A Study to Compare the Efficacy of SEL-212 to KRYSTEXXA® in Gout Participants Refractory to Conventional Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Study to Compare the Efficacy of SEL-212 to KRYSTEXXA® in Gout Patients Refractory to Conventional Therapy

Conditions
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Chronic Gout

Intervention / Treatment
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* Drug: SEL-212
* Drug: KRYSTEXXA®


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: History of symptomatic gout defined as: ≥ 3 gout flares within 18 months of Screening or Presence of ≥ 1 tophus or Current diagnosis of gouty arthritis 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: > 6 weeks after hysterectomy with or without surgical bilateral salpingooperhectony or Post-menopausal (> 24 months of natural amenorrhea) 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; Willing to provide written informed consent prior to the conduct of any study specific procedures; Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits Key Exclusion Criteria: Prior exposure to any experimental or marketed uricase (e.g., pegloticase [Krystexxa®], pegadricase [SEL-037], rasburicase [Elitek, Fasturtec]); History of anaphylaxis or severe allergic reactions to medications; History of any allergy to pegylated products Drugs known to interact with Rapamune cannot be used during the trial; Uncontrolled diabetes; Glucose-6-phosphate dehydrogenase (G6PD) deficiency; Uncontrolled hypertension; Participants whose arrhythmia is unstable on current treatment; History of coronary artery disease, including myocardial infarction or unstable angina, within the last 6 months; Congestive heart failure; History of hematological disorders within 1 year or autoimmune disorders, is immunosuppressed or immunocompromised; Has received an inactivated vaccine in the previous 3 months or has received a live virus vaccine in the previous 6 months; Is planning to receive any vaccination or live virus vaccination during the study;

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEL-212<br>Intravenous (IV) infusion of SEL-212 every 28 days for up to 6 infusions | Drug: SEL-212<br>* Administered as specified in the treatment arm<br>|
| Active Comparator: KRYSTEXXA<br>IV infusion of KRYSTEXXA® according to the manufacturer's prescribing information every 14 days for up to 12 infusions | Drug: KRYSTEXXA®<br>* Administered as specified in the treatment arm<br>* Other names: Pegloticase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6 |  | Month 6 | 
| 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 | 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. | Baseline to End of Month 3, Baseline to End of Month 6 | 
| 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. | Baseline to End of Month 3, Baseline to End of Month 6 | 
| 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. | Baseline to End of Month 3, 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 | 
| 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 |