Dapansutrile for Gout Flares

Recruiting at 52 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Olatec Therapeutics LLC

Must not be taking: Paracetamol, Acetaminophen, others

Disqualifiers: Tophi, Rheumatoid arthritis, Kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 7 days

300 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this trial is to investigate the efficacy and safety of dapansutrile (OLT1177®) tablets in subjects with an acute gout flare.

Will I have to stop taking my current medications?

The trial protocol mentions that some medications might be prohibited during the study, but it doesn't specify which ones. You may need to stop certain medications, especially pain relievers like paracetamol/acetaminophen, close to the start of the trial. It's best to discuss your current medications with the trial team to get specific guidance.

How is the drug Dapansutrile different from other gout treatments?

Dapansutrile is unique because it is an oral medication that targets inflammation by inhibiting the NLRP3 inflammasome, a part of the immune system involved in inflammation, which is different from traditional gout treatments that primarily focus on lowering uric acid levels or using general anti-inflammatory drugs like NSAIDs. ^{1 2 3 4 5}

Research Team

Mustafa Noor, MD, FACP

Principal Investigator

Olatec Therapeutics LLC

Eligibility Criteria

This trial is for adults with a recent gout flare-up, diagnosed per specific criteria. Participants must understand the study and give consent. Excluded are those with visible tophi, allergies to the drug or similar drugs, infectious arthritis, recent COVID-19 infection, cancer treatments within a certain period, use of prohibited medications including paracetamol before baseline (except as rescue medication after day 4), other inflammatory arthritides, more than three joints with gout flares at screening or significant kidney disease.

Inclusion Criteria

I've had a gout flare-up in a joint within the last 4 days.

You have been diagnosed with gout based on specific criteria from 2015.

Provide written informed consent and understand and comply with all trial requirements

Exclusion Criteria

I don't have significant pain elsewhere that would affect my ability to judge my joint pain.

You are allergic to paracetamol/acetaminophen.

I might have an infection in my joint.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

96 hours

1 visit (in-person)

Treatment

Participants receive dapansutrile or placebo tablets with an initial loading dose followed by a twice daily maintenance dosing regimen for 7 days

7 days

3 visits (in-person) on Day 1, Day 4, and Day 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

1 visit (in-person) on Day 15

Treatment Details

Interventions

• Dapansutrile
• Placebo Tablet

Trial Overview The trial is testing Dapansutrile tablets' effectiveness and safety in treating acute gout flare-ups compared to placebo tablets. Participants will be randomly assigned to receive either the active drug or an inactive placebo without knowing which one they're getting.

Participant Groups

Group I: Dapansutrile Experimental Treatment 1 Intervention

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.

Group II: Placebo Tablet Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Olatec Therapeutics LLC

Lead Sponsor

Trials

10

Recruited

1,100+

Findings from Research

Gout treatment in patients with chronic kidney disease (CKD) stages 3-5 is complicated due to limited options and the risk of worsening kidney function, as highlighted by a review of 33 studies focusing on various treatments like colchicine and interleukin-1 inhibitors.

Most clinical trials have excluded patients with severe CKD, indicating a significant gap in understanding the efficacy and safety of gout treatments for this population, and emphasizing the need for future studies to include these patients and report outcomes based on their renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review. Pisaniello, HL., Fisher, MC., Farquhar, H., et al.[2021]

Several new therapies for gout have emerged, focusing on lowering serum urate levels and treating gout flares, with verinurad being highlighted as the most promising urate-lowering therapy.

Arhalofenate shows potential for both urate lowering and anti-inflammatory effects, but further data is needed to confirm its efficacy and safety, along with other therapies like bucillamine and those in early development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert opinion on emerging urate-lowering therapies. Stamp, LK., Merriman, TR., Singh, JA.[2018]

The management of gout involves three key stages: treating acute attacks, lowering uric acid levels to prevent future flares, and providing prophylaxis against acute attacks, with NSAIDs being the preferred treatment for acute inflammation if started early.

For chronic gout management, xanthine oxidase inhibitors like allopurinol are recommended as first-line treatments, especially for patients with renal issues or those on diuretics, while uricosuric drugs are suitable for patients allergic to allopurinol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of acute and chronic gouty arthritis: present state-of-the-art. Schlesinger, N.[2018]

Canakinumab, administered as a single dose during acute gout flares, provided rapid and effective pain relief while also suppressing future flares and inflammation in patients who cannot use NSAIDs or colchicine, based on two phase 3 studies.

In comparison to the active treatment triamcinolone acetonide, canakinumab was consistently more effective and well tolerated, making it a suitable option for patients with frequent gout attacks and multiple comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab for the Patient With Difficult-to-Treat Gouty Arthritis: Review of the Clinical Evidence. Bardin, T.[2020]

Pegloticase, a treatment for severe gout, can lower uric acid levels but may increase gout flare-ups and has only minor effects on pain and disability, based on two 6-month trials with 212 patients.

Due to serious potential side effects, including anaphylaxis and infusion reactions, probenecid is recommended as a safer alternative when allopurinol fails, while pegloticase should be avoided unless absolutely necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegloticase. An excessively dangerous and inadequately evaluated hypouricaemic drug. [2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gout flare prophylaxis and therapy use in people with chronic kidney disease: a Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)-initiated literature review. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Expert opinion on emerging urate-lowering therapies. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Management of acute and chronic gouty arthritis: present state-of-the-art. [2018]

4. France pubmed.ncbi.nlm.nih.gov

Canakinumab for the Patient With Difficult-to-Treat Gouty Arthritis: Review of the Clinical Evidence. [2020]

5. France pubmed.ncbi.nlm.nih.gov

Pegloticase. An excessively dangerous and inadequately evaluated hypouricaemic drug. [2018]