COVID-19 Cytokine Release Syndrome
Conditions
Interventions
2 treatment arms will be used in this study. Subjects will be randomly to a
treatment arm with a 1:1 ratio.
The study medication and placebo are delivered as capsules and have the same
appearance.
T
Sponsors
Olatec Therapeutics LLC
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1) Male and female subjects * 18 years of age; 2) SARS-CoV-2-positive, confirmed by Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-authorized COVID-19 test * 7 days prior to randomization; 3) Less than or equal to 7 days from first symptom onset to randomization; 4) Subjects with moderate COVID-19 consistent with the definition of *moderate* as set forth by the February 2021 FDA Guidance for Industry: COVID-19: Developing Drugs and Biological Products for Treatment or Prevention (FDA, 2021) who at the Screening/Baseline/Day 1 Visit: a. have felt feverish within the past 24 hours, b. have an SpO2 > 93% on room air at sea level6 when sitting, and c. meet at least one of the following criteria: i. Respiratory rate: * 20 breaths/minute, when the subject is sitting, ii. SpO2: * 96% on room air at sea level6, when the subject is sitting, iii. Shortness of breath: with exertion, not requiring oxygen, or iv. Heart rate: * 90 beats/minute, when the subject is sitting; 5) If all of the criteria in Inclusion 4c are met, subject must possess at least one of the following high-risk conditions known to have an underlying increased level of cytokine production; otherwise, at least two of these high-risk conditions must be met: a. 70 years or more of age, b. Obesity (body mass index [BMI] * 30 kg/m2), c. Diabetes (type 1 or 2), d. Uncontrolled hypertension, defined as diastolic > 100 mm Hg and/or systolic > 150 mm Hg without any current anti-hypertensive medications. At the time of screening if the subject is on anti-hypertensive medication(s) and diastolic or systolic rates are elevated, subject may be enrolled after consultation with the Medical Monitor, e. Known respiratory disease (including asthma or chronic obstructive pulmonary disease [COPD]), f. Known heart failure (note: subjects with New York Heart Association Class IV congestive heart failure cannot be enrolled per Exclusion Criterion 4), or g. Known coronary disease; 6) Plasma CRP level must be collected at Screening/Baseline/Day 1 Visit; 7) Acceptable overall medical condition to be safely enrolled in and complete the study in the opinion of the Investigator; 8) Ability to provide written, informed consent prior to initiation of any study-related procedures, and ability in the opinion of the Investigator to understand and comply with all the requirements of the study, which includes abstaining from the use of prohibited medications. 9) Subject must present with at least moderate symptomatology, based on having symptoms in the prior 24 hours that were uncomfortable and interfered with daily activities or required treatment other than study drug and having at least one of the following symptoms: cough; fatigue; myalgia; diarrhea; vomiting; nausea; headache; sore throat; nasal congestion; rhinorrhea; loss of taste; loss of smell; fainting; or chills, shivering, and/or sweating.
Exclusion criteria
Exclusion criteria: Main Criteria for Exclusion: 1) Women of childbearing potential, or men whose sexual partner(s) is a woman of childbearing potential, who: a. Are or intend to become pregnant (including use of fertility drugs) during the study; b. Are nursing (female subjects only); c. Are not using an acceptable, highly effective method of contraception until all follow-up procedures are complete. 2) Evidence of pre-existing or new-onset organ failure (with the exception of those conditions required for enrollment per Inclusion Criterion 5); 3) Evidence of moderate concurrent nervous system, renal, endocrine, or gastrointestinal disease, unrelated to COVID-19 as determined by the Investigator (with the exception of those conditions required for enrollment per Inclusion Criterion 5); 4) Evidence of cardiovascular disease with significant arrhythmia, congestive heart failure (New York Heart Association Class IV), unstable angina, cor pulmonale, or symptomatic pericardial effusion, not related to COVID-19 as determined by the Investigator (with the exception of those conditions required for enrollment per Inclusion Criterion 5); 5) Required use of vasoactive drug support; 6) History of myocardial infarction in the 6 months prior to the Screening/Baseline/Day 1 Visit; 7) Evidence of current liver disease, not related to COVID-19 as determined by the investigator; 8) History or evidence of active tuberculosis (TB) infection at Screening/Baseline/Day 1 Visit or one of the risk factors for tuberculosis such as but not limited or exclusive to: a. 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 b. 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. 9) History of or currently active primary or secondary immunodeficiency; 10) Past or present requirement for oxygen (e.g., nasal cannula, proning, mechanical ventilation and/or supplemental oxygen); 11) Use of any prohibited concomitant medications/therapies or planned use of any concomitant medications/therapies during the Treatment Period, including specifically: a. use of ibuprofen or diclofenac b. use of colchicine c. use of systemic steroids within 30 days of randomization d. use of janus kinase (JAK) inhibitors e. use of off-label agents (e.g., hydroxychloroquine, remdesivir, dexamethasone) and biologic and oral anti-cytokine agents (e.g., current treatment with adalimumab, infliximab, etanercept, golimumab, certolizumab pegol, tocilizumab, sarilumab, anakinra, canakinumab, rilonacept, baricitinib, tofacitinib, or upadacitinib); 12) Known history of renal impairment (e.g., calculated glomerular filtration rate [GFR] < 45 mL/min); 13) Evidence of malignant disease, or malignancies diagnosed within the previous 5 years (except for local basal or squamous cell carcinoma of the skin or carcinoma in situ of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy-related endpoint will be to compare the dapansutrile and placebo arms by the following measure: Clinical deterioration, or lack of improvement, by Day 15, defined as either having any COVID-19-related hospitalization after enrollment OR meeting both criteria of (1) worsening or persistence of shortness of breath AND (2) oxygen saturation less than 92% on room air at sea level or need for supplemental oxygen to achieve oxygen saturation of 92% or greater . Note: If the PI has chosen to treat the subject for COVID-19 on an in-patient basis (e.g., the subject is elderly or frail), hospitalization is not considered clinical deterioration unless the other criteria have been met or hospitalization is prolonged through Day 15. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy-related endpoints will be to compare the dapansutrile and placebo arms by the following measures: * Complete resolution of fever symptoms (feeling feverish, chills, shivering and/or sweating) and shortness of breath * Proportion of subjects with complete resolution by study visits on Days 8, 15, 29, and 45 * Time to complete resolution; * WHO Ordinal Scale for Clinical Improvement * Clinical status at Day 8, Day 15, and Day 29 * Mean change from baseline at Day 8, Day 15, and Day 29; * Oxygenation * Oxygenation-free days from Day 1 through Day 15 * Incidence, timing and duration of new oxygen use through Day 45; * Mechanical ventilation * Mechanical ventilator-free days from Day 1 through Day 15 * Incidence, timing and duration of mechanical ventilation use through Day 45; * Hospitalization * Duration of hospital stay (days) due to COVID-19 (note: if the PI has chosen to treat the subject for COVID-19 on an in-patient basis, this is not applicable); * Mortality * Incidence of death through Day 45; * Fever * Number of days with fever (> 38*C / 100.4*F); * Diarrhea * Severity and frequency through Day 15; * Vomiting * Severity and frequency through Day 15; * Loss of taste and Loss of smell * Severity through Day 15; * All symptoms relevant to COVID-19 * Severity and frequency through Day 15; * Immunological and inflammatory labs, COVID-19 biomarkers, and cytokine biomarkers * Mean change from baseline through Day 15 in the following: ALT, AST, Creatinine, C3a, CRP, D-dimer, Ferritin, G-CSF, IL-1*, IL-6, IL-18, IP-10, LDH, Platelets, White blood cell (WBC) count. Safety variables collected in the study will be: * AEs during the clinical trial; * Safety laboratory measures (chemistry, hematology, and urinalysis); * Vital signs (pulse, respiratory rate, resting blood pressure, temperature, and oxygen saturation/SpO2). The safety endpoints in the study will evaluate the safety of dapansutrile relative to p | — |
Countries
Netherlands
Outcome results
None listed