A Study to Evaluate the Safety, Tolerability, PK, and PD Properties of PRX-115 in Adult Volunteers with Elevated Uric Acid Levels

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.

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.

Study Overview

• Status: Completed
• Conditions: Gout
• Intervention / Treatment: Drug: PRX-115; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • New Zealand Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRX-115; Participants will receive a single dose of PRX-115 by IV infusion	Drug: PRX-115; Escalating doses of PRX-115 will be given in different cohorts i.e., Cohorts 1 through 8; Other Names: Escalating doses of PRX-115
Placebo Comparator: Placebo; Participants will receive a single dose of placebo by IV infusion	Drug: Placebo; Escalating doses of Placebo will be given in different cohorts i.e., Cohorts 1 through 8; Other Names: Placebo to match

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events receiving PRX-115 compared to placebo	To assess the safety and tolerability of a single infusion of PRX-115 as assessed by frequency of drug related adverse events, graded by severity.	Day 0 - Day 85
Number of participants with abnormal clinically significant clinical laboratory results	Clinical laboratory tests include hematology, coagulation and biochemistry	Day 0 - Day 85
Number of participants with abnormal clinical vital signs	Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature	Day 0 - Day 85
Number of participants with abnormal clinically significant results from physical examination		Day 0 - Day 85
Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters		Day 0 - Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of PRX-115: Maximum observed plasma drug concentration (Cmax)	The Cmax PK parameter calculated based on the observed plasma drug concentration versus time curve	Day 1 - Day 85
PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-t)	The PK parameter calculated will be Area under the plasma drug concentration-time curve of the last measurable drug concentration (AUC0-t).	Day 1 - Day 85
PK of PRX-115: Time to maximum observed plasma drug concentration (Tmax)	The PK parameter calculated will be Time to maximum observed plasma drug concentration (T max).	Day 1 - Day 85
PK of PRX-115: total body clearance (CL)	The PK parameter calculated will be total body clearance (CL).	Day 1 - Day 85
PK of PRX-115: volume of distribution during the terminal phase (Vd)	The PK parameter calculated will be volume of distribution during the terminal phase (Vd).	Day 1 - Day 85
PK of PRX-115: Terminal elimination half-life (T ½)	The PK parameter of Terminal elimination half-life (T ½) is calculated based on the plasma drug concentration-time curve	Day 1 - Day 85
PK of PRX-115: Area under the plasma concentration versus time curve (AUC 0-inf)	The PK parameters calculated will be Area under the plasma drug concentration-time curve from time 0 to infinity (AUC0-inf).	Day 1 - Day 85
Pharmacodynamics of PRX-115: blood uric acid levels	Pharmacodynamics of PRX-115 by measurement of blood uric acid levels over 85 days	Day 0 - Day 85
Immunogenicity of PRX-115: measurement of anti-drug antibody levels		Day 1 - Day 85

Collaborators and Investigators

• Sponsor: Protalix
• Investigators: Principal Investigator: Mark Marshall, Dr., New Zealand Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Actual): August 26, 2024
• Study Completion (Actual): February 6, 2025

Study Registration Dates

• First Submitted: February 3, 2023
• First Submitted That Met QC Criteria: February 16, 2023
• First Posted (Actual): February 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 9, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Gout; Uric acid; hyperuricemia; Uricase; PRX-115
• Other Study ID Numbers: PB115-SAD-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No