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Systolic Heart FailurePhase 1NCT03534297

Study of Dapansutrile Capsules in Heart Failure

A Phase 1 study testing dapansutrile capsules in people with Systolic Heart Failure, run by Olatec Therapeutics, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systolic Heart Failure
What is being tested?
dapansutrile capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteUnited States
Study dates
16 May 2018to 21 Nov 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female subjects 18 years old or older
  • Symptomatic stable HF (NYHA class II-III) with reduced left ventricular ejection fraction (LVEF≤40%, measured within 6 months of enrollment - no changes in cardiac medications or new device implantation within past 2 months)
  • Peak exercise limited by shortness of breath and/or fatigue associated with a respiratory exchange ratio (RER) > 1.00 (reflecting maximal aerobic effort)
  • Reduced peak aerobic exercise capacity (peak VO2) to less than 80% of predicted value by age/gender at Baseline
  • Plasma CRP or hsCRP levels > 2 mg/L at Screening
  • Acceptable overall medical condition to be safely enrolled in and to complete the study (with specific regard to cardiovascular, renal and hepatic conditions) in the opinion of the Principal Investigator
  • Ability to provide written, informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to understand and comply with all the requirements of the study

Who cannot join

  • Women of childbearing potential, or men whose sexual partner(s) is a woman of childbearing potential who:
  • Are or intend to become pregnant (including use of fertility drugs) during the study
  • Are nursing
  • Are not using an acceptable, highly effective method of contraception until all follow-up procedures are complete. (Acceptable, highly effective forms of contraception are defined as: oral contraception, intrauterine device, systemic [injectable or patch] contraception, double barrier methods, naturally or surgically sterile, strict abstinence or partner has been sterilized. If hormonal-based birth control is being used, subject or subject's sexual partner(s) must be on a stable-dose for ≥ 3 months prior to the Baseline visit and maintained at the same dosing level throughout the study.)
  • Abnormal blood pressure or heart rate response, angina or ECG changes (ischemia or arrhythmias) occurring during CPX
  • Presence or known history of autoimmune conditions (e.g., systemic lupus erythematosus, hypophysitis, etc.)
Show all 27Show fewer
  • History or evidence of active tuberculosis (TB) infection at Baseline visit or one of the risk factors for tuberculosis such as but not limited or exclusive to:
  • History of any of the following: residence in a congregate setting (e.g., jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g., injection or non-injection), health-care workers with unprotected exposure to subjects who are at high risk of TB or subjects with TB disease before the identification and correct airborne precautions of the subject or
  • Close contact (i.e., share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours)) with a person with active pulmonary TB disease within the last 12 months.
  • Use of any prohibited concomitant medications/therapies over the periods defined in Section 5.6.3 or planned use of any prohibited concomitant medications/therapies during the Treatment Period
  • Any other concomitant medical or psychiatric condition(s), disease(s) or prior surgery(ies) that, in the opinion of the Principal Investigator, would impair the subject from safely participating in the trial and/or completing protocol requirements, including but not limited to:
  • physical inability to walk on a treadmill
  • decompensated HF (edema, NYHA IV)
  • significant ischemic heart disease, angina
  • arterial hypotension (blood pressure [BP] systolic < 90 mmHg)
  • arterial hypertension (resting BP systolic > 160 mmHg)
  • atrial fibrillation with rapid ventricular response
  • severe valvular disease
  • severe chronic obstructive or restrictive pulmonary disease
  • moderate-severe anemia (Hgb < 10 g/dL)
  • severe diabetic neuropathy or myopathy
  • Active or recent (within 2 weeks) infection prior to the Baseline visit
  • History of or known positive for HIV, Hepatitis B surface antigen or antibodies to Hepatitis C Virus
  • Known history of renal impairment and/or creatinine clearance less than 50 mL/min calculated by Cockcroft-Gault method
  • Active malignancy or recent malignancy with chemotherapy treatment within the past 6 months
  • Enrollment in any trial and/or use of any investigational product or device within the immediate 30-day period prior to the Baseline visit
  • Previous exposure to the investigational product

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Virginia Commonwealth University - Pauley Heart Center

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: A Phase 1b, Randomized, Double-Blinded, Dose Escalation, Single Center, Repeat-Dose Safety and Pharmacodynamics Study of Orally Administered Dapansutrile Capsules in Subjects With NYHA II-III Systolic Heart Failure

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.

Being tested
dapansutrile capsules, Placebo capsules
Keywords
heart failure, systolic heart failure
Medical subject headings
Heart Failure, Systolic, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dapansutrile capsulesDrug

    Also called OLT1177 capsules

    Hard opaque capsules containing 100 mg of API.

  • Placebo capsulesDrug

    Hard opaque capsules containing 0 mg of API.

