Multi-Dose Safety/Pharmacodynamic Study of SEL-212/SEL-037 in Subjects With Symptomatic Gout & Elevated Blood Uric Acid

Study Overview
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Brief Summary
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This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase (SEL-037) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in subjects with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses ( 5 monthly IV infusions) of pegsiticase (SEL-037) alone. Participants will be monitored for safety endpoints through the 5th treatment cycle plus 30 days .Pharmacokinetic samples will be drawn at pre-determined time points in addition to weekly serum uric acid levels.

Detailed Description
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This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase ( SEL-037, also known as pegadricase) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in participants with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses (5 monthly IV infusions) of pegsiticase (SEL-037) alone. Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming. All participants will be monitored for safety and tolerability to drug throughout the study on a weekly schedule. Pharmacokinetic and pharmacodynamic parameters will at specific timepoints to monitor for continued efficacy. Pharmacodynamic parameters measured include uric acid levels and levels of ADAs. The study duration per enrolled participant will be approximately 6 months including a 1 month screening period followed by 5 treatment cycles and an end of treatment visit which will occur 30 days after the last IV infusion .

Official Title
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An Open Label Phase II Multiple Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 Followed by Open Label Administration of SEL-037 in Subjects With Symptomatic Gout and Elevated Blood Uric Acid

Conditions
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Gout Chronic, Hyperuricemia

Intervention / Treatment
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* Drug: SEL-212
* Drug: SEL-037
* Drug: SVP-rapamycin (SEL-110)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (age 21-75 inclusive) men and women of non child bearing potential with established or symptomatic gout which is defined as having at least ONE of any of the 3 following factors: ≥ 1 tophus 1 gout flare within the last 6 months Chronic gouty arthropathy Screening serum uric acid of >6 mg/dL On a gout flare prophylactic regimen for 7 days prior to first dose Willing to provide written informed consent prior to first study procedure is performed. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits. Exclusion Criteria: History of anaphylaxis or severe allergic reaction. History of an allergy to pegylated products. Women of child bearing potential, Defined as: <6 weeks after surgical bilateral salpingooperhectony with or without hysterectomy Pre or perimenopausal ( < less than 24 months of natural amenorrhea) Initiation or change in dose of hormone-replacement therapy for menopausal women less than 1 month prior to the Screening Visit or during the Screening Phase would be exclusionary. If after being on a stable dose of hormone-replacement therapy for one month the patient may be considered for the study if she continues to meet all other inclusion and exclusion criteria Uncontrolled diabetes with baseline HbA1c ≥8%; Glucose-6-phosphate dehydrogenase deficiency; Uncontrolled hypertension Ongoing treatment for arrhythmia, including placement of an implantable defibrillator; History of coronary artery disease, including myocardial infarction; Congestive heart failure, New York Heart Association Class III or IV; ECG with evidence of prior myocardial infarction, clinically significant arrhythmia, or other abnormalities that, in the opinion of the investigator, are consistent with significant underlying cardiac disease; History of hematological or autoimmune disorders, is immunosuppressed or immunocompromised; Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®), pegsiticase (SEL-037) History of malignancy within the last 5 years other than basal skin cancer; Subjects who, in the opinion of the investigator, present with a condition that would compromise their safety or that would make study completion unlikely.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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-037 Pegadricase LD (low dose) alone<br>Pegadricase 0.2 mg/kg intravenous (IV) every 28 days for 5 treatments | Drug: SEL-037<br>* SEL-037, biologic<br>* Other names: Pegadricase;|
| Experimental: SEL-037 Pegadricase HD (high dose) alone<br>Pegadricase 0.4 mg/kg intravenous (IV) every 28 days for 5 treatments | Drug: SEL-037<br>* SEL-037, biologic<br>* Other names: Pegadricase;|
| Experimental: SEL-212, Pegadricase LD & SEL-110 (1a)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.05 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (1b)<br>Pegadricase 0.4 mg/kg IV plus SEL-110 0.05 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase LD & SEL-110 (2a)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.08 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (2b)<br>Pegadricase 0.4 mg/kg IV plus SEL-110 0.08 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (3a)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (3b)<br>Pegadricase 0.4 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (4a)<br>Pegadricase 0.4 mg/kg IV plus SEL-110 0.125 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (4b)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.2 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (5a)<br>Pegadricase 0.4 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 3 treatments, followed by pegadricase 0.4 mg/kg IV every 28 days for 2 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (5b)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 5 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (6a)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.10 mg/kg IV every 28 days for 1 treatment followed by pegadricase 0.2 mg/kg IV plus SEL-110 0.15 mg/kg IV every 28 days for 4 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|
| Experimental: SEL-212, Pegadricase HD & SEL-110 (6b)<br>Pegadricase 0.2 mg/kg IV plus SEL-110 0.1 mg/kg IV every 28 days for 5 treatments | Drug: SEL-212<br>* SEL-212, biologic<br>* Other names: Pegadricase plus SVP-rapamycin;Drug: SVP-rapamycin (SEL-110)<br>* SVP-rapamycin, biologic<br>* Other names: SEL-110;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Multiple Intravenous Infusions of SEL-037 or SEL-212 as Assessed by the Percentage of Participants Experiencing Serious Adverse Events and Those Adverse Events Reported by 5 Percentage or More in the Safety Analysis Set | To determine the safety and tolerability of SEL-037 (pegadricase) after up to 5 monthly infusions, of SEL-212 for 3 monthly infusions followed by 2 monthly infusions of SEL-037 (pegadricase), or of SEL-212 for 5 monthly infusions as assessed by the percentage of participants in a treatment arm experiencing serious adverse events and percentage of participants experiencing those adverse events that were reported by 5 or more percentage of participants in any arm in the safety analysis set | Five monthly infusions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Reduced Serum Uric Acid After Multiple Monthly IV Infusions With or Without SEL-110 | Measurement of the number of participants with reduced serum uric acid after multiple monthly infusions with or without SEL-110 as determined by values of sUA < 6 mg/dL at the end of Treatment Period 3 and at the end of Treatment Period 5 in eligible subjects | 3 and 5 months |