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Trial record 2 of 2 for:    NLRP3 | gout

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05658575
Recruitment Status : Recruiting
First Posted : December 20, 2022
Last Update Posted : January 23, 2023
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Acute Gout Flare Gout Attack Gout Flare Gouty Arthritis Gout Arthritis Joint Pain Drug: Dapansutrile Other: Placebo Tablet Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
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
Actual Study Start Date : January 6, 2022
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Gout
MedlinePlus related topics: Gout

Arm Intervention/treatment
Experimental: 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.
Other Name: OLT1177

Placebo Comparator: 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
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 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 [ Time Frame: 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 [ Time Frame: 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). [ Time Frame: 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) [ Time Frame: 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). [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: 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. [ Time Frame: 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 assess and compare changes in relevant circulating inflammatory biomarkers between dapansutrile and placebo. [ Time Frame: 15 days ]
    Changes in plasma levels of circulating CRP, neutrophils, and relevant inflammatory cytokines (e.g., IL-1β, IL-6).

  9. To characterize the population PK of dapansutrile and exposure-response relationship for efficacy and safety. [ Time Frame: up to 15 days ]
    Blood samples will be drawn and analyzed in order to characterize the population PK of dapansutrile

  10. Physical examinations [ Time Frame: Up to 15 days ]
    Physical examinations will be conducted to assess changes in subject health throughout the duration of the study.

  11. Vital signs [ Time Frame: 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

  12. Electrocardiograms [ Time Frame: 15 days ]
    Electrocardiograms will be captured and analyzed for changes throughout the duration of the study.

  13. Safety laboratory measurements [ Time Frame: 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

  14. Adverse events [ Time Frame: Up to 36 days ]
    Adverse events will be described with respect to seriousness, intensity, relationship to treatment, action taken and outcome of the event.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects age 18 or older
  • Clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria
  • 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 Screening/Baseline
  • Previously diagnosed subjects: Confirmation of gout diagnosis as above OR documented history of the presence of MSU crystals in synovial fluid from the target joint or bursa; OR historical imaging report of urate deposition in the target joint or bursa in medical record
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05658575


Contacts
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Contact: Mustafa Noor, MD, FACP +1 833-652-8321 ext 114 mustafa.noor@olatec.com

Locations
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United States, Alaska
Clinical Trial Site Recruiting
Anchorage, Alaska, United States, 99508
Contact: Clinical T Site         
United States, Pennsylvania
Clinical Trial Site Recruiting
Duncansville, Pennsylvania, United States, 16635
Contact: Clinic Contact         
Sponsors and Collaborators
Olatec Therapeutics LLC
Investigators
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Study Director: Mustafa Noor, MD, FACP Olatec Therapeutics LLC
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Responsible Party: Olatec Therapeutics LLC
ClinicalTrials.gov Identifier: NCT05658575    
Other Study ID Numbers: OLT1177-08
First Posted: December 20, 2022    Key Record Dates
Last Update Posted: January 23, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Olatec Therapeutics LLC:
gout
NLRP3
NLRP3 inhibitor
gouty arthritis
mono-articular arthritis
dapansutrile
OLT1177
joint pain
inflammation
gouty Inflammation
inflammasomes
IL-1 beta
IL-1 inflammation
autoinflammatory conditions
hyperuricemia
uric acid crystal
flare
small-molecule
therapeutic
Additional relevant MeSH terms:
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Gout
Arthritis
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
Dapansutrile
Anti-Inflammatory Agents