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

Gout Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05745727
• Other study ID #: PB115-SAD-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 23, 2023
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Protalix
• Contact: Orit Cohen-Barak, PhD
• Phone: +972-4-9052-8100
• Email: Orit.Barak[@]protalix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Gout

Intervention

Drug:
• PRX-115
Escalating doses of PRX-115 will be given in different cohorts i.e., Cohorts 1 through 8
• Placebo
Escalating doses of Placebo will be given in different cohorts i.e., Cohorts 1 through 8

Locations

Country	Name	City	State
New Zealand	New Zealand Clinical Research	Christchurch
New Zealand	New Zealand Clinical Research	Grafton	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Protalix

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants with abnormal clinically significant clinical laboratory results	Clinical laboratory tests include hematology, coagulation and biochemistry	Day 0 - Day 85
Primary	Number of participants with abnormal clinical vital signs	Vital signs include pulse rate, blood pressure, respiratory rate and tympanic temperature	Day 0 - Day 85
Primary	Number of participants with abnormal clinically significant results from physical examination		Day 0 - Day 85
Primary	Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters		Day 0 - Day 85
Secondary	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
Secondary	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
Secondary	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
Secondary	PK of PRX-115: total body clearance (CL)	The PK parameter calculated will be total body clearance (CL).	Day 1 - Day 85
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Immunogenicity of PRX-115: measurement of anti-drug antibody levels		Day 1 - Day 85