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

Chronic Gout Clinical Trial

— DISSOLVE I  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04513366
• Other study ID #: SEL-212/301
• Status: Completed
• Phase: Phase 3
• Start date: August 18, 2020
• Est. completion date: December 1, 2022

Study information

• Verified date: February 2024
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: December 1, 2022
• Est. primary completion date: July 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Gout
• Gout

Intervention

Drug:
• SEL-212 low-dose
IV infusion of SEL-212 low-dose every 28 days for a total of up to 12 infusions
• SEL-212 high-dose
IV infusion of SEL-212 high-dose every 28 days for a total of up to 12 infusions

Other:
• Normal Saline
IV infusion of Normal Saline every 28 days for a total of up to 12 infusions

Locations

Country	Name	City	State
United States	Pinnacle Research Group	Anniston	Alabama
United States	Helix Biomedics, LLC	Boynton Beach	Florida
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Clinical Research Of West Florida Incorporated	Clearwater	Florida
United States	Medvin Clinical Research	Covina	California
United States	Klein and Associates, M.D., P.A.	Cumberland	Maryland
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Omegas Research Consultants LLC	DeBary	Florida
United States	Riverside Clinical Research	Edgewater	Florida
United States	Tekton Research - Fort Collins	Fort Collins	Colorado
United States	Klein and Associates, M.D., P.A.	Hagerstown	Maryland
United States	Homestead Associates in Research,Inc	Homestead	Florida
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	Elite Clinical Research, LLC	Jackson	Mississippi
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Health Awareness INC	Jupiter	Florida
United States	CFA - Cape Fear Arthritis Care, PLLC	Leland	North Carolina
United States	Valerius Medical Group & Research Center	Los Alamitos	California
United States	L-MARC Research Center	Louisville	Kentucky
United States	Advanced Clinical Research (ACR) - Family Practice/General Medicine - Meridian	Meridian	Idaho
United States	Southwest Rheumatology Research LLC	Mesquite	Texas
United States	Well Pharma Medical Research, Corp	Miami	Florida
United States	Y & L Advance Health Care, Inc	Miami	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Montana Medical Research, Inc.	Missoula	Montana
United States	Medex Healthcare Research, Inc.	New York	New York
United States	Better Health Clinical Research, Inc.	Newnan	Georgia
United States	Arthritis & Rheumatology Center of Oklahoma, PLLC	Oklahoma City	Oklahoma
United States	Reseach Integrity, LLC	Owensboro	Kentucky
United States	AIM Trials - Internal Medicine	Plano	Texas
United States	ACRC Studies	Poway	California
United States	Epic Medical Research	Red Oak	Texas
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Arthritis Consultants, Inc.	Saint Louis	Missouri
United States	MD Strategies Research Center	San Diego	California
United States	Arizona Arthritis & Rheumatology Research, PLLC	Sun City	Arizona
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	Conquest Research	Winter Park	Florida
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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