Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Olatec Therapeutics LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

3 Oct 2023 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518844-20-00

EudraCT number

2019-002717-19

ClinicalTrials.gov

NCT05658575

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

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)

Secondary objectives 6

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 the use of and time to the first intake of any Rescue Medication and/or Escape Medication taken for non-response
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
6. Exploratory Objective: To assess and compare changes in relevant circulating inflammatory biomarkers between dapansutrile and placebo

Conditions and MedDRA coding

Treatment of Acute Gout Flare

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 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
3. 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
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 studyrelated procedures
6. 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 21

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
2. Presence of any palpable and visible tophi by physical examination
3. Has ≥ 4 joints with an acute gout flare at the Baseline Visit/Study Day 1
4. Presence of pain due to active 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 requirements
9. 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)
10. 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)
11. 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
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 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
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 Baseline Visit/Study 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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. 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
2. Subject-assessed PGART on Study Day 8
3. 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
4. Investigator-assessed IGART at scheduled assessments through Study Day 8
5. 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
6. Time to intake of medication taken for non-response, e.g., Rescue Medication and/or Escape Medication, from first IMP administration
7. 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
8. Change from baseline in the subject-assessed QoL questionnaire (SF-12v2) at scheduled assessments through Study Day 15
9. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Olatec Therapeutics LLC

Sponsor organisation

Olatec Therapeutics LLC

Address

800 5th Avenue Suite 25d

City

New York

Postcode

10065-7216

Country

United States

Scientific contact point

Organisation

Olatec Therapeutics LLC

Contact name

Vice President, Clinical Development Operations

Public contact point

Organisation

Olatec Therapeutics LLC

Contact name

Vice President, Clinical Development Operations

Third parties 5

Locations

3 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications