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

NCT ID: NCT04596540

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-30
• Study Completion Date: 2023-01-12

Brief Summary

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). Analysis of primary and key efficacy were performed at Day 28 of Treatment Period 6. Safety was monitored throughout the study.

Detailed 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 high-dose) via IV infusion. The placebo consisted of normal saline.

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).

Conditions

Chronic Gout

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

SEL-212 low-dose

IV infusion of SEL-212 low-dose every 28 days for a total of up to 6 infusions

Group Type: EXPERIMENTAL

SEL-212 low-dose

Intervention Type: DRUG

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) Other Names: SEL-110, ImmTOR

SEL-212 high-dose

IV infusion of SEL-212 high-dose every 28 days for a total of up to 6 infusions

Group Type: EXPERIMENTAL

SEL-212 high-dose

Intervention Type: DRUG

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) Other Names: SEL-110, ImmTOR

Placebo

IV infusion of Normal Saline every 28 days for a total of up to 6 infusions

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline

Interventions

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) Other Names: SEL-110, ImmTOR

Intervention Type: DRUG

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) Other Names: SEL-110, ImmTOR

Intervention Type: DRUG

Placebo

Normal saline

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. 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;

2. History of symptomatic gout defined as:

1. ≥ 3 gout flares within 18 months of Screening or

2. Presence of ≥ 1 gout tophus or

3. Current diagnosis of gouty arthritis

3. 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:

1. > 6 weeks after hysterectomy with or without surgical bilateral salpingo-oophorectomy or

2. Post-menopausal (> 24 months of natural amenorrhea or in the absence of >24 months of amenorrhea, one documented confirmatory FSH measurement)

4. 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;

5. Has at the Screening Visit SUA ≥ 7 mg/dL

6. Negative serology for HIV-1/-2 and negative antigen to hepatitis B and negative antibodies to hepatitis C;

Exclusion Criteria

1. Has a history of anaphylaxis, severe allergic reactions, or severe atopy;

2. 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®);

3. 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.

4. 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.

5. Had major surgery within 3 months of initial screening.

6. 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.

7. Has uncontrolled diabetes at Screening with HbA1c ≥ 8.5%;

8. Has fasting Screening glucose > 240 mg/dL;

9. Has fasting Screening triglyceride > 500 mg/dL;

10. Has fasting Screening low-density lipoprotein (LDL) > 200 mg/dL;

11. Has glucose-6-phosphate dehydrogenase (G6PD) deficiency;

12. Has uncontrolled hypertension defined as blood pressure > 170/100 mmHg at Screening and 1 week prior to dosing

13. 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

14. Is receiving ongoing treatment for arrhythmia, including placement of an implantable defibrillator, unless considered stable and on active treatment;

15. 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;

16. Has congestive heart failure, New York Heart Association Class III or IV;

17. 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;

18. History of significant hematological disorders within 5 years or autoimmune disorders, and/or patient is currently immunosuppressed or immunocompromised;

19. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®®), pegadricase (SEL 037))

20. Patient has received a live vaccine in the previous 6 months.

21. Patient is planning to receive any live vaccine during the study.

22. History of malignancy within the last 5 years other than basal skin cancer;

23. Patients with a documented history of moderate or severe alcohol or substance use disorder within the 12 months prior to randomization.

24. History of or evidence of clinically severe interstitial lung disease

25. Immunocompromised state, regardless of etiology

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Swedish Orphan Biovitrum AB (publ)

Locations

Clinical Research Of West Florida Incorporated

Clearwater, Florida, United States

Omegas Research Consultants LLC

DeBary, Florida, United States

Sweet Hope Research Specialty, Inc

Hialeah, Florida, United States

Homestead Associates in Research,Inc

Miami, Florida, United States

D&H National Research Centers

Miami, Florida, United States

Panax Clinical Research

Miami Lakes, Florida, United States

Napa Research

Pompano Beach, Florida, United States

Clinical Research of West Florida, Inc.

Tampa, Florida, United States

Conquest Research

Winter Park, Florida, United States

Horizon Clinical Research

Fayetteville, Georgia, United States

Arthritis Center of North Georgia, LLC

Gainesville, Georgia, United States

Injury Care Medical Center

Boise, Idaho, United States

Great Lakes Clinical Trials at Ravenswood Rheumatology

Chicago, Illinois, United States

Great Lakes Clinical Trials LLC

Chicago, Illinois, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

University Of Michigan

Ann Arbor, Michigan, United States

Elite Clinical Research, LLC

Jackson, Mississippi, United States

Rutgers- New Jersey Medical School

Newark, New Jersey, United States

Medication Management of Greensboro

Greensboro, North Carolina, United States

Triad Clinical Trials

Greensboro, North Carolina, United States

Carolina Research Center, Inc

Shelby, North Carolina, United States

META Medical Research Institute LLC

Dayton, Ohio, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

New Phase Research and Development

Knoxville, Tennessee, United States

Amarillo Center for Clinical Research, Ltd.

Amarillo, Texas, United States

Heritage Rheumatology and Arthritis Care

Colleyville, Texas, United States

Pioneer Research Solutions, Inc.

Houston, Texas, United States

Southwest Rheumatology Research LLC

Mesquite, Texas, United States

AIM Trials - Internal Medicine

Plano, Texas, United States

Arthritis Northwest, PLLC - Research

Spokane, Washington, United States

Aleksandre Aladashvili Clinic LLC

Tbilisi, , Georgia

LTD Israeli-Georgian Medical Research Clinic "Helsicore"

Tbilisi, , Georgia

JSC "Evex Hospitals"

Tbilisi, , Georgia

LTD MediClub Georgia

Tbilisi, , Georgia

LTD Georgian-Dutch Hospital

Tbilisi, , Georgia

LTD "The First Medical Center"

Tbilisi, , Georgia

Republican Hospital n.a. V.A. Baranov

Petrozavodsk, Kareliya, Respublika, Russia

Research Institute of Rheumatology n.a. Nasonova

Moscow, Moscow, Russia

GBOU VPO Orenburg State Medical University

Orenburg, Orenburg Oblast, Russia

Ryazan State Medical University n. a. I.P. Pavlov

Ryazan, Ryazan Oblast, Russia

Clinical Rheumatological Hospital #25

Saint Petersburg, Sankt-Peterburg, Russia

Medical-sanitary unit #157 - Rheumatology

Saint Petersburg, Sankt-Peterburg, Russia

Institute for Treatment and Rehabilitation Niska Banja

Niška Banja, Nišavski Okrug, Serbia

Institute for Rheumatology - Rheumatology

Belgrade, , Serbia

Institute for Rheumatology

Belgrade, , Serbia

Military Medical Academy

Belgrade, , Serbia

Clinical Hospital Center Bezanisjka Kosa

Belgrade, , Serbia

Tovarystvo z obmezhenoi vidpov

Kyiv, Kyïv, Ukraine

Naukovo-Doslidnyi Inst. Reabil

Vinnytsia, Vinnytsia Oblast, Ukraine

Medychnyi tsentr Tovarystva z

Zaporizhzhia, Zaporizhzhia Oblast, Ukraine

Cherkaska Oblasna likarnia

Cherkasy, , Ukraine

Kyivska klinichna likarnia na

Kyiv, , Ukraine

Vinnytska Oblasna klinichna likarnia imeni M.I

Vinnytsia, , Ukraine

Countries

United States; Georgia; Russia; Serbia; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-003070-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SEL-212/302

Identifier Type: -

Identifier Source: org_study_id