A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy (DISSOLVE I)

A Randomized Double-Blind, Placebo-Controlled 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). Analysis of primary and key efficacy will be performed at Day 28 of Treatment Period 6. Safety was monitored throughout the study.

Study Overview

• Status: Completed
• Conditions: Chronic Gout
• Intervention / Treatment: Other: Normal Saline; Drug: SEL-212 low-dose; Drug: SEL-212 high-dose

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 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).

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

   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)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Normal saline	Other: Normal Saline; IV infusion of Normal Saline every 28 days for a total of up to 12 infusions
Experimental: 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
Experimental: 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; IV infusion of SEL-212 high-dose every 28 days for a total of up to 12 infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum uric acid control during month 6	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	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tender and Swollen Joint Counts	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	6 months
Tophus burden	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	6 months
HAQ-DI	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	6 months
SF-36	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	6 months
Gout Flare Incidence	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	6 months
Reduction of mean serum uric acid	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	6 months
Percent reduction of mean serum uric acid	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	6 months
Serum uric acid control in patients with tophi	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 months

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): July 21, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: August 7, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Metabolism, Inborn Errors; Crystal Arthropathies; Purine-Pyrimidine Metabolism, Inborn Errors; Gout
• Other Study ID Numbers: SEL-212/301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No