Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

Arthritis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05658575
• Other study ID #: OLT1177-08
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: January 6, 2023
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Olatec Therapeutics LLC
• Contact: Mustafa Noor, MD, FACP
• Phone: +1 833-652-8321
• Email: mustafa.noor[@]olatec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Gout Flare
• Arthralgia
• Arthritis
• Arthritis, Gouty
• Gout
• Gout Attack
• Gout Flare
• Gouty Arthritis
• Joint Pain

Intervention

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.

Other:
• 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.

Locations

Country	Name	City	State
France	Hôpital Lariboisière	Paris
France	CHU de Rouen - Hôpital Charles-Nicolle	Rouen
Spain	Hospital general Universitario Dr. Balmis	Alicante
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Infanta Leonor	Madrid
United States	Amarillo Center of Clinical Research	Amarillo	Texas
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Clinical Trial Site	Bothell	Washington
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Omega Research	DeBary	Florida
United States	Hillcrest Medical Research	DeLand	Florida
United States	Altoona Research	Duncansville	Pennsylvania
United States	Arthritis Center of North Georgia - Gainesville	Gainesville	Georgia
United States	Arizona Arthritis & Rheumatology Associates - Glendale	Glendale	Arizona
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	The Research Group of Lexington	Lexington	Kentucky
United States	American Institute of Research	Los Angeles	California
United States	Arizona Arthritis & Rheumatology Associates (AARA), P.C. - Mesa	Mesa	Arizona
United States	Well Pharma Medical Research	Miami	Florida
United States	Montana Medical Research	Missoula	Montana
United States	IMA Clinical Research - Manhattan	New York	New York
United States	NYU Langone	New York	New York
United States	Clinical Trial Site	Orland Park	Illinois
United States	Utah Health - University of Utah Hospital	Salt Lake City	Utah
United States	TriWest Research Associates	San Diego	California
United States	Arthritis Northwest	Spokane	Washington
United States	Lower Country Rheumatology - Summerville	Summerville	South Carolina
United States	Clinical Research of West Florida	Tampa	Florida
United States	Valiance Clinical Research - Tarzana	Tarzana	California
United States	Clinical Trial Site	Thomasville	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Olatec Therapeutics LLC

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	72 hours
Secondary	Change in joint pain in the target joint at scheduled time points post initial loading dose of study drug	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.	12, 24, 36, 48 and 60 hours; 8 and 15 days
Secondary	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).	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".	4 and 8 days
Secondary	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)	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.	8 and 15 days
Secondary	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).	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".	4 and 8 days
Secondary	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.	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.	48 and 72 hours; 8 and 15 days
Secondary	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).	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.	15 days
Secondary	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.	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.	4, 8 and 15 days
Secondary	To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety.	Blood samples will be drawn and analyzed in order to characterize the population PK of dapansutrile	up to 15 days
Secondary	Physical examinations	Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.	Up to 15 days
Secondary	Vital signs	Vital signs consisting of pulse, resting blood pressure, temperature and respirations will be recorded and analyzed for changes throughout the duration of the study	Up to 15 days
Secondary	Electrocardiograms	Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.	15 days
Secondary	Safety laboratory measurements	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	Up to 15 days
Secondary	Adverse events	Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.	Up to 36 days