Study 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.

Condition or Disease	Intervention/Treatment
Acute Gout Flare Gout Attack Gout Flare Gouty Arthritis Gout Arthritis Joint Pain	Drug: Dapansutrile Other: Placebo Tablet

Study Design

Study Type	Interventional
Anticipated Enrollment	300 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Double
Primary Purpose	Treatment
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 Start Date	January 6, 2023
Anticipated Primary Completion Date	September 1, 2025
Anticipated Study Completion Date	October 1, 2025

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
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.	Drug: 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.
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.	Other: Placebo Tablet

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.
2. 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). [4 and 8 days]
   Patient Global Assessment of Response to Treatment (PGART) will be completed by the subject through Day 8. The PGART is a 5-level Likert-type single item (i.e., one general question the Subject is asked to answer) about the overall perceived status of their response to treatment on a scale from "None" to "Excellent".
3. 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.
4. 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). [4 and 8 days]
   Investigator Global Assessment of Response to Treatment (IGART) will be completed by the Investigator through Study Day 8. The IGART is a 5-level Likert-type single item (i.e., one general question the Investigator is asked to answer) about the overall perceived status of the subject's response to treatment on a scale from "None" to "Excellent".
5. 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. [48 and 72 hours; 8 and 15 days]
   Proportion of subjects with a response (defined as a 20%, 50%, or 70% reduction from baseline without using Rescue Medication) in the subject-assessed pain intensity score (100-mm VAS) in the target joint up to Day 15 post initial loading dose of study drug.
6. 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.
7. 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.
8. 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
9. Physical examinations [Up to 15 days]
   Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.
10. 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
11. Electrocardiograms [15 days]
    Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.
12. 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
13. 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.

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	Male and female subjects age 18 or older Clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria: A) For newly presenting subjects: 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) For previously diagnosed subjects: Confirmation of gout diagnosis as per criterion 2a OR history of gout diagnosis per one of the following: a. Documented history of the presence of MSU crystals in synovial fluid from the target joint or bursa ; or b. Historical imaging report of urate deposition in the target joint or bursa in their medical record5; or c. 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 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

Contacts and Locations

Sponsors and Collaborators	Olatec Therapeutics LLC
Locations	University of Alabama at Birmingham | Birmingham, Alabama, United States, 35294 Arizona Arthritis & Rheumatology Associates - Glendale | Glendale, Arizona, United States, 85306 Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa | Mesa, Arizona, United States, 85210 American Institute of Research | Los Angeles, California, United States, 90017 TriWest Research Associates | San Diego, California, United States, 92108 Valiance Clinical Research - Tarzana | Tarzana, California, United States, 91356 Omega Research | DeBary, Florida, United States, 32713 Hillcrest Medical Research | DeLand, Florida, United States, 32720 University of Florida Health Jacksonville | Jacksonville, Florida, United States, 32256 Well Pharma Medical Research | Miami, Florida, United States, 33173 Clinical Research of West Florida | Tampa, Florida, United States, 33765 Arthritis Center of North Georgia - Gainesville | Gainesville, Georgia, United States, 30501 Great Lakes Clinical Trials | Chicago, Illinois, United States, 60640 Clinical Trial Site | Orland Park, Illinois, United States, 60462 The Research Group of Lexington | Lexington, Kentucky, United States, 40503 University of Michigan | Ann Arbor, Michigan, United States, 48109 Montana Medical Research | Missoula, Montana, United States, 59808 NYU Langone | New York, New York, United States, 10016 IMA Clinical Research - Manhattan | New York, New York, United States, 10036 Altoona Research | Duncansville, Pennsylvania, United States, 16635 Lower Country Rheumatology - Summerville | Summerville, South Carolina, United States, 29486 Amarillo Center of Clinical Research | Amarillo, Texas, United States, 79124 Utah Health - University of Utah Hospital | Salt Lake City, Utah, United States, 84108 Clinical Trial Site | Bothell, Washington, United States, 98021 Arthritis Northwest | Spokane, Washington, United States, 99204 Centre Hospitalier Universitaire de Bordeaux - Hôpital Pellegrin | Bordeaux, France, 33076 Hôpital Saint Philibert | Lomme, France, 59462 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, 03010 Hospital de la Santa Creu i Sant Pau | Barcelona, Spain, 08025 Hospital Universitario Infanta Leonor | Madrid, Spain, 28031
Investigators

More Information

Additional Relevant MeSH Terms

• Arthritis
• Gout
• Arthralgia
• Arthritis, Gouty
• Joint Diseases
• Musculoskeletal Diseases
• Crystal Arthropathies
• Rheumatic Diseases
• Purine-Pyrimidine Metabolism, Inborn Errors
• Metabolism, Inborn Errors
• Genetic Diseases, Inborn
• Metabolic Diseases
• Pain
• Neurologic Manifestations