E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Acute Gout Flare |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of Acute Gout Flare |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064900 |
E.1.2 | Term | Gout flare |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 Investigational Medicinal Product (IMP) |
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E.2.2 | Secondary objectives of the trial |
1. 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
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)
3. To assess and compare changes in relevant circulating inflammatory biomarkers between dapansutrile and placebo
4. To characterize the population pharmacokinetics (PK) of dapansutrile and exposure response relationship for efficacy and safety
5. To assess the safety and tolerability of dapansutrile compared to placebo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male and female subjects ≥ 18 years of age 2) Clinical diagnosis of gout according to the 2015 ACR/EULAR Gout Classification Criteria at the Screening/Baseline Visit/Study Day 1 a. 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 b. Previously diagnosed subjects: Confirmation of gout diagnosis as per criterion 2a; 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 their medical record 3) Confirmation of a gout flare in the target joint that began within 96 hours prior to the Screening/Baseline Visit/Study Day 1, based on the presence (at the Screening/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 4) 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 5) Able and willing to provide written informed consent prior to initiation of any study related procedures 6) Ability, in the opinion of the Investigator, to understand and comply with all the requirements of the study, which includes abstaining from the use of Rescue Medication until completion of the first target joint pain assessment on Study Day 4 and abstaining from the use of other prohibited medications, including other pain medications
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E.4 | Principal exclusion criteria |
1) 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 (see Section 4.10.2 for more details on acceptable forms of contraceptives) 2) Presence of any palpable and visible tophi by physical examination 3) Has ≥ 4 joints with an acute gout flare at the Screening/Baseline Visit/Study Day 1 4) Presence of rheumatoid arthritis or other acute inflammatory arthritis 5) Evidence/suspicion of infectious/septic arthritis 6) 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 7) 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 8) 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 requirements6 9) Use of any prohibited concomitant medications/therapies over the periods defined in Section 4.10.3 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/Study Day 1 or other pain medications within 12 hours prior to the Screening/Baseline Visit/Study Day 1) 10) Use of any product containing paracetamol/acetaminophen within 4 hours prior to the Screening/Baseline Visit/Study Day 1 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) 11) Meets 2 or more of the criteria for substance use disorder provided in Appendix 1 within 1 year of the Screening/Baseline Visit/Study Day 1 12) 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 13) 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) 14) Enrollment in any trial and/or use of any investigational medicinal product or device within the immediate 1-year period prior to the Screening/Baseline Visit/Study Day 1 15) Enrollment in previous gout studies with dapansutrile 16) Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, if tested, within 4 weeks of the Screening/Baseline Visit/Day 1 17) Active malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within the past 6 months 18) Has a serious illness that resulted in hospitalization in the 30 days preceding the Screening/Baseline Visit/Study Day 1 19) 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) 20) Has a hypersensitivity or allergy to paracetamol/acetaminophen 21) Is an employee, family member, or student of the Investigator or clinical site
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 72 hours post initial loading dose |
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E.5.2 | Secondary end point(s) |
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 • Subject-assessed PGART on Study Day 8 • 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 • Investigator-assessed IGART at scheduled assessments through Study Day 8 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Refer to protocol end point timepoints |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Netherlands |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |