A Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy

ClinicalTrials.gov processed this data on February 16, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

COMPLETED (See Contacts and Locations)
Verified February 2024 by Swedish Orphan Biovitrum

Sponsor

Swedish Orphan Biovitrum

Information Provided by (Responsible Party)

Swedish Orphan Biovitrum

Clinicaltrials.gov Identifier

NCT04596540
Other Study ID Numbers: SEL-212/302
First Submitted: October 15, 2020
First Posted: October 22, 2020
Last Update Posted: February 20, 2024
Last Verified: February 2024
History of Changes

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

Placebo subjects who completed 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: Placebo

Study Design

Study TypeInterventional
Actual Enrollment153 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy
Study Start DateNovember 30, 2020
Actual Primary Completion DateJanuary 10, 2023
Actual Study Completion DateJanuary 12, 2023

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • SEL-212 low-dose
    • IV infusion of SEL-212 low-dose every 28 days for a total of up to 6 infusions
  • Drug: 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
  • SEL-212 high-dose
    • IV infusion of SEL-212 high-dose every 28 days for a total of up to 6 infusions
  • Drug: SEL-212 high-dose
    • Placebo
      • IV infusion of Normal Saline every 28 days for a total of up to 6 infusions
    • Other: Placebo

      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) < 6mg/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 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 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 assessments 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) < 6mg/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:
      • > 6 weeks after hysterectomy with or without surgical bilateral salpingo-oophorectomy or
      • 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
      • Clinical Research Of West Florida Incorporated | Clearwater, Florida, United States, 33765
      • Omegas Research Consultants LLC | DeBary, Florida, United States, 32713
      • Sweet Hope Research Specialty, Inc | Hialeah, Florida, United States, 33016
      • Panax Clinical Research | Miami Lakes, Florida, United States, 33014
      • Homestead Associates in Research,Inc | Miami, Florida, United States, 33032
      • D&H National Research Centers | Miami, Florida, United States, 33155
      • Napa Research | Pompano Beach, Florida, United States, 33064
      • Clinical Research of West Florida, Inc. | Tampa, Florida, United States, 33606
      • Conquest Research | Winter Park, Florida, United States, 32789
      • Horizon Clinical Research | Fayetteville, Georgia, United States, 30214
      • Arthritis Center of North Georgia, LLC | Gainesville, Georgia, United States, 30501
      • Injury Care Medical Center | Boise, Idaho, United States, 83713
      • Great Lakes Clinical Trials at Ravenswood Rheumatology | Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials LLC | Chicago, Illinois, United States, 60640
      • The Center for Rheumatology and Bone Research | Wheaton, Maryland, United States, 20902
      • University Of Michigan | Ann Arbor, Michigan, United States, 48109
      • Elite Clinical Research, LLC | Jackson, Mississippi, United States, 39202
      • Rutgers- New Jersey Medical School | Newark, New Jersey, United States, 07103
      • Medication Management of Greensboro | Greensboro, North Carolina, United States, 27408
      • Triad Clinical Trials | Greensboro, North Carolina, United States, 27410
      • Carolina Research Center, Inc | Shelby, North Carolina, United States, 28150
      • META Medical Research Institute LLC | Dayton, Ohio, United States, 45432
      • Altoona Center for Clinical Research | Duncansville, Pennsylvania, United States, 16635
      • New Phase Research and Development | Knoxville, Tennessee, United States, 37909
      • Amarillo Center for Clinical Research, Ltd. | Amarillo, Texas, United States, 79124
      • Heritage Rheumatology and Arthritis Care | Colleyville, Texas, United States, 76034
      • 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, 75074
      • Arthritis Northwest, PLLC - Research | Spokane, Washington, United States, 99204
      • Aleksandre Aladashvili Clinic LLC | Tbilisi, Georgia, 0102
      • LTD Israeli-Georgian Medical Research Clinic "Helsicore" | Tbilisi, Georgia, 0112
      • JSC "Evex Hospitals" | Tbilisi, Georgia, 0159
      • LTD MediClub Georgia | Tbilisi, Georgia, 0160
      • LTD Georgian-Dutch Hospital | Tbilisi, Georgia, 0172
      • LTD "The First Medical Center" | Tbilisi, Georgia, 0180
      • Republican Hospital n.a. V.A. Baranov | Petrozavodsk, Kareliya, Respublika, Russian Federation, 185019
      • Research Institute of Rheumatology n.a. Nasonova | Moscow, Moskva, Russian Federation, 115522
      • GBOU VPO Orenburg State Medical University | Orenburg, Orenburgskaya Oblast, Russian Federation, 460018
      • Ryazan State Medical University n. a. I.P. Pavlov | Ryazan, Ryazanskaya Oblast, Russian Federation, 390039
      • Clinical Rheumatological Hospital #25 | Saint-Petersburg, Sankt-Peterburg, Russian Federation, 190068
      • Medical-sanitary unit #157 - Rheumatology | Saint-Petersburg, Sankt-Peterburg, Russian Federation, 196066
      • Institute for Treatment and Rehabilitation Niska Banja | Niska Banja, Nišavski Okrug, Serbia, 18205
      • Institute for Rheumatology - Rheumatology | Belgrade, Serbia, 11000
      • Institute for Rheumatology | Belgrade, Serbia, 11000
      • Military Medical Academy | Belgrade, Serbia, 11000
      • Clinical Hospital Center Bezanisjka Kosa | Belgrade, Serbia, 11080
      • Tovarystvo z obmezhenoi vidpov | Kyiv, Kyïv, Ukraine, 02081
      • Naukovo-Doslidnyi Inst. Reabil | Vinnytsia, Vinnyts'ka Oblast', Ukraine, 21029
      • Medychnyi tsentr Tovarystva z | Zaporizhzhia, Zaporiz'ka Oblast', Ukraine, 69005
      • Cherkaska Oblasna likarnia | Cherkasy, Ukraine, 18009
      • Kyivska klinichna likarnia na | Kyiv, Ukraine, 03049
      • Vinnytska Oblasna klinichna likarnia imeni M.I | Vinnytsia, Ukraine, 21018
      Investigators

        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