NCT03534297

Study of Dapansutrile Capsules in Heart Failure

Completed Phase 1 Last updated 9 January 2020

What this trial tests

Phase 1 trial testing dapansutrile capsules in Systolic Heart Failure in 30 participants. Completed in 21 November 2019.

Timeline

16 May 2018

Primary endpoint
21 November 2019

21 November 2019

Quick facts

Lead sponsor	Olatec Therapeutics LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	30
Start date	16 May 2018
Primary completion	21 November 2019
Estimated completion	21 November 2019
Sites	1 location across United States

Drugs / interventions tested

• dapansutrile capsules — full drug profile →
• Placebo capsules — full drug profile →

Conditions studied

• Systolic Heart Failure — all drugs for Systolic Heart Failure →

Sponsor

Olatec Therapeutics LLC — full company profile →

Who can join

18 and older, any sex, with Systolic Heart Failure. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase 1b randomized, double-blinded, single-center safety and pharmacodynamics study of sequential cohort, dose-escalating, repeat-dosing of dapansutrile or placebo (4:1 ratio) in subjects with stable systolic heart failure (HF) with LVEF≤40% symptomatic for NYHA functional classification II-III who show signs of systemic inflammation (high sensitivity plasma C reactive protein \[hsCRP\] \> 2 mg/L). A total of 30 subjects will be enrolled in 3 sequential cohorts by randomized allocation (8 active and 2 placebo within each cohort). Progression to cohort 2 with dose escalation will occur following the Day 28 visit of the last subject in the first cohort. Progression to cohort 3 with dose escalation will occur following the Day 8 visit of the last subject in the second cohort.

Subjects will be screened and evaluated twice for eligibility: 1) at the time of Screening (up to 28 days prior to enrollment); and 2) at the Baseline visit, prior to randomization. Following enrollment, Baseline assessments will be conducted and the first dose of investigational product (either dapansutrile capsules or placebo capsules) will be administered at the clinical site upon completion of all assessment and collection of baseline parameters. Subjects will then self-administer investigational product once, twice or four times daily, depending on cohort, for up to fourteen (14) consecutive days beginning at the Baseline visit and continuing through the planned Day 14 visit. Subjects will return to the study clinic on Days 4, 8, 14 and 28 for follow-up visits. Additionally, subjects will be contacted for telephone follow-up on Day 42.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inflammation and atherosclerosis: signaling pathways and therapeutic intervention.
   Kong P, Cui ZY, Huang XF, Zhang DD, et al · · 2022 · cited 749× · PMID 35459215 · DOI 10.1038/s41392-022-00955-7
2. Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease.
   Abbate A, Toldo S, Marchetti C, Kron J, et al · · 2020 · cited 563× · PMID 32324502 · DOI 10.1161/circresaha.120.315937
3. The role of inflammasomes in human diseases and their potential as therapeutic targets.
   Yao J, Sterling K, Wang Z, Zhang Y, et al · · 2024 · cited 135× · PMID 38177104 · DOI 10.1038/s41392-023-01687-y
4. Phase 1B, Randomized, Double-Blinded, Dose Escalation, Single-Center, Repeat Dose Safety and Pharmacodynamics Study of the Oral NLRP3 Inhibitor Dapansutrile in Subjects With NYHA II-III Systolic Heart Failure.
   Wohlford GF, Van Tassell BW, Billingsley HE, Kadariya D, et al · · 2020 · cited 121× · PMID 33235030 · DOI 10.1097/fjc.0000000000000931
5. Innate immunity as a target for acute cardioprotection.
   Zuurbier CJ, Abbate A, Cabrera-Fuentes HA, Cohen MV, et al · · 2019 · cited 112× · PMID 30576455 · DOI 10.1093/cvr/cvy304
6. Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics.
   Marchesan JT, Girnary MS, Moss K, Monaghan ET, et al · · 2020 · cited 96× · PMID 31850638 · DOI 10.1111/prd.12269
7. DC ENaC-Dependent Inflammasome Activation Contributes to Salt-Sensitive Hypertension.
   Pitzer A, Elijovich F, Laffer CL, Ertuglu LA, et al · · 2022 · cited 88× · PMID 35862128 · DOI 10.1161/circresaha.122.320818
8. Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18.
   Alehashemi S, Goldbach-Mansky R. · · 2020 · cited 78× · PMID 32983099 · DOI 10.3389/fimmu.2020.01840