Dapansutrile for Gout Flares
Recruiting in Palo Alto (17 mi)
+52 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Olatec Therapeutics LLC
Must not be taking: Paracetamol, Acetaminophen, others
Disqualifiers: Tophi, Rheumatoid arthritis, Kidney disease, others
Prior Safety Data
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.
12345Eligibility 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
+1 more
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.
+9 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DapansutrileExperimental Treatment1 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 TabletPlacebo Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Omega ResearchDeBary, FL
Clinical Research of West FloridaTampa, FL
TriWest Research AssociatesSan Diego, CA
Hillcrest Medical ResearchDeLand, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Olatec Therapeutics LLCLead Sponsor
References
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]Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3-5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) < 60 ml/min/1.73 m2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed-colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification-colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of < 30 mL/min/1.73 m2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.
Expert opinion on emerging urate-lowering therapies. [2018]There has been a resurgence in gout therapeutics in the last decade, not only for the management of gout flares, but also for the treatment of hyperuricemia. This editorial summarizes new, emerging therapies for people with gout. Areas covered: We review several new therapies for gout, including those that are focused on lowering serum urate (levotofisopam, ulodesine, verinurad, merbarone, KUX-1151, UR-1102, FYU-981, SEL-212), or treating gout flares (canakinumab, bucillamine) or both (arhalofenate, diacerein). Expert opinion: Among therapies with both urate lowering and anti-inflammatory action, arhalofenate seems promising, but more data are needed. Examining therapies aimed at treating gout flares [anti-inflammatory action], bucillamine has some potential, but more data and Phase III studies are needed, to better understand its efficacy and safety. Among the urate-lowering therapies (ULTs), verinurad seems to be the most promising, while levotofisopam and ulodesine require more data. A uricase-replacement therapy with improved immune reaction (SLE-212) is in a Phase II trial. A number of ULTs including KUX-1151, UR-1102 and FYU-981 are in early development and more will be known once initial data and studies are published.
Management of acute and chronic gouty arthritis: present state-of-the-art. [2018]There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis. During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin. Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy. The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.
Canakinumab for the Patient With Difficult-to-Treat Gouty Arthritis: Review of the Clinical Evidence. [2020]Many patients with gouty arthritis experience frequent flares and have comorbidities that may limit their anti-inflammatory treatment options for acute flare management. For patients with contraindications to both NSAIDs and/or colchicine, treatment options are particularly limited, and there is an unmet medical need in this subgroup of patients. Two phase 3 studies and their extensions have demonstrated that a single dose of canakinumab during an acute flare provided rapid and effective pain relief and prolonged suppression of flares and inflammation in patients with a history of frequent flares and contraindicated for, intolerant of, or unresponsive to NSAIDs and/or colchicine. Canakinumab was consistently superior to the active comparator triamcinolone acetonide and was generally well tolerated in this patient population with a high prevalence of multiple medical comorbidities. Canakinumab should therefore be considered as a treatment option in a target population of patients with frequent gouty arthritis attacks who are unable to use NSAIDs and colchicine and in whom frequent use of corticosteroids is not considered appropriate.
Pegloticase. An excessively dangerous and inadequately evaluated hypouricaemic drug. [2018]When severe gout with tophi persists despite treatment with allopurinol, a xanthine oxidase inhibitor, the hypouricaemic drug of choice is probenecid, a uricosuric agent, in the absence of a better alternative. Pegloticase is a pegylated recombinant uricase. This enzyme catabolises uric acid into allantoin, a water-soluble substance that is excreted by the kidneys. Pegloticase has been granted EU marketing authorisation in patients who continue to have severe gout attacks despite treatment with a xanthine oxidase inhibitor such as allopurinol. Pegloticase has not been compared with probenecid nor has it been evaluated in patients who have no other treatment options. Two double-blind, randomised, placebo-controlled trials have been conducted. They lasted only 6 months and involved 212 patients in whom allopurino/therapy had failed, usually because of serious adverse effects. Pegloticase lowered uric acid levels but increased the frequency of gout flares early during treatment. At best, it had only a minor symptomatic effect on pain and disability. Its long-term effects are unknown. About 10% of patients had a serious adverse effect attributed to pegloticase, including reactions during the infusion, anaphylactic reactions, and skin infections. Thrombocytopenia and severe cardiac adverse effects are other probable adverse effects. About 90% of patients treated with pegloticase developed anti-pegloticase antibodies. Given the limited short-term symptomatic efficacy and the absence of comparative long-term evaluation, patients should not be exposed to the potentially serious adverse effects of pegloticase. Probenecid is a better choice when allopurinol is ineffective or poorly tolerated. Currently, patients with no remaining therapeutic options should simply continue to receive symptomatic treatment of gout attacks.