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

Chronic Gout Clinical Trial

— DISSOLVE II  

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: NCT04596540
• Other study ID #: SEL-212/302
• Secondary ID: 2020-003070-45
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2020
• Est. completion date: January 12, 2023

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 were 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 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: January 12, 2023
• Est. primary completion date: January 10, 2023
• 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:

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

Related Conditions & MeSH terms

• Chronic Gout
• Gout

Intervention

Drug:
• 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) Other Names: SEL-110, ImmTOR
• 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) Other Names: SEL-110, ImmTOR

Other:
• Placebo
Normal saline

Locations

Country	Name	City	State
Georgia	Aleksandre Aladashvili Clinic LLC	Tbilisi
Georgia	JSC "Evex Hospitals"	Tbilisi
Georgia	LTD "The First Medical Center"	Tbilisi
Georgia	LTD Georgian-Dutch Hospital	Tbilisi
Georgia	LTD Israeli-Georgian Medical Research Clinic "Helsicore"	Tbilisi
Georgia	LTD MediClub Georgia	Tbilisi
Russian Federation	Research Institute of Rheumatology n.a. Nasonova	Moscow	Moskva
Russian Federation	GBOU VPO Orenburg State Medical University	Orenburg	Orenburgskaya Oblast
Russian Federation	Republican Hospital n.a. V.A. Baranov	Petrozavodsk	Kareliya, Respublika
Russian Federation	Ryazan State Medical University n. a. I.P. Pavlov	Ryazan	Ryazanskaya Oblast
Russian Federation	Clinical Rheumatological Hospital #25	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Medical-sanitary unit #157 - Rheumatology	Saint-Petersburg	Sankt-Peterburg
Serbia	Clinical Hospital Center Bezanisjka Kosa	Belgrade
Serbia	Institute for Rheumatology	Belgrade
Serbia	Institute for Rheumatology - Rheumatology	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Institute for Treatment and Rehabilitation Niska Banja	Niska Banja	Nišavski Okrug
Ukraine	Cherkaska Oblasna likarnia	Cherkasy
Ukraine	Kyivska klinichna likarnia na	Kyiv
Ukraine	Tovarystvo z obmezhenoi vidpov	Kyiv	Kyïv
Ukraine	Naukovo-Doslidnyi Inst. Reabil	Vinnytsia	Vinnyts'ka Oblast'
Ukraine	Vinnytska Oblasna klinichna likarnia imeni M.I	Vinnytsia
Ukraine	Medychnyi tsentr Tovarystva z	Zaporizhzhia	Zaporiz'ka Oblast'
United States	Amarillo Center for Clinical Research, Ltd.	Amarillo	Texas
United States	University Of Michigan	Ann Arbor	Michigan
United States	Injury Care Medical Center	Boise	Idaho
United States	Great Lakes Clinical Trials at Ravenswood Rheumatology	Chicago	Illinois
United States	Great Lakes Clinical Trials LLC	Chicago	Illinois
United States	Clinical Research Of West Florida Incorporated	Clearwater	Florida
United States	Heritage Rheumatology and Arthritis Care	Colleyville	Texas
United States	META Medical Research Institute LLC	Dayton	Ohio
United States	Omegas Research Consultants LLC	DeBary	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Horizon Clinical Research	Fayetteville	Georgia
United States	Arthritis Center of North Georgia, LLC	Gainesville	Georgia
United States	Medication Management of Greensboro	Greensboro	North Carolina
United States	Triad Clinical Trials	Greensboro	North Carolina
United States	Sweet Hope Research Specialty, Inc	Hialeah	Florida
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Elite Clinical Research, LLC	Jackson	Mississippi
United States	New Phase Research and Development	Knoxville	Tennessee
United States	Southwest Rheumatology Research LLC	Mesquite	Texas
United States	D&H National Research Centers	Miami	Florida
United States	Homestead Associates in Research,Inc	Miami	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Rutgers- New Jersey Medical School	Newark	New Jersey
United States	AIM Trials - Internal Medicine	Plano	Texas
United States	Napa Research	Pompano Beach	Florida
United States	Carolina Research Center, Inc	Shelby	North Carolina
United States	Arthritis Northwest, PLLC - Research	Spokane	Washington
United States	Clinical Research of West Florida, Inc.	Tampa	Florida
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Countries where clinical trial is conducted

United States,  Georgia,  Russian Federation,  Serbia,  Ukraine, 

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) < 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	6 months
Secondary	Reduction of mean serum 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 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 assessments 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) < 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	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