Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

Официальное название

A Multi-Center Phase 2/3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Safety and Efficacy Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

Обзор

The purpose of this trial is to investigate the efficacy and safety of dapansutrile (OLT1177®) tablets in subjects with an acute gout flare.

Подробное описание

This is a multi-center Phase 2/3 randomized, double-blind, placebo-controlled, parallel-group safety and efficacy study of dapansutrile (OLT1177®), a specific NLRP3 inhibitor, conducted in subjects with acute gout flare. Up to 300 eligible subjects will be randomized 2:1 to one of two treatment arms to receive either dapansutrile tablets or matching placebo twice daily for 7 days. An initial loading dose on Study Day 1 will be followed by a twice daily maintenance dosing regimen.

Subjects presenting with acute gout flare that began within 96 hours prior to the Baseline/Day 1 visit will be evaluated for eligibility. Subjects who are determined to be eligible will be randomized into either an active treatment arm (2/3 of the subjects enrolled) or the placebo arm (1/3 of the subjects enrolled).

Eligible subjects who are randomized into the study will also be provided with rescue medication at the Baseline/Day 1 Visit. No other pain medications, anti-inflammatory drugs (e.g., steroids or nonsteroidal anti-inflammatory drugs), or treatments for gout flare are allowed during the Treatment Period.

During the Treatment Period, subjects will return to the clinic trial site on Day 4 and, following the 7-day Treatment Period, subjects will return to the clinical trial site on Day 8, and then Day 15 with safety data collected through Day 36.

Вмешательства

• Препарат Dapansutrile
  An initial loading dose of 2000 mg dapansutrile on Day 1 followed by a maintenance regimen of 1000 mg dapansutrile twice daily starting 12 hours later through the second dose on Day 7, inclusive.
• Другое Placebo Tablet
  An initial loading dose of matching placebo (to mimic dapansutrile dosing) on Day 1 followed by a maintenance regimen of matching placebo twice daily starting 12 hours later through the second dose on Day 7, inclusive.

Первичные конечные точки

• To evaluate the efficacy of dapansutrile as an acute gout flare treatment compared to placebo in reducing joint pain at 72 hours post initial loading dose of IMP [Срок оценки: 72 hours]

Вторичные конечные точки (12)

• Change in joint pain in the target joint at scheduled time points post initial loading dose of study drug [Срок оценки: 12, 24, 36, 48 and 60 hours; 8 and 15 days]
• To assess the clinical activity of dapansutrile compared to placebo in treating signs and symptoms of an acute gout flare other than pain (tenderness, swelling, erythema, warmth, and range of motion). [Срок оценки: 4 and 8 days]
• To assess the clinical activity of dapansutrile compared to placebo in treating signs and symptoms of an acute gout flare other than pain (tenderness, swelling, erythema, warmth, and range of motion) [Срок оценки: 8 and 15 days]
• To assess the clinical activity of dapansutrile compared to placebo in treating signs and symptoms of an acute gout flare other than pain (tenderness, swelling, erythema, warmth, and range of motion). [Срок оценки: 4 and 8 days]
• To further assess the clinical activity of dapansutrile compared to placebo in reducing joint pain at scheduled time points post initial loading dose of IMP. [Срок оценки: 48 and 72 hours; 8 and 15 days]
• To assess the clinical activity of dapansutrile compared to placebo in treating signs and symptoms of an acute gout flare other than pain (tenderness, swelling, erythema, warmth, and range of motion). [Срок оценки: 15 days]
• To further assess the clinical activity of dapansutrile compared to placebo in reducing joint pain at scheduled time points post initial loading dose of IMP. [Срок оценки: 4, 8 and 15 days]
• To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety. [Срок оценки: up to 15 days]
• Physical examinations [Срок оценки: Up to 15 days]
• Vital signs [Срок оценки: Up to 15 days]
• Electrocardiograms [Срок оценки: 15 days]
• Safety laboratory measurements [Срок оценки: Up to 15 days]

Критерии участия

Критерии включения

• Male and female subjects age 18 or older
• Clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria:

A) Diagnosis of gout must be confirmed in the target joint as indicated by either the presence of monosodium urate (MSU) crystals by microscopic evaluation of synovial fluid from the target joint or bursa OR by imaging evidence of urate deposition in the target joint or bursa at the Screening/Baseline Visit/Study Day 1, or

B) Documented history in the target joint or bursa ; or documented history of 2 or more gout flares in the previous 18 months

• Confirmation of a gout flare in the target joint that began within 96 hours prior to the Screening/Baseline Visit
• Provide written informed consent and understand and comply with all trial requirements

Критерии исключения

• Presence of any palpable and visible tophi by physical examination
• Has ≥ 4 joints with an acute gout flare at Screening/Baseline
• Presence of active rheumatoid arthritis or other acute inflammatory arthritis
• Evidence/suspicion of infectious/septic arthritis
• Clinically significant general pain or non-gout-related joint pain that would interfere with the subject's ability to accurately assess pain in the target joint
• Known diagnosis of chronic kidney disease or known history of renal impairment
• Positive test for severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infection, if tested, within 4 weeks of the Screening/Baseline
• Active malignancy or recent malignancy with any systemic anti-cancer treatment
• Has a hypersensitivity or allergy to OLT1177® or other drugs in its class
• Hypersensitivity or allergy to paracetamol/acetaminophen
• Use of any prohibited concomitant medications/therapies over the periods defined in the protocol or planned use of any prohibited concomitant medications/therapies during the Treatment Period (including the use of paracetamol/acetaminophen within 4 hours prior to the Screening/Baseline Visit or other pain medications within 12 hours prior to the Screening/ Baseline Visit
• Use of any product containing paracetamol/acetaminophen within 4 hours prior to the Screening/Baseline Visit or planned use during the Treatment Period (with the exception of study-provided Rescue Medication \[paracetamol/acetaminophen\], which is permitted after completion of the first target joint pain assessment on Study Day 4

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

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 25 центров

• University of Alabama at Birmingham — Birmingham
• Arizona Arthritis & Rheumatology Associates - Glendale — Glendale
• Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa — Mesa
• American Institute of Research — Los Angeles
• TriWest Research Associates — San Diego
• Valiance Clinical Research - Tarzana — Tarzana
• Hillcrest Medical Research — DeLand
• SIMEDHealth — Gainesville
• … и ещё 17 центров

Франция · 4 центра

• Centre Hospitalier Universitaire de Bordeaux - Hôpital Pellegrin — Bordeaux
• Hôpital Saint Philibert — Lomme
• Hôpital Lariboisière — Paris
• CHU de Rouen - Hôpital Charles-Nicolle — Rouen

Израиль · 4 центра

• Emek Medical Center — Afula
• Carmel Medical Center — Haifa
• Rabin Medical Center - Beilinson and Hasharon — Petah Tikva
• The Chaim Sheba Medical Center — Ramat Gan

Испания · 4 центра

• Hospital Universitario san Juan de Alicante — Alicante
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Universitario de La Princesa — Madrid
• Hospital Universitario Infanta Leonor — Madrid

Нидерланды · 3 центра

• Reade Research BV — Amsterdam
• Maastricht Universitair Medisch Centrum — Maastricht
• VieCuri Medisch Centrum — Venlo

Идентификаторы

NCT: NCT05658575 · OLT1177-08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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