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

Phase 1

Completed

• Conditions: Gout
• Interventions: Drug: Placebo; Drug: PRX-115

• Registration Number: NCT05745727
• Lead Sponsor: Protalix

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.

Study Timeline

• Study First Submitted: 2023-02-03
• Study First Submitted QC: 2023-02-16
• Study First Posted: 2023-02-27
• Study Start: 2023-03-23
• Primary Completion: 2024-08-26
• Status Verified: 2025-02
• Study Completion: 2025-02-06
• Last Update Submitted: 2025-02-09
• Last Update Posted: 2025-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive a single dose of placebo by IV infusion
PRX-115	PRX-115	Participants will receive a single dose of PRX-115 by IV infusion

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events receiving PRX-115 compared to placebo	Day 0 - Day 85	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.
Number of participants with abnormal clinical vital signs	Day 0 - Day 85	Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature
Number of participants with abnormal clinically significant results from physical examination	Day 0 - Day 85
Number of participants with abnormal clinically significant clinical laboratory results	Day 0 - Day 85	Clinical laboratory tests include hematology, coagulation and biochemistry
Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters	Day 0 - Day 85

Secondary Outcome Measures

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

Trial Locations

Locations (1)

New Zealand Clinical Research; 🇳🇿 Christchurch, New Zealand