Gout
Conditions
Keywords
gout, uricase, uric acid, hyperuricemia, PRX-115
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled phase II study assessing the efficacy, safety, and dosing regimen selection of multiple IV infusions of PRX-115 over 24 weeks, with or without MTX, versus the respective placebos in adult patients with gout.
Detailed description
This study will evaluate the efficacy, safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PRX-115 (a recombinant pegylated Uricase) in adult patients with gout. Participants will receive PRX-115 by intravenous (IV) infusions according to different treatment schedules, with and without the immunomodulator methotrexate (MTX).
Interventions
BIOLOGICALPRX-115
intravenous (IV) infusion
DRUGMethotrexate (MTX)
Oral MTX 15 mg weekly
OTHERPRX-115 placebo
intravenous (IV) infusion
OTHERPlacebo-Methotrexate
Oral Placebo-MTX weekly
Sponsors
Protalix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Multiple IV infusions at a fixed dose per infusion, at different treatment intervals . For different dosing regimens, PRX-115 will be tested with and without the immunomodulator, MTX.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or females ≥18 years of age. 2. Weight within the range of 50.0 - 150.0 kg. 3. Gout patients who failed to normalize sUA (\<7 mg/dL) with or without xanthine oxidase inhibitors or uricosuric agent or have contraindications to these drugs. 4. Willing to discontinue any oral ULT 5. Females who are sterile, postmenopausal, or non-pregnant and using birth control methods.
Exclusion criteria
1. Any condition known to have arthritis as a clinical manifestation. 2. Positive testing for HBV,HCV, or HIV. 3. The patient is a pregnant or lactating female or plans to become pregnant during the study period. 4. Known allergy or sensitivity to the injected proteins, including pegylated products. 5. Prior exposure to any experimental or marketed uricase. 6. Patient treated with a medication known to have an influence on urate metabolism or clearance such as ULTs. 7. History of anaphylaxis, severe allergic reactions, or severe atopy. 8. G6PD deficiency or known catalase deficiency. 9. History of significant hematologic or autoimmune disorders within 5 years of Screening and/or patient is immunocompromised or treated with immunosuppressive medications. 10. Non-compensated CHF or hospitalization for CHF (Stage 3-4 NYHA Functional Class) within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled BP (\>160/100 mmHg) at screening and prior to randomization at Week -4 (Visit 1). 11. Current liver disease, as determined by ALT or AST levels above upper limit of normal at Screening Visit. 12. Chronic liver disease. 13. Hemoglobin \<11 g/dL, neutrophil count \<1500 /µl, or platelet count \<100,000 /µl. 14. Known severe pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. 15. eGFR ≤ 40 mL/min/1.73m2 tested at Screening Visit. Kidney transplant or requires dialysis. 16. Known intolerance and/or known contraindication to MTX treatment or MTX treatment considered inappropriate 17. Has uncontrolled type 2 diabetes at Screening with HbA1c ≥8.5%. Patients with type 1 diabetes will be excluded. 18. Has known latent autoimmune diabetes of adult. 19. Immunocompromised state, regardless of etiology. 20. History or treatment of malignancy in the last 5 years, excluding localized, nonmelanoma skin cancers (e.g. basal or squamous cell)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6 | 6 months of treatment | Proportion of patients who achieve a reduction in sUA to \<6.0 mg/dL for at least 80% of the time during Month 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) at different time points | 3 to 6 months of treatment | Proportion of patients that achieve a reduction in sUA to \<6.0 mg/dL for at least 80% of the time during Month 3 or 4, 5 and 6. |
| Treatment-emergent adverse events (TEAEs) | From enrollment to 8 months of study | Occurrence and severity of treatment-emergent adverse events (TEAEs) |
Countries
Georgia, Israel, United States
Contacts
CONTACTHead of Clinical Development
Outcome results
None listed