 11.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 36 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants | 134 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 32 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 69 Participants | 131 Participants | 62 Participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 85 Participants | 163 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 87 |
| other Total, other adverse events | 60 / 83 | 53 / 87 |
| serious Total, serious adverse events | 7 / 83 | 8 / 87 |
Outcome results
Primary
Number of Participants With Serum Uric Acid (SUA) Reduction of < 6 mg/dL for at Least 80% of the Time
The average of the data collected during Month 3 and Month 6 was reported.
Time frame: Up to Month 6
Population: ITT set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEL-212 | Number of Participants With Serum Uric Acid (SUA) Reduction of < 6 mg/dL for at Least 80% of the Time | 44 Participants |
| KRYSTEXXA | Number of Participants With Serum Uric Acid (SUA) Reduction of < 6 mg/dL for at Least 80% of the Time | 40 Participants |
p-value: 0.181Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Number of Swollen Joints
Time frame: Baseline to End of Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | Change From Baseline in Number of Swollen Joints | Baseline | 3.0 number of swollen joints | Standard Deviation 5.39 |
| SEL-212 | Change From Baseline in Number of Swollen Joints | Change at End of Month 6 | -1.6 number of swollen joints | Standard Deviation 5.51 |
| KRYSTEXXA | Change From Baseline in Number of Swollen Joints | Baseline | 3.7 number of swollen joints | Standard Deviation 6.64 |
| KRYSTEXXA | Change From Baseline in Number of Swollen Joints | Change at End of Month 6 | -1.9 number of swollen joints | Standard Deviation 8.38 |
Secondary
Change From Baseline in Number of Tender Joints
Time frame: Baseline to End of Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | Change From Baseline in Number of Tender Joints | Baseline | 5.2 number of tender joints | Standard Deviation 8.81 |
| SEL-212 | Change From Baseline in Number of Tender Joints | Change at End of Month 6 | -2.4 number of tender joints | Standard Deviation 8.98 |
| KRYSTEXXA | Change From Baseline in Number of Tender Joints | Baseline | 4.1 number of tender joints | Standard Deviation 7.49 |
| KRYSTEXXA | Change From Baseline in Number of Tender Joints | Change at End of Month 6 | -2.7 number of tender joints | Standard Deviation 6.93 |
Secondary
Number of Gout Flares Per 3-Month Period
Time frame: Month 1 to Month 3, Month 4 to Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | Number of Gout Flares Per 3-Month Period | Month 1 to Month 3 | 1.1 number of flares | Standard Deviation 1.16 |
| SEL-212 | Number of Gout Flares Per 3-Month Period | Mont 4 to Month 6 | 0.2 number of flares | Standard Deviation 0.56 |
| KRYSTEXXA | Number of Gout Flares Per 3-Month Period | Month 1 to Month 3 | 0.8 number of flares | Standard Deviation 1.24 |
| KRYSTEXXA | Number of Gout Flares Per 3-Month Period | Mont 4 to Month 6 | 0.3 number of flares | Standard Deviation 1.15 |
Secondary
Number of Participants With Gout Flares Per 3-Month Period
Time frame: Month 1 to Month 3, Month 4 to Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SEL-212 | Number of Participants With Gout Flares Per 3-Month Period | Month 1 to Month 3 | 50 Participants |
| SEL-212 | Number of Participants With Gout Flares Per 3-Month Period | Month 4 to Month 6 | 16 Participants |
| KRYSTEXXA | Number of Participants With Gout Flares Per 3-Month Period | Month 1 to Month 3 | 42 Participants |
| KRYSTEXXA | Number of Participants With Gout Flares Per 3-Month Period | Month 4 to Month 6 | 15 Participants |
Secondary
Number of Participants With SUA Reduction of < 6 mg/dL for 100% of the Time During Month 6
Time frame: Month 6
Population: ITT set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEL-212 | Number of Participants With SUA Reduction of < 6 mg/dL for 100% of the Time During Month 6 | 38 Participants |
| KRYSTEXXA | Number of Participants With SUA Reduction of < 6 mg/dL for 100% of the Time During Month 6 | 36 Participants |
Secondary
Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6
Time frame: Month 6
Population: ITT set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SEL-212 | Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6 | 45 Participants |
| KRYSTEXXA | Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6 | 41 Participants |
Secondary
QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale
The PrGA was administered to assess the severity of the participant's disease on a scale from 0 (participant feels very well) to 100 (participant feels very poor). Reduction from baseline, and lower scores indicated less severe disease.
Time frame: Baseline to End of Month 3, Baseline to End of Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Baseline | 42.8 score on a scale | Standard Deviation 26.65 |
| SEL-212 | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Change at End of Month 3 | -20.9 score on a scale | Standard Deviation 25.38 |
| SEL-212 | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Change at End of Month 6 | -24.6 score on a scale | Standard Deviation 24.87 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Baseline | 40.5 score on a scale | Standard Deviation 28.62 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Change at End of Month 3 | -15.8 score on a scale | Standard Deviation 32.97 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Provider Global Assessment of Disease Activity (PrGA) Scale | Change at End of Month 6 | -22.0 score on a scale | Standard Deviation 29.37 |
Secondary
QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale
The SF-36 is a 36-item questionnaire to assesses a participant's health status using 8 health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions. The mental component reports the average of all the emotionally relevant items and the physical component reports the average of all the physical relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 indicates no disability. Median change can range from -100 to 100. A positive median change indicated an improved outcome.
Time frame: Baseline to End of Month 3, Baseline to End of Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Physical Component Scores at Baseline | 43.822 score on a scale | Standard Deviation 10.9976 |
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Physical Component Scores at End of Month 3 | 3.323 score on a scale | Standard Deviation 9.9242 |
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Physical Component Scores at End of Month 6 | 5.881 score on a scale | Standard Deviation 9.0453 |
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Mental Component Scores at Baseline | 51.977 score on a scale | Standard Deviation 8.4731 |
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Mental Component Scores at End of Month 3 | 0.381 score on a scale | Standard Deviation 6.7469 |
| SEL-212 | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Mental Component Scores at End of Month 6 | 1.516 score on a scale | Standard Deviation 6.4824 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Mental Component Scores at End of Month 3 | 1.229 score on a scale | Standard Deviation 7.6445 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Physical Component Scores at Baseline | 43.345 score on a scale | Standard Deviation 11.2714 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Mental Component Scores at Baseline | 53.386 score on a scale | Standard Deviation 9.3171 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Physical Component Scores at End of Month 3 | 5.768 score on a scale | Standard Deviation 9.0712 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Mental Component Scores at End of Month 6 | -0.322 score on a scale | Standard Deviation 8.0626 |
| KRYSTEXXA | QoL as Assessed by Change From Baseline in Short Form Health Survey 36 (SF-36) Scale | Change in Physical Component Scores at End of Month 6 | 7.448 score on a scale | Standard Deviation 8.3909 |
Secondary
Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale
Eight categories were assessed by the HAQ-DI: 1) dressing and grooming, 2) arising, 3) eating, 4) walking, 5) hygiene, 6) reaching, 7) gripping, and 8) common daily activities. There were 2 or 3 questions for each category. Scoring within each category was on a 4-point Likert scale from 0 (without any difficulty) to 3 (unable to do). The score given to each section was the worst (highest) score within the section. The HAQ-DI total score was calculated if 6 or more sections were available. The average of the 8 category scores was reported as the HAQ-DI total score on a scale of 0 to 3. Reduction from baseline, and lower scores indicated better QoL.
Time frame: Baseline to End of Month 3, Baseline to End of Month 6
Population: ITT set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SEL-212 | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Baseline | 0.78 score on a scale | Standard Deviation 0.774 |
| SEL-212 | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Change at End of Month 3 | -0.14 score on a scale | Standard Deviation 0.725 |
| SEL-212 | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Change at End of Month 6 | 0.04 score on a scale | Standard Deviation 0.723 |
| KRYSTEXXA | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Baseline | 0.79 score on a scale | Standard Deviation 0.834 |
| KRYSTEXXA | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Change at End of Month 3 | -0.10 score on a scale | Standard Deviation 0.795 |
| KRYSTEXXA | Quality of Life (QoL) as Assessed by Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Scale | Change at End of Month 6 | -0.12 score on a scale | Standard Deviation 0.739 |