Clinical trial NCT04513366: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy
Official title: A Randomized Double-Blind, Placebo-Controlled Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Gout
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2020-08-14
Enrollment: 112
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 will be 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 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).

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:

   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

Primary outcomes:
measure: Serum uric acid control during month 6
timeFrame: 6 months
Secondary outcomes:
measure: Reduction of mean serum uric acid
timeFrame: 6 months
measure: Percent reduction of mean serum uric acid
timeFrame: 6 months
measure: SF-36
timeFrame: 6 months
measure: Tophus burden
timeFrame: 6 months
measure: Serum uric acid control in patients with tophi
timeFrame: 6 months
measure: Tender and Swollen Joint Counts
timeFrame: 6 months
measure: HAQ-DI
timeFrame: 6 months
measure: Gout Flare Incidence
timeFrame: 6 months
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group
state: Alabama
city: Sun City
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group & Research Center
state: California
city: Poway
country: United States
facility: ACRC Studies
state: California
city: San Diego
country: United States
facility: MD Strategies Research Center
state: California
city: Fort Collins
country: United States
facility: Tekton Research - Fort Collins
state: Colorado
city: Boynton Beach
country: United States
facility: Helix Biomedics, LLC
state: Florida
city: Clearwater
country: United States
facility: Clinical Research Of West Florida Incorporated
state: Florida
city: DeBary
country: United States
facility: Omegas Research Consultants LLC
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research,Inc
state: Florida
city: Jupiter
country: United States
facility: Health Awareness INC
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Y & L Advance Health Care, Inc
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research, Corp
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Newnan
country: United States
facility: Better Health Clinical Research, Inc.
state: Georgia
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Meridian
country: United States
facility: Advanced Clinical Research (ACR) - Family Practice/General Medicine - Meridian
state: Idaho
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Owensboro
country: United States
facility: Reseach Integrity, LLC
state: Kentucky
city: Cumberland
country: United States
facility: Klein and Associates, M.D., P.A.
state: Maryland
city: Hagerstown
country: United States
facility: Klein and Associates, M.D., P.A.
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Jackson
country: United States
facility: Elite Clinical Research, LLC
state: Mississippi
city: Saint Louis
country: United States
facility: Arthritis Consultants, Inc.
state: Missouri
city: Missoula
country: United States
facility: Montana Medical Research, Inc.
state: Montana
city: New York
country: United States
facility: Medex Healthcare Research, Inc.
state: New York
city: Leland
country: United States
facility: CFA - Cape Fear Arthritis Care, PLLC
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Arthritis & Rheumatology Center of Oklahoma, PLLC
state: Oklahoma
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research LLC
state: Texas
city: Plano
country: United States
facility: AIM Trials - Internal Medicine
state: Texas
city: Red Oak
country: United States
facility: Epic Medical Research
state: Texas
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
Study officials:
References: