Gout
Conditions
Keywords
Uricase, Gout, Uric acid, PRX-115, hyperuricemia
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.
Interventions
DRUGPRX-115
Escalating doses of PRX-115 will be given in different cohorts i.e., Cohorts 1 through 8
DRUGPlacebo
Escalating doses of Placebo will be given in different cohorts i.e., Cohorts 1 through 8
Sponsors
Protalix
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 clinically significant clinical laboratory results | Day 0 - Day 85 | Clinical laboratory tests include hematology, coagulation and biochemistry |
| 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 12-lead electrocardiogram (ECG) parameters | Day 0 - Day 85 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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). |
| 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 |
| Immunogenicity of PRX-115: measurement of anti-drug antibody levels | Day 1 - Day 85 | — |
| 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: 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: 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: 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). |
Countries
New Zealand
Outcome results
None listed