Study Description

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 hig-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.

Placebo subjects who completed both phases of the study will be offered enrollment in an open-label extension study for treatment with SEL-212 (SEL-212/303).

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).

Condition or Disease	Intervention/Treatment
Chronic Gout	Drug: SEL-212 low-dose Drug: SEL-212 high-dose Other: Normal Saline

Study Design

Study Type	Interventional
Actual Enrollment	112 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	A Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy
Study Start Date	August 18, 2020
Actual Primary Completion Date	July 21, 2022
Actual Study Completion Date	December 1, 2022

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
SEL-212 low-dose SEL-212 low-dose Drug: SEL-037 (0.2 mg/kg) SEL-037, PEGylated uric acid specific enzyme (uricase) Other Names: Pegadricase, pegsiticase Drug: SEL-110.36 (0.1 mg/kg) SEL-110.36, ImmTOR	Drug: SEL-212 low-dose IV infusion of SEL-212 low-dose every 28 days for a total of up to 12 infusions
SEL-212 high-dose SEL-212 high-dose Drug: SEL-037 (0.2 mg/kg) SEL-037, PEGylated uric acid specific enzyme (uricase) Other Names: Pegadricase, pegsiticase Drug: SEL-110.36 (0.15 mg/kg) SEL-110.36, ImmTOR	Drug: SEL-212 high-dose
Placebo Normal saline	Other: Normal Saline

Outcome Measures

Primary Outcome Measures

1. Serum uric acid control during month 6 [6 months]
   The percentage of patients who achieve and maintain reduction in serum uric acid (sUA) < 6 mg/dL for at least 80% of the time during month 6 in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

Secondary Outcome Measures

1. Reduction of mean serum uric acid [6 months]
   To assess changes in mean serum uric acid in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
2. Percent reduction of mean serum uric acid [6 months]
   To assess percent changes in mean serum uric acid in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
3. SF-36 [6 months]
   To assess change in Patient Reported Outcomes (PROs) including assessments of: patients' quality of life (QoL) (SF-36) in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
4. Tophus burden [6 months]
   To assess change in tophus burden by photographic area assessment in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
5. Serum uric acid control in patients with tophi [6 months]
   To assess change in the percentage of patients with tophi at baseline who achieve and maintain reduction in serum uric acid (sUA) < 6 mg/dL for at least 80% of the time during month 6 in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
6. Tender and Swollen Joint Counts [6 months]
   To assess changes in number of tender and swollen joints in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
7. HAQ-DI [6 months]
   To assess change in Patient Reported Outcomes (PROs) including assessments of: activity limitation (HAQ-DI) in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo
8. Gout Flare Incidence [6 months]
   To assess changes in gout flare incidence in patients with gout refractory to conventional treatment treated with two different dose levels of SEL-212 compared to placebo

Eligibility Criteria

Ages Eligible for Study	19 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Has negative results of an FDA Emergency Use Authorized COVID-19 molecular assay for detection of SARS-CoV-2 RNA from a nasal or oropharyngeal specimen; History of symptomatic gout defined as: ≥ 3 gout flares within 18 months of Screening or Presence of ≥ 1 gout 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 nonchildbearing potential is defined as: a. > 6 weeks after hysterectomy with or without surgical bilateral salpingooperhectony or b. Post-menopausal (> 24 months of natural amenorrhea or in the absence of >24 months of amenorrhea, one documented confirmatory FSH measurement) Has chronic refractory gout defined as having failed to normalize sUA and whose signs and symptoms are inadequately controlled with any of the xanthine oxidase inhibitors, or for whom these drugs are contraindicated for the patient; Has at the Screening Visit SUA ≥ 7 mg/dL Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative antibodies to hepatitis C;
Exclusion Criteria	Has a history of anaphylaxis, severe allergic reactions, or severe atopy; Has a history of any allergy to pegylated products, including, but not limited to pegloticase (Krystexxa®), peginterferon alfa-2a (Pegasys®), peginterferon alfa-2b (PegIntron®), pegfilgrastim (Neulasta®), pegaptanib (Macugen®), pegaspargase (Oncaspar®), pegademase (Adagen®), peg-epoetin beta (Mircera®), pegvisomant (Somavert®) certolizumab pegol (Cimzia®), naloxegol (Movantik®), peginesatide (Omontys®), and doxorubicin liposome (Doxil®); Is taking and cannot discontinue known major CYP3A4/P-gp inhibitors or major CYP3A4/P-gp inducers at least 14 days before dosing. Patients must remain off these medications for the duration of the study, including natural products such as St. John's Wort or grapefruit juice. Is taking drugs known to interact with rapamycin (sirolimus - Rapamune®) such as cyclosporine, diltiazem, erythromycin, ketoconazole, posaconazole, voriconazole, itraconazole, rifampin, verapamil unless they are stopped 14 days prior to dosing and will not be used/prescribed during the trial. Had major surgery within 3 months of initial screening. Had a gout flare during Screening that was resolved for less than 1 week prior to first treatment with study drug (exclusive of chronic synovitis/arthritis) unless the patient has a history of inter-flare intervals of < 1 week. Has uncontrolled diabetes at Screening with HbA1c ≥ 8.5%; Has fasting Screening glucose > 240 mg/dL; Has fasting Screening triglyceride > 500 mg/dL; Has fasting Screening low-density lipoprotein (LDL) > 200 mg/dL; Has glucose-6-phosphate dehydrogenase (G6PD) deficiency; Has uncontrolled hypertension defined as blood pressure > 170/100 mmHg at Screening and 1 week prior to dosing Individual laboratory values which are exclusionary White blood cell count (WBC) < 3.0 x109/L Serum aspartate aminotransferase (AST) or alanine amino transferase (ALT) > 3x upper limit of normal (ULN) in the absence of known active liver disease Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 Urine albumin creatinine ratio (UACR) > 30 mg/g Hemoglobin (Hgb) < 9 g/dL Serum phosphate < 2.0 mg/dL Is receiving ongoing treatment for arrhythmia, including placement of an implantable defibrillator, unless considered stable and on active treatment; Has evidence of unstable cardiovascular disease or unstable cerebrovascular vascular disease. This includes patients who have had a cardiac/vascular event(s) in the last 3 months including heart attack, stroke or vascular bypass surgery or patients who are deemed, by their physician or PI, to have active cardiovascular, cerebrovascular or peripheral vascular symptoms/disease inadequately controlled by medication; Has congestive heart failure, New York Heart Association Class III or IV; Unless clinically stable and/or appropriately treated, electrocardiogram (ECG) with evidence of clinically significant arrhythmia or other abnormalities that, in the opinion of the investigator, are consistent with significant underlying cardiac disease; History of significant hematological disorders within 5 years or autoimmune disorders, and/or patient is currently immunosuppressed or immunocompromised; Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®®), pegadricase (SEL 037)) Patient has received a live vaccine in the previous 6 months. Patient is planning to receive any live vaccine during the study. History of malignancy within the last 5 years other than basal skin cancer; Patients with a documented history of moderate or severe alcohol or substance use disorder within the 12 months prior to randomization. History of or evidence of clinically severe interstitial lung disease Immunocompromised state, regardless of etiology

