IV PRX-115 at different dose schedules, with or without methotrexate, versus placebo for adults with gout

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing the Efficacy, Safety, and Dosing Regimen Selection of Multiple Intravenous Infusions of PRX-115 With and Without Methotrexate Versus Placebo in Adult Patients With Gout (RELEASE)

This trial will test whether IV PRX-115 given on different schedules, with or without low-dose methotrexate, can lower uric acid and be safe in adults whose gout is not controlled by standard urate-lowering drugs.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Protalix (Industry-sponsored)
• Drugs / interventions: methotrexate
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT07280156 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial testing multiple IV infusions of PRX-115 over 24 weeks with treatment arms that include or omit methotrexate and matching placebos. Participants are assigned to different dosing regimens to identify the best balance of efficacy and tolerability. The study measures serum uric acid lowering, safety and tolerability, pharmacokinetics/pharmacodynamics, and immunogenicity (anti-drug antibodies). Dosing regimen selection will be informed by both clinical response and antibody/PK profiles.

Who should consider this trial

Good fit: Adults aged 18 or older with gout whose serum uric acid remains ≥7 mg/dL despite or who are intolerant/contraindicated to standard oral urate-lowering therapy, weighing 50–150 kg, willing to stop other ULTs and able to avoid pregnancy are the intended participants.

Not a fit: Patients who are pregnant or breastfeeding, have active hepatitis or HIV, G6PD deficiency, known allergy to pegylated proteins, prior exposure to any uricase, or whose gout is well controlled on current therapy are unlikely to benefit or may be ineligible.

Why it matters

Potential benefit: If successful, PRX-115 could provide a reliable way to lower serum uric acid and reduce gout flares for patients who do not respond to or cannot take standard urate-lowering therapies.

How similar studies have performed: Pegylated uricases (for example pegloticase) have reliably lowered serum uric acid but were limited by immune reactions, and recent data indicate that adding methotrexate can reduce immunogenicity, so this trial builds on both established efficacy and emerging strategies to improve durability.

Eligibility criteria

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)

Where this trial is running

Miami, Florida

• Bioclinical Research Alliance, Inc — Miami, Florida, United States (Recruiting)

Study contacts

• Study coordinator: Head of Clinical Development

Conditions Gout; gout; uricase; uric acid; hyperuricemia; PRX-115