Clinical trial: Safety and Efficacy of Dapansutrile for Treatment of Moderate COVID-19 Symptoms and Evidence of Early Cytokine Release Syndrome (NCT04540120)

Eligibility 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 who have fever (temperature ≥ 38 ̊C / 100.4 ̊F) and
             shortness of breath (with exertion), not requiring oxygen, and meeting the definition
             of "moderate" as set forth by the May 2020 FDA Guidance for Industry: COVID-19:
             Developing Drugs and Biological Products for Treatment or Prevention (FDA, 2020),
             which includes all of the following criteria when the subject is sitting:

               1. Respiratory rate: ≥ 20 breaths/minute,

               2. SpO2: > 93% and ≤ 96% on room air at sea level, and

               3. Heart rate: ≥ 90 beats/minute;

          5. Subject must possess at least one of the following high-risk conditions known to have
             an underlying increased level of cytokine production:

               1. 70 years or more of age,

               2. Obesity (BMI ≥ 30 kg/m2),

               3. Diabetes (type 1 or 2),

               4. 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,

               5. Known respiratory disease (including asthma or chronic obstructive pulmonary
                  disease [COPD]),

               6. Known heart failure (note: subjects with New York Heart Association Class IV
                  congestive heart failure cannot be enrolled per Exclusion Criterion 4), or

               7. Known coronary disease;

          6. Plasma CRP level ≤ 20 mg/L within 72 hours of Screening/Baseline/Day 1 Visit;

          7. Acceptable overall medical condition to be safely enrolled in and complete the study
             (with specific regard to cardiovascular, renal, and hepatic conditions) 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:

          1. Women of childbearing potential, or men whose sexual partner(s) is a woman of
             childbearing potential, who:

               1. Are or intend to become pregnant (including use of fertility drugs) during the
                  study;

               2. Are nursing (female subjects only);

               3. 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;

          3. Evidence of moderate concurrent nervous system, renal, endocrine, or gastrointestinal
             disease, unrelated to COVID-19 as determined by the Investigator;

          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;

          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:

               1. 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

               2. 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 over the defined or planned
             use of any concomitant medications/therapies during the

             Treatment Period, including specifically:

               1. use of ibuprofen or diclofenac

               2. use of colchicine

               3. use of systemic steroids within 30 days of randomization

               4. use of janus kinase (JAK) inhibitors

               5. 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);

             Note: During the treatment period a patient may meet the criteria for a treatment
             approved by the FDA specifically for COVID-19 (e.g. remdesivir). In this situation the
             investigator and medical monitor should confer and take the most appropriate decision
             for the patient. If possible, the preference would be for the patient to complete the
             14 days of dosing before adding on the 2nd treatment. If that is not possible the
             preference would be for the patient to continue their 14 days on dapansutrile and
             complete all study related visits.

         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
             the cervix uteri that has been excised and cured);

         14. History of infection or known active infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);

         15. Any other concomitant medical or psychiatric conditions, diseases, or prior surgeries
             that, in the opinion of the Investigator, would impair the subject from safely
             participating in the trial and/or completing protocol requirements;

         16. Individuals who have been in a chronic care facility in the past 30 days;

         17. Individuals who are incarcerated;

         18. Participation in any clinical trial and/or use of any investigational product within
             the immediate 30-day period prior to the Screening/Baseline//Day 1 Visit; or receipt
             prior to Screening/Baseline/Day 1 Visit or intending to receive during the trial a
             COVID-19 vaccination.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): The patient is a 38-year-old man with cough and body ache that started 3 days ago.  He had fever and chills at the beginning and has low grade fever at the time of visit. He feels tired and sleepy. His body ache and myalgia get better after using Tylenol. The PCR test for Covid is positive. His vital signs are within normal limits with a body temperature of 37.9 C. There is no lymphadenopathy or white exudates in the pharynx.

Patient description (patient's own words): I was feeling really sick the other day, to the point that I showed up at the doctor's office. I was coughing, and my body was hurting for 3 days. I had a fever and chills and felt tired and sleepy. I got better after using Tylenol. They did a PCR Covid test on me, and it was positive! My vitals were normal, and my temperature was 37.9 C. I had no swelling around my neck or white spots on the back of my throat.

Does the patient match the trial criteria? Contradiction