Clinical trial NCT04596540: A Study of SEL-212 in Patients With Gout Refractory to Conventional Therapy II
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: 2020-10-22
Enrollment: 153
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 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.

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).

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

Primary outcomes:
measure: Serum uric acid control during Month 6
timeFrame: 6 months
Secondary outcomes:
measure: Reduction of mean serum acid
timeFrame: 6 months
measure: Percent reduction of mean serum 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: 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: Hialeah
country: United States
facility: Sweet Hope Research Specialty, Inc
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research,Inc
state: Florida
city: Miami
country: United States
facility: D&H National Research Centers
state: Florida
city: Pompano Beach
country: United States
facility: Napa Research
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: Fayetteville
country: United States
facility: Horizon Clinical Research
state: Georgia
city: Gainesville
country: United States
facility: Arthritis Center of North Georgia, LLC
state: Georgia
city: Boise
country: United States
facility: Injury Care Medical Center
state: Idaho
city: Chicago
country: United States
facility: Great Lakes Clinical Trials at Ravenswood Rheumatology
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials LLC
state: Illinois
city: Wheaton
country: United States
facility: The Center for Rheumatology and Bone Research
state: Maryland
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Jackson
country: United States
facility: Elite Clinical Research, LLC
state: Mississippi
city: Newark
country: United States
facility: Rutgers- New Jersey Medical School
state: New Jersey
city: Greensboro
country: United States
facility: Medication Management of Greensboro
state: North Carolina
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: Shelby
country: United States
facility: Carolina Research Center, Inc
state: North Carolina
city: Dayton
country: United States
facility: META Medical Research Institute LLC
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Knoxville
country: United States
facility: New Phase Research and Development
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research, Ltd.
state: Texas
city: Colleyville
country: United States
facility: Heritage Rheumatology and Arthritis Care
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: Spokane
country: United States
facility: Arthritis Northwest, PLLC - Research
state: Washington
city: Tbilisi
country: Georgia
facility: Aleksandre Aladashvili Clinic LLC
city: Tbilisi
country: Georgia
facility: LTD Israeli-Georgian Medical Research Clinic "Helsicore"
city: Tbilisi
country: Georgia
facility: JSC "Evex Hospitals"
city: Tbilisi
country: Georgia
facility: LTD MediClub Georgia
city: Tbilisi
country: Georgia
facility: LTD Georgian-Dutch Hospital
city: Tbilisi
country: Georgia
facility: LTD "The First Medical Center"
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital n.a. V.A. Baranov
state: Kareliya, Respublika
city: Moscow
country: Russian Federation
facility: Research Institute of Rheumatology n.a. Nasonova
state: Moskva
city: Orenburg
country: Russian Federation
facility: GBOU VPO Orenburg State Medical University
state: Orenburgskaya Oblast
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University n. a. I.P. Pavlov
state: Ryazanskaya Oblast
city: Saint-Petersburg
country: Russian Federation
facility: Clinical Rheumatological Hospital #25
state: Sankt-Peterburg
city: Saint-Petersburg
country: Russian Federation
facility: Medical-sanitary unit #157 - Rheumatology
state: Sankt-Peterburg
city: Niska Banja
country: Serbia
facility: Institute for Treatment and Rehabilitation Niska Banja
state: Nišavski Okrug
city: Belgrade
country: Serbia
facility: Institute for Rheumatology - Rheumatology
city: Belgrade
country: Serbia
facility: Institute for Rheumatology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanisjka Kosa
city: Kyiv
country: Ukraine
facility: Tovarystvo z obmezhenoi vidpov
state: Kyïv
city: Vinnytsia
country: Ukraine
facility: Naukovo-Doslidnyi Inst. Reabil
state: Vinnyts'ka Oblast'
city: Zaporizhzhia
country: Ukraine
facility: Medychnyi tsentr Tovarystva z
state: Zaporiz'ka Oblast'
city: Cherkasy
country: Ukraine
facility: Cherkaska Oblasna likarnia
city: Kyiv
country: Ukraine
facility: Kyivska klinichna likarnia na
city: Vinnytsia
country: Ukraine
facility: Vinnytska Oblasna klinichna likarnia imeni M.I
Study officials:
affiliation: Selecta Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: