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)

Официальное название

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)

Обзор

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.

Подробное описание

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).

Вмешательства

• Биопрепарат PRX-115
  intravenous (IV) infusion
• Препарат Methotrexate (MTX)
  Oral MTX 15 mg weekly
• Другое PRX-115 placebo
  intravenous (IV) infusion
• Другое Placebo-Methotrexate
  Oral Placebo-MTX weekly

Первичные конечные точки

• Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6 [Срок оценки: 6 months of treatment]

Вторичные конечные точки (2)

• Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) at different time points [Срок оценки: 3 to 6 months of treatment]
• Treatment-emergent adverse events (TEAEs) [Срок оценки: From enrollment to 8 months of study]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).
• Current liver disease, as determined by ALT or AST levels above upper limit of normal at Screening Visit.
• Chronic liver disease.
• Hemoglobin <11 g/dL, neutrophil count <1500 /µl, or platelet count <100,000 /µl.
• Known severe pulmonary fibrosis, bronchiectasis or interstitial pneumonitis.
• eGFR ≤ 40 mL/min/1.73m2 tested at Screening Visit. Kidney transplant or requires dialysis.
• Known intolerance and/or known contraindication to MTX treatment or MTX treatment considered inappropriate
• Has uncontrolled type 2 diabetes at Screening with HbA1c ≥8.5%. Patients with type 1 diabetes will be excluded.
• Has known latent autoimmune diabetes of adult.
• Immunocompromised state, regardless of etiology.
• History or treatment of malignancy in the last 5 years, excluding localized, nonmelanoma skin cancers (e.g. basal or squamous cell)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 18 центров

• Applied Research Center of Arkansas — Little Rock
• Triwest Research Associates Llc — El Cajon
• Clinical Research of West Florida, Inc. — Clearwater
• Accel Research Sites - Deland Clinical Research Unit — DeLand
• ICR Sites East — Doral
• Qway Research — Hialeah
• Bioclinical Research Alliance, Inc — Miami
• D&H National Research Centers (North Miami) — Miami
• … и ещё 10 центров

Грузия · 6 центров

• Aleksandre Aladashvili Clinic LLC, Georgia — Tbilisi
• Tbilisi Heart and Vascular Clinic Ltd , Georgia — Tbilisi
• Mediclub Georgia — Tbilisi
• Tbilisi Institute of Medicine, Georgia — Tbilisi
• Georgian-Dutch Hospital, Georgia — Tbilisi
• LTD First Medical Center, Georgia — Tbilisi

Израиль · 3 центра

• HaEmek MC, Israel — Afula
• Barzilai MC, Israel — Ashkelon
• Meir MC, Israel — Kfar Saba

Идентификаторы

NCT: NCT07280156 · PB115-GT-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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