Efficacy and Safety of Dapansutrile, Paracetamol, and Placebo in Acute Gout Flare: A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study
- Trial ID
- 2024-518844-20-00
- Protocol
- OLT1177-08
- Sponsor
- Olatec Therapeutics LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of dapansutrile as a treatment for acute gout flare, specifically in reducing joint pain at 72 hours post initial loading dose of the Investigational Medicinal Product (IMP). This is clinically relevant as effective management of joint pain is crucial in improving the quality of life for patients experiencing acute gout flares.
Secondary objectives include:
- 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.
- To assess the clinical activity of dapansutrile compared to placebo in treating signs and symptoms of an acute gout flare other than pain, such as tenderness, swelling, erythema, warmth, and range of motion.
- To assess the use of and time to the first intake of any rescue medication and/or escape medication taken for non-response.
- To characterize the population pharmacokinetics (PK) of dapansutrile and the exposure-response relationship for efficacy and safety.
- To assess the safety and tolerability of dapansutrile compared to placebo.
- Exploratory Objective: To assess and compare changes in relevant circulating inflammatory biomarkers between dapansutrile and placebo.
Participants
The clinical trial investigating the **treatment of acute gout flare** involves a total of 202 participants. The study population comprises both male and female subjects aged 18 years and older. Participants were selected based on a clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria, with confirmation of a gout flare in the target joint that began within 96 hours prior to the Baseline Visit. The trial does not include a vulnerable population, and all participants are required to have an acceptable overall medical condition to safely participate in the study, particularly concerning cardiovascular, renal, and hepatic health. Lifestyle considerations such as diet, physical activity, or habits are not specified in the trial data. The selection process ensures that participants are able and willing to provide written informed consent and comply with study requirements, including restrictions on certain medications.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **dapansutrile** tablets in subjects experiencing an acute gout flare. The trial is structured in a parallel group format and is categorized as a Phase II/III study. The primary objective is to assess the reduction in joint pain at 72 hours post-initial loading dose of the investigational medicinal product compared to placebo. The trial is expected to commence recruitment on January 1, 2024, and conclude by September 30, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, clinical diagnosis of gout, and recent onset of a gout flare. Following successful screening, participants will be randomized to receive either dapansutrile or placebo. The study involves multiple follow-up visits to monitor efficacy and safety, with assessments scheduled at 12, 24, 36, 48, 60, 72 hours, and on Study Days 8 and 15. The end-of-study visit will mark the completion of the trial for each participant.
The expected duration of participant involvement is approximately 15 days, with conditions for early termination including adverse events, non-compliance with study procedures, or withdrawal of consent. The primary endpoint is the change in pain intensity score in the target joint at 72 hours, while secondary endpoints include additional pain assessments, quality of life measures, and the use of rescue medication. The trial will ensure rigorous monitoring to maintain the integrity of the double-blind design and adherence to ethical standards throughout the study period.
Treatment
The clinical trial involves the administration of **Dapansutrile**, an investigational medicinal product, in the form of a tablet. Dapansutrile is chemically synthesized and is provided by OLATEC THERAPEUTICS LLC. The active substance in this product is dapansutrile, with a European substance number of SUB223582. The pharmaceutical form is a tablet, and the route of administration is oral. The maximum daily dose is 3000 mg, with a total maximum dose of 15000 mg over the treatment period. The dosing schedule is designed to evaluate the efficacy of dapansutrile in reducing joint pain in subjects experiencing an acute gout flare.
In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the dapansutrile tablet in appearance and is administered orally. The placebo serves as a control to assess the efficacy of the investigational product by providing a baseline for comparison.
**Paracetamol** is included as an auxiliary treatment in the study. It is provided in the form of 500 mg tablets, manufactured by HEALTHYPHARM B.V. The active substance is paracetamol, with an ATC code of N02BE01. The maximum daily dose of paracetamol is 3000 mg, with a total maximum dose of 12000 mg over a four-day treatment period. The administration route is oral, and the product is used to manage pain as part of the standard-of-care therapy for participants.
Efficacy
The efficacy of dapansutrile in treating acute gout flare will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the subject-assessed pain intensity score using a 100-mm Visual Analog Scale (VAS) in the target joint at 72 hours post initial loading dose, comparing dapansutrile to placebo. Secondary endpoints include changes from baseline in the subject-assessed pain intensity score at various timepoints: 12, 24, 36, 48, and 60 hours post initial loading dose, as well as on Study Day 8 and Study Day 15. Additionally, the subject-assessed Patient Global Assessment of Response to Therapy (PGART) will be evaluated on Study Day 8.
Further secondary endpoints involve the Investigator-assessed Target Joint Score, which includes parameters such as tenderness, swelling, erythema, warmth, and range of motion, assessed through Study Day 15. The Investigator-assessed Investigator Global Assessment of Response to Therapy (IGART) will be measured through Study Day 8. The proportion of subjects achieving a response, defined as a 20%, 50%, or 70% reduction from baseline in the subject-assessed pain intensity score without using Rescue or Escape Medication, will be evaluated at 48 and 72 hours post initial loading dose, and on Study Day 8 and Study Day 15.
Additional assessments include the time to intake of Rescue or Escape Medication from the first administration of the Investigational Medicinal Product (IMP), and the proportion and number of subjects using such medications at specified intervals. Changes from baseline in the subject-assessed Quality of Life (QoL) questionnaire (SF-12v2) and pain intensity scores in any actively flaring non-target joints will also be measured at scheduled assessments through Study Day 15.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female subjects ≥ 18 years of age
- 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
- 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
- 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
- Able and willing to provide written informed consent prior to initiation of any studyrelated procedures
- 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
- 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
- Presence of any palpable and visible tophi by physical examination
- Has ≥ 4 joints with an acute gout flare at the Baseline Visit/Study Day 1
- Presence of pain due to active 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, in the opinion of the Investigator
- 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
- 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
- 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)
- 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)
- 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
- 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
- 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)
- 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
- Enrollment in previous gout studies with dapansutrile
- 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
- Active malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within the past 6 months
- Has a serious illness that resulted in hospitalization in the 30 days preceding the Baseline Visit/Study Day 1
- 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)
- Has a hypersensitivity or allergy to paracetamol/acetaminophen
- Is an employee, family member, or student of the Investigator or clinical site
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Jan 2024 | 15 |
 The Netherlands | Recruiting | 01 Jan 2024 | — |
 Spain | Recruiting | 01 Jan 2024 | 38 |
| Netherlands | — | — | 45 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Paracetamol HTP 500 mg, tabletten | Other | TABLETTEN | ORAL USE | 3000 | 4 | PRD515505 |
Dapansutrile | Test | TABLET | ORAL USE | 3000 | 1 | PRD10857736 |
Placebo to match | Placebo | N/A | — | — | — | N/A |