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)
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Protalix
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Males or females ≥18 years of age.
- •Weight within the range of 50.0 - 150.0 kg.
- •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.
- •Willing to discontinue any oral ULT
- •Females who are sterile, postmenopausal, or non-pregnant and using birth control methods.
Exclusion Criteria
- •Any condition known to have arthritis as a clinical manifestation.
- •Positive testing for HBV,HCV, or HIV.
- •The patient is a pregnant or lactating female or plans to become pregnant during the study period.
- •Known allergy or sensitivity to the injected proteins, including pegylated products.
- •Prior exposure to any experimental or marketed uricase.
- •Patient treated with a medication known to have an influence on urate metabolism or clearance such as ULTs.
- •History of anaphylaxis, severe allergic reactions, or severe atopy.
- •G6PD deficiency or known catalase deficiency.
- •History of significant hematologic or autoimmune disorders within 5 years of Screening and/or patient is immunocompromised or treated with immunosuppressive medications.
- •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).
Arms & Interventions
E4W with placebo-MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
Intervention: PRX-115 (Biological)
E4W with placebo-MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
Intervention: Placebo-Methotrexate (Other)
E4W with MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with MTX
Intervention: PRX-115 (Biological)
E4W with MTX
IV infusion of PRX-115 every 4 weeks (E4W) for a total of 6 doses with MTX
Intervention: Methotrexate (MTX) (Drug)
E6W with MTX
IV infusion of PRX-115 every 6 weeks (E6W) for a total of 4 doses with MTX
Intervention: PRX-115 (Biological)
E6W with MTX
IV infusion of PRX-115 every 6 weeks (E6W) for a total of 4 doses with MTX
Intervention: Methotrexate (MTX) (Drug)
E8W with MTX
IV infusion of PRX-115 every 8 weeks (E8W) for a total of 3 doses with MTX
Intervention: PRX-115 (Biological)
E8W with MTX
IV infusion of PRX-115 every 8 weeks (E8W) for a total of 3 doses with MTX
Intervention: Methotrexate (MTX) (Drug)
placebo E4W
infusion of PRX-115 placebo every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
Intervention: PRX-115 placebo (Other)
placebo E4W
infusion of PRX-115 placebo every 4 weeks (E4W) for a total of 6 doses with placebo-MTX
Intervention: Placebo-Methotrexate (Other)
placebo E6W
IV infusion of PRX-115 placebo every 6 weeks (E6W) for a total of 4 doses with placebo-MTX
Intervention: PRX-115 placebo (Other)
placebo E6W
IV infusion of PRX-115 placebo every 6 weeks (E6W) for a total of 4 doses with placebo-MTX
Intervention: Placebo-Methotrexate (Other)
Outcomes
Primary Outcomes
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Time Frame: 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 Outcomes
- Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) at different time points(3 to 6 months of treatment)
- Treatment-emergent adverse events (TEAEs)(From enrollment to 8 months of study)