Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare
- Conditions
- GoutGout FlareArthritisGout AttackAcute Gout FlareJoint PainGouty Arthritis
- Interventions
- Other: Placebo Tablet
- Registration Number
- NCT05658575
- Lead Sponsor
- Olatec Therapeutics LLC
- 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 Screening/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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Tablet 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. Dapansutrile 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.
- Primary Outcome Measures
Name Time Method 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 72 hours Change from baseline in the subject-assessed pain intensity score evaluated on a 100-mm visual analogue scale (VAS) in the target joint at 72 hours post initial loading dose for dapansutrile compared to placebo. The visual analog scale has anchors of 0 indicating no pain and 100 indicating the worst pain.
- Secondary Outcome Measures
Name Time Method Change in joint pain in the target joint at scheduled time points post initial loading dose of study drug 12, 24, 36, 48 and 60 hours; 8 and 15 days Change from baseline in the subject-assessed pain intensity score evaluated on a 100-mm visual analogue scale (VAS) in the target joint at specified timepoints up to Day 15 post initial loading dose of study drug. The visual analog scale has anchors of 0 indicating no pain and 100 indicating the worst pain.
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) 8 and 15 days Change from baseline in the Investigator-assessed Target Joint Score at scheduled assessments through Study Day 15. The Investigator-assessed Target Joint Score is a combined assessment of individual assessments for the following outcome domains: tenderness, swelling, erythema, warmth, and range of motion each with a scale of 0 through 3, with lower scoring in each domain indicating better outcomes in the respective domain.
To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety. up to 15 days Blood samples will be drawn and analyzed in order to characterize the population PK of dapansutrile
Adverse events Up to 36 days Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.
Vital signs Up to 15 days Vital signs consisting of pulse, resting blood pressure, temperature and respirations will be recorded and analyzed for changes throughout the duration of the study
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. 4, 8 and 15 days Change from baseline in the subject-assessed pain intensity score evaluated on a 100-mm visual analogue scale (VAS) in any actively flaring non-target joint(s) up to Day 15 post initial loading dose of study drug. The visual analog scale has anchors of 0 indicating no pain and 100 indicating the worst pain.
Safety laboratory measurements Up to 15 days Blood samples will be drawn and analyzed for routine chemistry blood markers, routine hematology/complete blood count and routine urinalysis will be performed throughout the duration of the study
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). 15 days Change from baseline in the subject-assessed Quality of Life (QoL) questionnaire Short Form Health Survey-12 version 2.0 (SF-12v2) at scheduled assessments through Study Day 15.
Physical examinations Up to 15 days Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.
Electrocardiograms 15 days Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.
Trial Locations
- Locations (33)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Arizona Arthritis & Rheumatology Associates - Glendale
🇺🇸Glendale, Arizona, United States
Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa
🇺🇸Mesa, Arizona, United States
American Institute of Research
🇺🇸Los Angeles, California, United States
TriWest Research Associates
🇺🇸San Diego, California, United States
Valiance Clinical Research - Tarzana
🇺🇸Tarzana, California, United States
Hillcrest Medical Research
🇺🇸DeLand, Florida, United States
University of Florida Health Jacksonville
🇺🇸Jacksonville, Florida, United States
Well Pharma Medical Research
🇺🇸Miami, Florida, United States
Clinical Research of West Florida
🇺🇸Tampa, Florida, United States
Arthritis Center of North Georgia - Gainesville
🇺🇸Gainesville, Georgia, United States
Great Lakes Clinical Trials
🇺🇸Chicago, Illinois, United States
Clinical Trial Site
🇺🇸Bothell, Washington, United States
The Research Group of Lexington
🇺🇸Lexington, Kentucky, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Montana Medical Research
🇺🇸Missoula, Montana, United States
NYU Langone
🇺🇸New York, New York, United States
IMA Clinical Research - Manhattan
🇺🇸New York, New York, United States
Altoona Research
🇺🇸Duncansville, Pennsylvania, United States
Lower Country Rheumatology - Summerville
🇺🇸Summerville, South Carolina, United States
Amarillo Center of Clinical Research
🇺🇸Amarillo, Texas, United States
Utah Health - University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
Arthritis Northwest
🇺🇸Spokane, Washington, United States
Centre Hospitalier Universitaire de Bordeaux - Hôpital Pellegrin
🇫🇷Bordeaux, France
Hôpital Saint Philibert
🇫🇷Lomme, France
Hôpital Lariboisière
🇫🇷Paris, France
CHU de Rouen - Hôpital Charles-Nicolle
🇫🇷Rouen, France
Emek Medical Center
🇮🇱Afula, Israel
Reade Research BV
🇳🇱Amsterdam, Netherlands
VieCuri Medisch Centrum
🇳🇱Venlo, Netherlands
Hospital general Universitario Dr. Balmis
🇪🇸Alicante, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain