Clinical trial NCT05658575: Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Gout Flare
Gout Attack
Gout Flare
Gouty Arthritis
Gout
Arthritis
Joint Pain
Keywords: gout
gouty arthritis
mono-articular arthritis
NLRP3
NLRP3 inhibitor
dapansutrile
OLT1177
joint pain
inflammation
gouty Inflammation
inflammasomes
IL-1 beta
IL-1 inflammation
autoinflammatory conditions
hyperuricemia
uric acid crystal
flare
small-molecule
therapeutic
Lead sponsor: Olatec Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2022-12-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: 72 hours
Secondary outcomes:
measure: Change in joint pain in the target joint at scheduled time points post initial loading dose of study drug
timeFrame: 12, 24, 36, 48 and 60 hours; 8 and 15 days
measure: 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).
timeFrame: 4 and 8 days
measure: 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)
timeFrame: 8 and 15 days
measure: 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).
timeFrame: 4 and 8 days
measure: 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.
timeFrame: 48 and 72 hours; 8 and 15 days
measure: 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).
timeFrame: 15 days
measure: 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.
timeFrame: 4, 8 and 15 days
measure: To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety.
timeFrame: up to 15 days
measure: Physical examinations
timeFrame: Up to 15 days
measure: Vital signs
timeFrame: Up to 15 days
measure: Electrocardiograms
timeFrame: 15 days
measure: Safety laboratory measurements
timeFrame: Up to 15 days
measure: Adverse events
timeFrame: Up to 36 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: Arizona Arthritis &amp; Rheumatology Associates - Glendale
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa
state: Arizona
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: San Diego
country: United States
facility: TriWest Research Associates
state: California
city: Tarzana
country: United States
facility: Valiance Clinical Research - Tarzana
state: California
city: DeLand
country: United States
facility: Hillcrest Medical Research
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Jacksonville
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Gainesville
country: United States
facility: Arthritis Center of North Georgia - Gainesville
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Orland Park
country: United States
facility: Advanced Quality Medical Research
state: Illinois
city: Lexington
country: United States
facility: The Research Group of Lexington
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: IMA Clinical Research - Manhattan
state: New York
city: Duncansville
country: United States
facility: Altoona Research
state: Pennsylvania
city: Summerville
country: United States
facility: Lower Country Rheumatology - Summerville
state: South Carolina
city: Amarillo
country: United States
facility: Amarillo Center of Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Utah Health - University of Utah Hospital
state: Utah
city: Bothell
country: United States
facility: Clinical Trial Site
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest
state: Washington
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Hôpital Pellegrin
city: Lomme
country: France
facility: Hôpital Saint Philibert
city: Paris
country: France
facility: Hôpital Lariboisière
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles-Nicolle
city: Afula
country: Israel
facility: Emek Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Petah-Tiqva
country: Israel
facility: Rabin Medical Center - Beilinson and Hasharon
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Amsterdam
country: Netherlands
facility: Reade Research BV
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum
city: Alicante
country: Spain
facility: Hospital Universitario san Juan de Alicante
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
Study officials:
References: