DAPANSUTRILE for Acute gout flare|Gout flare

Inclusion criteria

• {"criterion_text":"- Male and female subjects ≥ 18 years of age\n- Clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria at the Screening Visit or Baseline Visit/Study Day 1 (i.e., subject must have at least 8 points or meet Sufficient Criterion). In addition: a. Diagnosis of gout must be confirmed in the target joint at the Baseline Visit/Study Day 1 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 OR b. Documented history of gout diagnosis in the target joint or bursa; or a documented history of 2 or more gout flares in the previous 18 months\n- Confirmation of a gout flare in the target joint that began within 96 hours prior to the Baseline Visit/Study Day 1, based on the presence (at the Baseline Visit/Study Day 1) of subject-reported target joint pain at rest of ≥ 50 mm on a 0 to 100-mm VAS and at least two of the following criteria in the target joint: a. Subject-reported flare b. Subject-reported warm joint c. Subject-reported swollen joint\n- Acceptable overall medical condition to safely participate in the study and complete all study procedures (with specific regard to cardiovascular, renal, and hepatic conditions), in the opinion of the Investigator\n- Able and willing to provide written informed consent prior to initiation of any studyrelated procedures\n- Ability, in the opinion of the Investigator, to understand and comply with all the requirements of the study, which includes understanding restrictions regarding the use of Rescue Medication, Escape Medication and other prohibited medications, including other pain medications"}

Exclusion criteria

• {"criterion_text":"- Woman of childbearing potential, or man whose sexual partner(s) is a woman of childbearing potential, who: a. Is or intends to become pregnant (including use of fertility drugs) while participating in the study (through the Study Day 36 Follow-up call) b. Is lactating/breastfeeding or plans to breastfeed while participating in the study (female subjects only) c. Is not willing to use an acceptable, highly effective method of contraception until all follow-up procedures are complete\n- Use of any product containing paracetamol/acetaminophen within 4 hours prior to the Baseline Visit/Study Day 1 or planned use during the Treatment Period (with the exception of Sponsor-provided Rescue Medication [paracetamol/acetaminophen], which is permitted after completion of the target joint pain assessment on Study Day 4 (that is, ~ 72 hours after first dose)\n- Meets 2 or more of the criteria for substance use disorder provided in Appendix 1 of the protocol within 1 year of the Baseline Visit/Study Day 1\n- History of, or known positive for, human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or antibodies to hepatitis C virus (HCV) with a positive polymerase chain reaction (PCR) result for HCV\n- Known diagnosis of chronic kidney disease or known history of renal impairment (e.g., estimated glomerular filtration rate [eGFR] < 45 mL/min/1.73 m2)\n- Enrollment in an interventional trial and/or use of any investigational medicinal product or device within 90 days or five (5) half-lives of the investigational agent, whichever is longer, prior to the Screening Visit\n- Enrollment in previous gout studies with dapansutrile\n- Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, if tested, within 4 weeks of the Baseline Visit/Study Day 1\n- Active malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within the past 6 months\n- Has a serious illness that resulted in hospitalization in the 30 days preceding the Baseline Visit/Study Day 1\n- Has a hypersensitivity or allergy to dapansutrile or other drugs in its class and/or the components of the IMP (dapansutrile tablets or placebo tablets)\n- Presence of any palpable and visible tophi by physical examination\n- Has a hypersensitivity or allergy to paracetamol/acetaminophen\n- Is an employee, family member, or student of the Investigator or clinical site\n- Has ≥ 4 joints with an acute gout flare at the Baseline Visit/Study Day 1\n- Presence of pain due to active rheumatoid arthritis or other acute inflammatory arthritis\n- Evidence/suspicion of infectious/septic arthritis\n- 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, in the opinion of the Investigator\n- Known history of any clinically significant or unstable medical condition or any other disorder, condition, or circumstance (including secondary pain, or recreational or medical use of substances that may alter pain perception such as cannabidiol [CBD]- and tetrahydrocannabinol [THC]-containing substances, psilocybin, etc.) that, in the opinion of the Investigator, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments\n- Any other concomitant medical or psychiatric conditions, diseases, or prior surgeries that, in the opinion of the Investigator, would impair the subject from safely participating in the trial and/or completing protocol requirements\n- Use of any prohibited concomitant medications/therapies over the periods defined in Section 4.10.3 of 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 Baseline Visit/Study Day 1 or other pain medications within 12 hours prior to the Baseline Visit/Study Day 1)"}

Primary endpoints

• {"endpoint_text":"- The primary clinical activity outcome measurement will be: • Change from baseline in the subject-assessed pain intensity score (100-mm VAS) in the target joint at 72 hours post initial loading dose for dapansutrile compared to placebo.","definition_or_measurement_approach":"Change from baseline in subject-assessed pain intensity measured using a 100-mm visual analogue scale (VAS) in the target joint at 72 hours after the initial loading dose; comparison between dapansutrile and placebo."}

Secondary endpoints

• {"endpoint_text":"- The secondary clinical activity outcome measurements will be: • Change from baseline in the subject-assessed pain intensity score (100-mm VAS) in the target joint at 12, 24, 36, 48, and 60 hours post initial loading dose, and on Study Day 8 and Study Day 15","definition_or_measurement_approach":"Change from baseline in subject-assessed 100-mm VAS pain score at multiple timepoints (12, 24, 36, 48, 60 hours and Study Days 8 and 15) in the target joint."}
• {"endpoint_text":"- Subject-assessed PGART on Study Day 8","definition_or_measurement_approach":"Patient Global Assessment of Response to Treatment (PGART) assessed by subject on Study Day 8."}
• {"endpoint_text":"- Change from baseline in the Investigator-assessed Target Joint Score (tenderness, swelling, erythema, warmth, and range of motion) at scheduled assessments through Study Day 15","definition_or_measurement_approach":"Investigator-assessed composite target joint score (tenderness, swelling, erythema, warmth, ROM) compared to baseline at scheduled visits up to Day 15."}
• {"endpoint_text":"- Investigator-assessed IGART at scheduled assessments through Study Day 8","definition_or_measurement_approach":"Investigator Global Assessment of Response to Treatment (IGART) assessed at scheduled visits through Day 8."}
• {"endpoint_text":"- Proportion of subjects with a response (defined as a 20%, 50%, or 70% reduction from baseline without using Rescue Medication or Escape Medication) in the subject-assessed pain intensity score (100-mm VAS) in the target joint at 48 and 72 hours post initial loading dose, and on Study Day 8 and Study Day 15","definition_or_measurement_approach":"Proportion meeting predefined percent reductions (20%, 50%, 70%) from baseline in 100-mm VAS pain score in target joint at 48 and 72 hours and on Days 8 and 15, without use of rescue/escape medication."}
• {"endpoint_text":"- Time to intake of medication taken for non-response, e.g., Rescue Medication and/or Escape Medication, from first IMP administration","definition_or_measurement_approach":"Time-to-event: time from first IMP administration to first use of Rescue or Escape Medication."}
• {"endpoint_text":"- Proportion and number of subjects with Rescue Medication or Escape Medication use from the first IMP administration up to 12 hours, >12 to 24 hours, >24 to 48 hours, >48 to 72 hours, >72 hours to Day 8, and >Day 8 to Day 15","definition_or_measurement_approach":"Counts and proportions of subjects using Rescue/Escape Medication in prespecified time windows after first IMP administration."}
• {"endpoint_text":"- Change from baseline in the subject-assessed QoL questionnaire (SF-12v2) at scheduled assessments through Study Day 15","definition_or_measurement_approach":"Change from baseline in SF-12v2 quality-of-life questionnaire scores at scheduled visits through Day 15."}
• {"endpoint_text":"- Change from baseline in the subject-assessed pain intensity score (100-mm VAS) in any actively flaring non-target joint(s) on Study Day 4, Study Day 8, and Study Day 15.","definition_or_measurement_approach":"Change from baseline in 100-mm VAS pain scores for non-target joints with active flares measured on Days 4, 8 and 15."}

Methods

• Dr-to-Dr outreach letters (physician referral) as documented in recruitment materials
• Participant brochures provided to potential subjects
• Posters for public recruitment (study posters) in local languages

Netherlands

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

16-12-2025

Processing Time Days

413

Number Of Sites

4

Number Of Participants

45

Spain

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

360

Number Of Sites

5

Number Of Participants

38

France

Earliest CTIS Part Ii Submission Date

29-10-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

384

Number Of Sites

4

Number Of Participants

15

Primary sponsor

Full Name

Olatec Therapeutics LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medicover Integrated Clinical Services Sp. z o.o.

Responsibilities

Duties code 4 (as listed in sponsor thirdParties)

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

Duties codes 1,12,2,5,8 (as listed in sponsor thirdParties)

Name

Syneos Health Inc.

Responsibilities

Duties code 4 (as listed in sponsor thirdParties)

Name

Medidata Solutions Inc.

Responsibilities

Duties code 7 (data/technology services as listed)

Third parties

• {"country":"Poland","full_name":"Medicover Integrated Clinical Services Sp. z o.o.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Novasco","duties_or_roles":"Patient travel and reimbursement (code 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"sponsorDuties codes: 1, 12, 2, 5, 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}