Contacts and Locations

Sponsors and Collaborators

Swedish Orphan Biovitrum

Locations

Pinnacle Research Group | Anniston, Alabama, United States, 36207 Arizona Arthritis & Rheumatology Research, PLLC | Sun City, Arizona, United States, 85351 Medvin Clinical Research | Covina, California, United States, 91722 Valerius Medical Group & Research Center | Los Alamitos, California, United States, 90720 ACRC Studies | Poway, California, United States, 92064 MD Strategies Research Center | San Diego, California, United States, 92119 Tekton Research - Fort Collins | Fort Collins, Colorado, United States, 80528 Helix Biomedics, LLC | Boynton Beach, Florida, United States, 33435 Clinical Research Of West Florida Incorporated | Clearwater, Florida, United States, 33765 Omegas Research Consultants LLC | DeBary, Florida, United States, 32713 Riverside Clinical Research | Edgewater, Florida, United States, 32132 Homestead Associates in Research,Inc | Homestead, Florida, United States, 33032 Health Awareness INC | Jupiter, Florida, United States, 33458 Panax Clinical Research | Miami Lakes, Florida, United States, 33014 Y & L Advance Health Care, Inc | Miami, Florida, United States, 33144 Well Pharma Medical Research, Corp | Miami, Florida, United States, 33173 Clinical Research of West Florida, Inc. | Tampa, Florida, United States, 33606 Conquest Research | Winter Park, Florida, United States, 32789 Better Health Clinical Research, Inc. | Newnan, Georgia, United States, 30265 Institute of Arthritis Research | Idaho Falls, Idaho, United States, 83404 Advanced Clinical Research (ACR) - Family Practice/General Medicine - Meridian | Meridian, Idaho, United States, 83642 L-MARC Research Center | Louisville, Kentucky, United States, 40213 Reseach Integrity, LLC | Owensboro, Kentucky, United States, 42303 Klein and Associates, M.D., P.A. | Cumberland, Maryland, United States, 21502 Klein and Associates, M.D., P.A. | Hagerstown, Maryland, United States, 21740 Clinical Pharmacology Study Group | Worcester, Massachusetts, United States, 01605 Elite Clinical Research, LLC | Jackson, Mississippi, United States, 39216 Arthritis Consultants, Inc. | Saint Louis, Missouri, United States, 63141 Montana Medical Research, Inc. | Missoula, Montana, United States, 59808 Medex Healthcare Research, Inc. | New York, New York, United States, 10036 CFA - Cape Fear Arthritis Care, PLLC | Leland, North Carolina, United States, 28451 New Horizons Clinical Research | Cincinnati, Ohio, United States, 45242 Arthritis & Rheumatology Center of Oklahoma, PLLC | Oklahoma City, Oklahoma, United States, 73102 West Tennessee Research Institute | Jackson, Tennessee, United States, 38305 Metroplex Clinical Research Center | Dallas, Texas, United States, 75231 Pioneer Research Solutions, Inc. | Houston, Texas, United States, 77099 Southwest Rheumatology Research LLC | Mesquite, Texas, United States, 75150 AIM Trials - Internal Medicine | Plano, Texas, United States, 75234 Epic Medical Research | Red Oak, Texas, United States, 75154 Clinical Research Partners, LLC | Richmond, Virginia, United States, 23220

More Information

Additional Relevant MeSH Terms

• Gout
• Arthritis
• Joint Diseases
• Musculoskeletal Diseases
• Crystal Arthropathies
• Rheumatic Diseases
• Purine-Pyrimidine Metabolism, Inborn Errors
• Metabolism, Inborn Errors
• Genetic Diseases, Inborn
• Metabolic Diseases