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Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

Primary Purpose

Acute Gout Flare, Gout Attack, Gout Flare

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Dapansutrile
Placebo Tablet
Sponsored by
Olatec Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Gout Flare focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapansutrile

Placebo Tablet

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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".
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.
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".
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.
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.
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.
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
Physical examinations
Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.
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
Electrocardiograms
Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.
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
Adverse events
Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.

Full Information

First Posted
November 29, 2022
Last Updated
October 11, 2023
Sponsor
Olatec Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05658575
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2023 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Olatec Therapeutics LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapansutrile
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Tablet
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Dapansutrile
Other Intervention Name(s)
OLT1177
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo Tablet
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Change in joint pain in the target joint at scheduled time points post initial loading dose of study drug
Description
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.
Time Frame
12, 24, 36, 48 and 60 hours; 8 and 15 days
Title
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).
Description
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".
Time Frame
4 and 8 days
Title
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)
Description
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.
Time Frame
8 and 15 days
Title
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).
Description
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".
Time Frame
4 and 8 days
Title
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.
Description
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.
Time Frame
48 and 72 hours; 8 and 15 days
Title
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).
Description
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.
Time Frame
15 days
Title
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.
Description
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.
Time Frame
4, 8 and 15 days
Title
To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety.
Description
Blood samples will be drawn and analyzed in order to characterize the population PK of dapansutrile
Time Frame
up to 15 days
Title
Physical examinations
Description
Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.
Time Frame
Up to 15 days
Title
Vital signs
Description
Vital signs consisting of pulse, resting blood pressure, temperature and respirations will be recorded and analyzed for changes throughout the duration of the study
Time Frame
Up to 15 days
Title
Electrocardiograms
Description
Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.
Time Frame
15 days
Title
Safety laboratory measurements
Description
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
Time Frame
Up to 15 days
Title
Adverse events
Description
Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.
Time Frame
Up to 36 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mustafa Noor, MD, FACP
Phone
+1 833-652-8321
Ext
114
Email
mustafa.noor@olatec.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mustafa Noor, MD, FACP
Organizational Affiliation
Olatec Therapeutics LLC
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Trial Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Clinical Trial Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Thomasville
State/Province
Georgia
ZIP/Postal Code
31792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinic Contact
Facility Name
Clinical Trial Site
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79124
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Bothell
State/Province
Washington
ZIP/Postal Code
98021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Facility Name
Clinical Trial Site
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Contact

12. IPD Sharing Statement

Learn more about this trial

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

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