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

Phase 3

Completed

• Conditions: Chronic Gout
• Interventions: Drug: SEL-212 high-dose; Other: Placebo; Drug: SEL-212 low-dose

• Registration Number: NCT04596540
• Lead Sponsor: Swedish Orphan Biovitrum

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).

Study Timeline

• Study First Submitted: 2020-10-15
• Study First Submitted QC: 2020-10-15
• Study First Posted: 2020-10-22
• Study Start: 2020-11-30
• Primary Completion: 2023-01-10
• Study Completion: 2023-01-12
• Disposition First Submitted: 2023-12-11
• Disposition First Posted: 2023-12-13
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-16
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 153

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SEL-212 high-dose	SEL-212 high-dose	IV infusion of SEL-212 high-dose every 28 days for a total of up to 6 infusions
Placebo	Placebo	IV infusion of Normal Saline every 28 days for a total of up to 6 infusions
SEL-212 low-dose	SEL-212 low-dose	IV infusion of SEL-212 low-dose every 28 days for a total of up to 6 infusions

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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
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
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
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
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
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

Trial Locations

Locations (53)

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

Panax Clinical Research; 🇺🇸 Miami Lakes, Florida, United States

Homestead Associates in Research,Inc; 🇺🇸 Miami, Florida, United States

D&H National Research Centers; 🇺🇸 Miami, 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

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