A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of Orally Administered Dapansutrile Capsules for the Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome
- Conditions
- COVID-19Cytokine Release Syndrome10047438
- Registration Number
- NL-OMON50847
- Lead Sponsor
- Olatec Therapeutics LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
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.
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy-related endpoint will be to compare the dapansutrile and<br /><br>placebo arms by the following measure:<br /><br>Clinical deterioration, or lack of improvement, by Day 15, defined as either<br /><br>having any COVID-19-related hospitalization after enrollment OR meeting both<br /><br>criteria of (1) worsening or persistence of shortness of breath AND (2) oxygen<br /><br>saturation less than 92% on room air at sea level or need for supplemental<br /><br>oxygen to achieve oxygen saturation of 92% or greater . Note: If the PI has<br /><br>chosen to treat the subject for COVID-19 on an in-patient basis (e.g., the<br /><br>subject is elderly or frail), hospitalization is not considered clinical<br /><br>deterioration unless the other criteria have been met or hospitalization is<br /><br>prolonged through Day 15.</p><br>
- Secondary Outcome Measures
Name Time Method