Clinical trial NCT05745727: A Study to Evaluate the Safety, Tolerability, PK, and PD Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels
Official title: A Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gout
Keywords: Uricase
Gout
Uric acid
PRX-115
hyperuricemia
Lead sponsor: Protalix
Sponsor class: INDUSTRY
First posted: 2023-02-27
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, double-blind, placebo-controlled, single ascending dose study in participants with elevated uric acid levels. This study will be conducted in approximately 64 adult male and female participants in the dose escalation phase.

Detailed description: Participants will be assigned to 1 of 8 sequential dosing cohorts, each composed of 8 participants (6 active + 2 placebo) who will receive a single dose of PRX-115 or placebo by intravenous (IV) infusion.

Eligibility criteria: Inclusion Criteria:

1. Males or females 18 to 65 years of age, inclusive.
2. Serum uric acid greater than 6.0 mg/dL (0.35 mmol/L) at the Screening visit.
3. Body mass index within the range 18.5 to 40 kg/m\^2, inclusive, at the Screening visit.
4. Women of childbearing potential may be included only if they have a negative beta human chorionic gonadotropin (β-hCG) test result at Screening.
5. Men and women of childbearing potential and their partners should use double barrier contraception.

Exclusion Criteria:

1. Has any condition known to have arthritis as a clinical manifestation
2. Had greater than or equal to 1 gout flare in the last year prior to either Screening or Day -1.
3. Has clinical evidence of subcutaneous tophi at either Screening or Day -1.
4. Estimated glomerular filtration rate (eGFR) value less than or equal to 60 mL/min/1.73m\^2
5. History of significant renal disease, and/or presence of renal stones at either Screening or Day -1.
6. Has a history of anaphylaxis, severe allergic reactions, or severe atopy.
7. History of autoimmune disorders, and/or participant is immunocompromised or treated with immunosuppressive medications.
8. Has evidence of cardiovascular or cerebrovascular disease.
9. History of congestive heart failure, New York Heart Association Class III or IV.
10. BP outside the range of 90 to 150 mm Hg for systolic or 50 to 95 mm Hg for diastolic.
11. Participants with hypertension who are not on stable medication for at least 6 months.
12. Has uncontrolled type 2 diabetes
13. Concurrent treatment with urate lowering drugs (ULDs).
14. Prior exposure to any experimental or marketed uricase (eg, rasburicase \[Elitek, Fasturtec\], pegloticase \[Krystexxa®\], pegadricase \[SEL-212\]).
15. Glucose-6-phosphate dehydrogenase (G6PD) deficiency or known catalase deficiency.

Primary outcomes:
measure: Number of participants with adverse events receiving PRX-115 compared to placebo
timeFrame: Day 0 - Day 85
measure: Number of participants with abnormal clinically significant clinical laboratory results
timeFrame: Day 0 - Day 85
measure: Number of participants with abnormal clinical vital signs
timeFrame: Day 0 - Day 85
measure: Number of participants with abnormal clinically significant results from physical examination
timeFrame: Day 0 - Day 85
measure: Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
timeFrame: Day 0 - Day 85
Secondary outcomes:
measure: PK of PRX-115: Maximum observed plasma drug concentration (Cmax)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-t)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: Time to maximum observed plasma drug concentration (Tmax)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: total body clearance (CL)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: volume of distribution during the terminal phase (Vd)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: Terminal elimination half-life (T ½)
timeFrame: Day 1 - Day 85
measure: PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-inf)
timeFrame: Day 1 - Day 85
measure: Pharmacodynamics of PRX-115: blood uric acid levels
timeFrame: Day 0 - Day 85
measure: Immunogenicity of PRX-115: measurement of anti-drug antibody levels
timeFrame: Day 1 - Day 85
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: New Zealand Clinical Research
state: Auckland
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
Study officials:
affiliation: New Zealand Clinical Research
name: Mark Marshall, Dr.
role: PRINCIPAL_INVESTIGATOR
References: