A Study to Investigate the Clinical Effect and the Safety of PRX-115 Infused Intravenously at Different Dosing Regimens, With and Without Methotrexate, Versus Placebo in Adults Gout Patients (RELEASE)

Protalix BioTherapeutics

Status and phase: Not yet enrolling; Phase 2

Conditions: Gout

Treatments: Drug: Methotrexate (MTX); Other: Placebo-Methotrexate; Biological: PRX-115; Other: PRX-115 placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07280156

PB115-GT-201

Details and patient eligibility

About

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.

Full 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).

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 6 patient groups, including a placebo group

E4W with placebo-MTX

Experimental group

Description:

IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with placebo-MTX

Treatment:

Biological: PRX-115

Other: Placebo-Methotrexate

E4W with MTX

Experimental group

Description:

IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with MTX

Treatment:

Biological: PRX-115

Drug: Methotrexate (MTX)

E6W with MTX

Experimental group

Description:

IV infusion of PRX-115 every 6 weeks (E6W) for a total of 4 doses with MTX

Treatment:

Biological: PRX-115

Drug: Methotrexate (MTX)

E8W with MTX

Experimental group

Description:

IV infusion of PRX-115 every 8 weeks (E8W) for a total of 3 doses + 3 doses of PRX-115 placebo every alternating 8 weeks with MTX

Treatment:

Biological: PRX-115

Drug: Methotrexate (MTX)

placebo E4W

Placebo Comparator group

Description:

infusion of PRX-115 placebo every 4 weeks (E4W) for a total of 6 doses with placebo-MTX

Treatment:

Other: PRX-115 placebo

Other: Placebo-Methotrexate

placebo E6W

Placebo Comparator group

Description:

IV infusion of PRX-115 placebo every 6 weeks (E6W) for a total of 4 doses with placebo-MTX

Treatment:

Other: PRX-115 placebo

Other: Placebo-Methotrexate