A Study to Evaluate the Safety, Tolerability, PK, and PD Properties of PRX-115 in Adult Volunteers With Elevated Uric Acid Levels
Study Details
Study Description
Brief Summary
This is a Phase 1, double-blind, placebo-controlled, single dose-ascending study in participants with elevated uric acid levels. This study will be conducted in approximately 56 adult male and female participants in the dose escalation phase.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Participants will be assigned to 1 of 7 sequential dosing cohorts, each composed of 8 (6 active + 2 placebo) participants who will receive a single dose of PRX-115 or placebo by intravenous (IV) infusion.
Study Design
Arms and Interventions
| 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 7
Other Names:
|
| 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 7
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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: 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).
- 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).
- 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
- Immunogenicity of PRX-115: measurement of anti-drug antibody levels [Day 1 - Day 85]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Males or females 18 to 65 years of age, inclusive.
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Serum uric acid greater than 6.0 mg/dL (0.35 mmol/L) at the Screening visit.
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Body mass index within the range 18.5 to 40 kg/m^2, inclusive, at the Screening visit.
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Women of childbearing potential may be included only if they have a negative beta human chorionic gonadotropin (β-hCG) test result at Screening.
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Men and women of childbearing potential and their partners should use double barrier contraception.
Exclusion Criteria:
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Has any condition known to have arthritis as a clinical manifestation
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Had greater than or equal to 1 gout flare in the last year prior to either Screening or Day -1.
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Has clinical evidence of subcutaneous tophi at either Screening or Day -1.
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Estimated glomerular filtration rate (eGFR) value less than or equal to 60 mL/min/1.73m^2
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History of significant renal disease, and/or presence of renal stones at either Screening or Day -1.
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Has a history of anaphylaxis, severe allergic reactions, or severe atopy.
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History of autoimmune disorders, and/or participant is immunocompromised or treated with immunosuppressive medications.
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Has evidence of cardiovascular or cerebrovascular disease.
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History of congestive heart failure, New York Heart Association Class III or IV.
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BP outside the range of 90 to 150 mm Hg for systolic or 50 to 95 mm Hg for diastolic.
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Participants with hypertension who are not on stable medication for at least 6 months.
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Has uncontrolled type 2 diabetes
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Concurrent treatment with urate lowering drugs (ULDs).
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Prior exposure to any experimental or marketed uricase (eg, rasburicase [Elitek, Fasturtec], pegloticase [Krystexxa®], pegadricase [SEL-212]).
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Glucose-6-phosphate dehydrogenase (G6PD) deficiency or known catalase deficiency.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Zealand Clinical Research | Grafton | Auckland | New Zealand | 1010 |
| 2 | New Zealand Clinical Research | Christchurch | New Zealand | 8011 |
Sponsors and Collaborators
- Protalix
Investigators
- Principal Investigator: Mark Marshall, Dr., New Zealand Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PB115-SAD-101