A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy

This is one of two replicate randomized, double-blind, placebo-controlled, parallel arm trials to determine the safety and efficacy of two different dose levels of SEL-212 compared to placebo. 112 and 153 patients, stratified as to the presence or absence of tophi, were randomized in a 1:1:1 allocation ratio prior to Baseline to receive treatment with one of two dose levels of SEL-212 or placebo every 28 days for approximately 6 months in each trial respectively (SEL-212/301 and SEL-212/302). The SEL-212 doses differed as to the SEL-110.36 component. Participants received SEL-037 administered at a dose of 0.2 mg/kg via intravenous (IV) infusion immediately after receiving SEL-110.36 at a dose of either 0.1 mg/kg (SEL-212 low-dose) or 0.15 mg/kg (SEL-212 high-dose) via IV infusion. The placebo consisted of normal saline.

Upon completion of the 6-month double-blinded, placebo-controlled portion of the study, SEL-212/301 continued in a blinded, placebo-controlled 6-month extension. This provided up to 12 months of continuous treatment with SEL-212 in a placebo controlled fashion.

Efficacy assessments were conducted at intervals that are appropriate to determine treatment effect with samples for the primary endpoint drawn during Treatment Period 6. Safety was monitored throughout the study with an independent data safety monitoring board (DSMB).

Primary Outcome Measures

1. Proportion of Participants Who Achieved and Maintained Reduction in Serum Uric Acid (sUA) < 6 Milligrams Per Deciliter (mg/dL) for At Least 80% of The Time During Treatment Period 6 (Month 6)

Secondary Outcome Measures

1. Change From Baseline in Mean sUA
2. Percentage Change From Baseline in Mean sUA
3. Change From Baseline in the Physical Component Summary Score of the Short Form Health Survey (SF-36)
   The SF-36 is a 36-item scale constructed to survey health status and quality of life (QoL). The SF-36 assesses 8 health concepts, which are the weighted sums of the questions in their section: 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. Each scale was directly transformed into a 0-100 scale, and the total average scores were calculated across the 8 health concepts. The 8 domains contributed to physical component summary and mental component summary scores. Total scores for the physical component summary score ranged from 0-100, with a higher score indicating better health outcomes.
4. Proportion of Participants With at Least Partial Response (PR) (as Best Response) in Overall Tophus Response Evaluation in Participants With Tophi at Baseline
   Baseline photographs of the hands and feet of each participant were obtained using a standardized method in all participants together with photographs of up to 2 other representative sites of tophaceous disease. The baseline photographs were assessed by three independent reviewers to prospectively identify sites of tophaceous disease present at the start of treatment. Up to 5 tophi in the photographs were chosen by the reviewers for measurement over the course of therapy. The reviewers assessed the photographs for size of each target tophus using image analysis software. At least PR was defined as at least a 50% decrease in the area of at least one tophus, and includes participants with complete response (CR). Data are presented for the proportion of participants with at least PR (as best response).
5. Proportion of Participants Who Achieved and Maintained Reduction of sUA < 6 mg/dL for at Least 80% of the Time During Month 6 in the Subset of Participants With Tophi at Baseline
   The number of responders in the subgroup of Intent-to-Treat participants with tophi at baseline divided by the number of Intent-to-Treat participants with tophi at baseline.
6. Change From Baseline to Month 6 in Number of Tender Joints
   Tender and/or swollen joints were counted. The following joints were assessed: metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the hands; the metatarsophalangeal and interphalangeal joints of the feet; shoulder, elbow, wrist, knee, ankle, tarsus, sternoclavicular, and acromioclavicular joints.
7. Change From Baseline to Month 6 in the Total Score of the Health Assessment Questionnaire Disability Index (HAQ-DI)
   The HAQ-DI assesses fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both the upper and lower extremities. It includes 20 items in 8 categories: &quot;activity&quot;, &quot;arising&quot;, &quot;dressing and grooming&quot;, &quot;eating&quot;, &quot;grip&quot;, &quot;hygiene&quot;, &quot;reach&quot; and &quot;walking&quot;. Scoring within each section was on a 4-point Likert scale from 0 (without any difficulty) to 3 (unable to do), with higher score showing more disability. The average of the 8 category scores was reported as the HAQ-DI total score on a scale of 0 to 3. A decrease in HAQ-DI score from baseline indicated an improvement in the participant&#039;s condition.
8. Incidence of Gout Flare During Treatment Periods 1-6 (Months 1-6)
   Gout flare was assessed as part of adverse event (AE) collection. Gout flares were assessed during the Treatment Phase using a validated definition of flares in participants with established gout. A gout flare (per Gaffo et al. 2018) was defined as the fulfillment of at least 3 of the following 4 criteria: 1. Participant-defined gout flare, 2. Pain at rest score of \&gt;3 on a 0-10-point numerical rating scale, 3. Presence of at least 1 swollen joint, 4. Presence of at least 1 warm joint. Data are presented for the LS mean incidence per month of gout flares during Treatment Periods 1-6 (Months 1-6). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the &#039;Reported Adverse Events&#039; Section.
9. Incidence of Gout Flare During Treatment Periods 1-3 (Months 1-3)
   Gout flare was assessed as part of adverse event (AE) collection. Gout flares were assessed during the Treatment Phase using a validated definition of flares in participants with established gout. A gout flare (per Gaffo et al. 2018) was defined as the fulfillment of at least 3 of the following 4 criteria: 1. Participant-defined gout flare, 2. Pain at rest score of \&gt;3 on a 0-10-point numerical rating scale, 3. Presence of at least 1 swollen joint, 4. Presence of at least 1 warm joint. Data are presented for the LS mean incidence per month of gout flares during Treatment Periods 1-3 (Months 1-3). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the &#039;Reported Adverse Events&#039; Section.