Multi-Dose Safety/Pharmacodynamic Study of SEL-212/SEL-037 in Subjects With Symptomatic Gout & Elevated Blood Uric Acid

Hyperuricemia Clinical Trial

Official title:

An Open Label Phase II Multiple Dose Safety, Pharmacokinetic and Pharmacodynamics Study of SEL-212 Followed by Open Label Administration of SEL-037 in Subjects With Symptomatic Gout and Elevated Blood Uric Acid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02959918
• Other study ID #: SEL-212/201
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: January 2019

Study information

• Verified date: January 2022
• Source: Selecta Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase (SEL-037) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in subjects with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses ( 5 monthly IV infusions) of pegsiticase (SEL-037) alone. Participants will be monitored for safety endpoints through the 5th treatment cycle plus 30 days .Pharmacokinetic samples will be drawn at pre-determined time points in addition to weekly serum uric acid levels.

Description:

This is an open label multicenter study to evaluate the safety and tolerability of multiple doses (3 monthly IV infusions) of SEL-212 ( a combination of pegsiticase ( SEL-037, also known as pegadricase) and SVP-rapamycin (SEL-110)) followed by multiple doses (2 monthly IV infusions) of pegsiticase (SEL-037) alone for a total of 5 treatment cycles in participants with symptomatic gout and hyperuricemia. Additional participants will be treated with multiple doses (5 monthly IV infusions) of pegsiticase (SEL-037) alone. Uricase is an enzyme that converts uric acid to the readily soluble allantoin that is then excreted and SEL-110 is designed to prevent unwanted anti-drug-antibodies (ADAs) from forming. All participants will be monitored for safety and tolerability to drug throughout the study on a weekly schedule. Pharmacokinetic and pharmacodynamic parameters will at specific timepoints to monitor for continued efficacy. Pharmacodynamic parameters measured include uric acid levels and levels of ADAs. The study duration per enrolled participant will be approximately 6 months including a 1 month screening period followed by 5 treatment cycles and an end of treatment visit which will occur 30 days after the last IV infusion .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: January 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Adult (age 21-75 inclusive) men and women of non child bearing potential with established or symptomatic gout which is defined as having at least ONE of any of the

3 following factors:

1. = 1 tophus

2. 1 gout flare within the last 6 months

3. Chronic gouty arthropathy

2. Screening serum uric acid of >6 mg/dL

3. On a gout flare prophylactic regimen for 7 days prior to first dose

4. Willing to provide written informed consent prior to first study procedure is performed.

5. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits.

Exclusion Criteria:

1. History of anaphylaxis or severe allergic reaction.

2. History of an allergy to pegylated products.

3. Women of child bearing potential, Defined as:

• <6 weeks after surgical bilateral salpingooperhectony with or without hysterectomy
• Pre or perimenopausal ( < less than 24 months of natural amenorrhea)

4. Initiation or change in dose of hormone-replacement therapy for menopausal women less than 1 month prior to the Screening Visit or during the Screening Phase would be exclusionary. If after being on a stable dose of hormone-replacement therapy for one month the patient may be considered for the study if she continues to meet all other inclusion and exclusion criteria

5. Uncontrolled diabetes with baseline HbA1c =8%;

6. Glucose-6-phosphate dehydrogenase deficiency;

7. Uncontrolled hypertension

8. Ongoing treatment for arrhythmia, including placement of an implantable defibrillator;

9. History of coronary artery disease, including myocardial infarction;

10. Congestive heart failure, New York Heart Association Class III or IV;

11. ECG with evidence of prior myocardial infarction, clinically significant arrhythmia, or other abnormalities that, in the opinion of the investigator, are consistent with significant underlying cardiac disease;

12. History of hematological or autoimmune disorders, is immunosuppressed or immunocompromised;

13. Prior exposure to any experimental or marketed uricase (e.g., rasburicase (Elitek, Fasturtec), pegloticase (Krystexxa®), pegsiticase (SEL-037)

14. History of malignancy within the last 5 years other than basal skin cancer;

15. Subjects who, in the opinion of the investigator, present with a condition that would compromise their safety or that would make study completion unlikely.

Related Conditions & MeSH terms

• Gout
• Gout Chronic
• Hyperuricemia

Intervention

Drug:
• SEL-212
SEL-212, biologic
• SEL-037
SEL-037, biologic
• SVP-rapamycin (SEL-110)
SVP-rapamycin, biologic

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials	Anaheim	California
United States	Advanced Clinical Research	Boise	Idaho
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	Omega Research Consultants LLC	DeBary	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Tri West Research Associates LLC	El Cajon	California
United States	Triad Clinical Trials LLC	Greensboro	North Carolina
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Irvine Center for Clinical Research Inc.	Irvine	California
United States	L-MARC	Louisville	Kentucky
United States	Compass Research LLC	Orlando	Florida
United States	Advanced Clinical Research	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Selecta Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of Multiple Intravenous Infusions of SEL-037 or SEL-212 as Assessed by the Percentage of Participants Experiencing Serious Adverse Events and Those Adverse Events Reported by 5 Percentage or More in the Safety Analysis Set	To determine the safety and tolerability of SEL-037 (pegadricase) after up to 5 monthly infusions, of SEL-212 for 3 monthly infusions followed by 2 monthly infusions of SEL-037 (pegadricase), or of SEL-212 for 5 monthly infusions as assessed by the percentage of participants in a treatment arm experiencing serious adverse events and percentage of participants experiencing those adverse events that were reported by 5 or more percentage of participants in any arm in the safety analysis set	Five monthly infusions
Secondary	Number of Participants With Reduced Serum Uric Acid After Multiple Monthly IV Infusions With or Without SEL-110	Measurement of the number of participants with reduced serum uric acid after multiple monthly infusions with or without SEL-110 as determined by values of sUA < 6 mg/dL at the end of Treatment Period 3 and at the end of Treatment Period 5 in eligible subjects	3 and 5 months