Study groups in NCT03534297
Study groupRoleWhat they receive
dapansutrile capsulesExperimentalA total of 8 patients in each cohort will receive dapansutrile capsules: * Cohort 1 will receive 5x 100 mg dapansutrile capsules QD for 14 days * Cohort 2 will receive 5x 100 mg dapansutrile capsules BID for 14 days * Cohort 3 will receive 5x 100 mg dapansutrile capsules QID for 14 days
Receives: Drug: dapansutrile capsules
Placebo CapsulesPlacebo comparatorA total of 2 patients in each cohort will receive placebo capsules: * Cohort 1 will receive 5 placebo capsules QD for 14 days * Cohort 2 will receive 5 placebo capsules BID for 14 days * Cohort 3 will receive 5 placebo capsules QID for 14 days
Receives: Drug: Placebo capsules

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events

    Adverse events experienced by the patient will be recorded.

    Measured: Screening through Day 42 follow-up

Secondary outcomes (15)
  1. Cardiopulmonary exercise test

    Physician-supervised maximal aerobic exercise test will be administered using a metabolic cart that is interfaced with a motorized treadmill. Change in peak oxygen consumption in each group will be assessed.

    Measured: Day 14

  2. Transthoracic Doppler ECG - Left Ventricle Ejection Fraction

    Changes in left ventricular ejection fraction will be analyzed.

    Measured: Day 14

  3. Transthoracic Doppler ECG - Left Ventricular Filling Pressure

    Changes in estimated left ventricular filling pressure, measured as ratio of early diastolic transmitral pulsed wave Doppler flow velocity (E) to tissue Doppler velocity of the mitral annulus (e') will be analyzed.

    Measured: Day 14

  4. Bioimpedance analysis

    Bioimpedance is a non-invasive, quick and safe technique that allows to estimate body composition compartments (total body water, intracellular water, extracellular water, fat mass, fat-free mass, lean mass). Change in total body water will be assessed.

    Measured: Day 14

  5. Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score

    Change in KCCQ score, a 23-item, self-administered instrument that independently measures a patient's perception of their health status, which includes heart failure symptoms. This scale is quantified in six domains: physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Each domain is scored on a 0-100 scale with 100 being better and 0 being worse. Two summary scores are calculated: the Clinical Summary Score (mean of symptom and physical function domain scores) and the Overall Summary Score (mean of the symptom, physical function, social limitations and quality of life scores).

    Measured: Day 14

  6. Kansas City Cardiomyopathy Questionnaire - Overall Summary Score

    Change in KCCQ score, a 23-item, self-administered instrument that independently measures a patient's perception of their health status, which includes heart failure symptoms. This scale is quantified in six domains: physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Each domain is scored on a 0-100 scale with 100 being better and 0 being worse. Two summary scores are calculated: the Clinical Summary Score (mean of symptom and physical function domain scores) and the Overall Summary Score (mean of the symptom, physical function, social limitations and quality of life scores).

    Measured: Day 14

  7. Duke Activity Status Index

    Change in Duke Activity Status Index, a self-administered questionnaire that measures a patient's functional capacity. The index consists of 12 "yes or no" questions, which are summed and used to calculate VO2peak and METS.

    Measured: Day 14

  8. Vital signs - Pulse

    Changes in pulse will be analyzed.

    Measured: Day 14

  9. Vital signs - Blood Pressure

    Changes in systolic and diastolic blood pressure will be analyzed.

    Measured: Day 14

  10. Vital signs - Temperature

    Changes in body temperature will be analyzed.

    Measured: Day 14

  11. Vital signs - Respiratory Rate

    Changes in respiratory rate will be analyzed.

    Measured: Day 14

  12. Safety Laboratory Measurements - Chemistry

    Changes in blood chemistry will be analyzed.

    Measured: Day 14

  13. Safety Laboratory Measurements - Hematology

    Changes in complete blood count will be analyzed.

    Measured: Day 14

  14. Physical Examination

    A full or targeted physical examination of the patient's major body systems

    Measured: Day 14

  15. 12-lead electrocardiogram

    Electrodes will be placed on the patient to obtain a recording of the electrical activity of the heart.

    Measured: Day 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2018
  2. Study start16 May 2018
  3. Primary completion21 Nov 2019
  4. Study completion21 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects will be assigned to receive either dapansutrile capsules or placebo capsules in a 4:1 ratio within each Cohort.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03534297
Sponsor's protocol ID
OLT1177-06
Status last verified
Jan 2020
First submitted
21 Dec 2017
Last updated
9 Jan 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • de Baat A, Trinh B, Ellingsgaard H, Donath MY. Physiological role of cytokines in the regulation of mammalian metabolism. Trends Immunol. 2023 Aug;44(8):613-627. doi: 10.1016/j.it.2023.06.002. Epub 2023 Jul 7.

    PubMed 37423882
  • Wohlford GF, Van Tassell BW, Billingsley HE, Kadariya D, Canada JM, Carbone S, Mihalick VL, Bonaventura A, Vecchie A, Chiabrando JG, Bressi E, Thomas G, Ho AC, Marawan AA, Dell M, Trankle CR, Turlington J, Markley R, Abbate A. 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. J Cardiovasc Pharmacol. 2020 Oct 24;77(1):49-60. doi: 10.1097/FJC.0000000000000931.

    PubMed 33235030

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dapansutrile capsules in people with Systolic Heart Failure, run by Olatec Therapeutics, Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (time frame: Screening through Day 42 follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03534297, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020.

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