Clinical trial: Intravenous Zotatifin in Adults With Mild or Moderate COVID-19 (NCT04632381)

Eligibility criteria:
Inclusion Criteria:

          1. Has provided informed consent and any authorizations required by local law;

          2. Is a male or female patient ≥18 and <65 years of age;

          3. Has a laboratory-documented positive test for SARS CoV 2 infection as determined by
             local laboratory using a standard, Food and Drug Administration (FDA)-approved viral
             RNA or viral antigen assay from any oral or respiratory sample collected within 48
             hours of randomization;

          4. Has at least 2 symptoms associated with COVID-19 (fever or chills, cough, shortness of
             breath or difficulty breathing on exertion, fatigue, muscle or body aches, headache,
             new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting,
             or diarrhea) starting no more than 5 days prior to randomization and has mild or
             moderate disease at screening and at time of randomization, defined as the following:

               -  Mild COVID-19

                    -  Positive testing by standard reverse transcriptase polymerase chain reaction
                       (RT-PCR) assay or equivalent test;

                    -  Symptoms of mild illness with COVID-19 that could include fever, cough, sore
                       throat, malaise, headache, muscle pain, gastrointestinal symptoms, without
                       shortness of breath or dyspnea; and

                    -  No clinical signs indicative of moderate, severe, or critical severity;

               -  Moderate COVID-19

                    -  Positive testing by standard RT-PCR assay or equivalent testing;

                    -  Symptoms of moderate illness with COVID-19, which could include any symptom
                       of mild illness or shortness of breath with exertion;

                    -  Clinical signs suggestive of moderate illness with COVID-19, such as
                       respiratory rate ≥20 breaths per minute, saturation of oxygen (SpO2) >93% on
                       room air at sea level, heart rate ≥90 beats per minute; and

                    -  No clinical signs indicative of severe or critical severity;

          5. Has adequate hepatic function during screening, defined as the following:

               -  Serum alanine aminotransferase ≤3 × upper limit of normal (ULN);

               -  Serum aspartate aminotransferase ≤3 × ULN; and

               -  Serum bilirubin (total) ≤1.5 × ULN (unless due to Gilbert's syndrome or
                  hemolysis);

          6. Has adequate bone marrow function during screening, defined as the following:

               -  Absolute neutrophil count ≥1.0 × 10 9/L;

               -  Platelet count ≥75 × 109/L; and

               -  Hemoglobin ≥90 g/L (9.0 g/dL or 5.6 mmol/L);

          7. Has adequate renal function during screening, defined as measured or estimated
             glomerular filtration rate ≥60 mL/min, calculated by the Cockcroft-Gault formula using
             actual body weight;

          8. Female patients of childbearing potential must meet all of the following criteria:

               -  Is not pregnant (confirmed via a negative urine pregnancy test);

               -  Is not breastfeeding; and

               -  Is willing to use a protocol-recommended method of contraception or willing to
                  abstain from heterosexual intercourse from the start of blinded study drug until
                  at least 90 days after the last dose of blinded study drug; Note: A female
                  patient is considered to be of childbearing potential unless she has had a
                  hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically
                  documented ovarian failure (with serum estradiol and follicle-stimulating hormone
                  levels within the institutional laboratory postmenopausal range and a negative
                  serum or urine β-human chorionic gonadotropin); or is menopausal (age ≥55 years
                  with amenorrhea for ≥6 months).

          9. Male patients who can father a child must meet all of the following criteria:

               -  Is willing to use a protocol-recommended method of contraception or willing to
                  abstain from heterosexual intercourse with females of childbearing potential from
                  the start of blinded study drug until at least 90 days after the last dose of
                  blinded study drug; and

               -  Is willing to refrain from sperm donation from the start of blinded study drug
                  until at least 90 days after the last dose of blinded study drug; Note: A male
                  patient is considered able to father a child unless he has had a bilateral
                  vasectomy with documented aspermia or a bilateral orchiectomy.

         10. Is willing to comply with the scheduled visits, drug administration plan,
             protocol-specified laboratory tests, other study procedures, and study restrictions;
             and Note: Psychological, social, familial, or geographical factors that may preclude
             adequate study participation should be considered.

         11. In the judgment of the Investigator, participation in the protocol offers an
             acceptable benefit to risk ratio when considering current disease status, medical
             condition, and the potential benefits and risks of alternative treatments for the
             patient's disease.

        Exclusion Criteria:

          1. Is hospitalized for COVID-19;

          2. Has dyspnea at rest or while talking, or has signs and symptoms of overt or impending
             respiratory failure;

          3. Has significant cardiovascular disease, defined by myocardial infarction, arterial
             thromboembolism, or cerebrovascular thromboembolism, within 3 months prior to
             randomization; symptomatic dysrhythmias or unstable dysrhythmias requiring medical
             therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York
             Heart Association Class 3 or 4 congestive heart failure; ≥Grade 3 hypertension
             (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg); or history
             of congenital prolonged QT syndrome;

          4. Has a history of chronic obstructive pulmonary disease or bronchial asthma requiring
             continuous treatment and/or intermittent or continuous oxygen within the 90 days prior
             to screening; Note: Intermittent use of a β2-agonist inhaler is allowed.

          5. Has evidence of an ongoing or systemic bacterial, fungal, or viral infection
             (including upper respiratory tract infections) other than SARS-CoV-2 infection,
             recurrent or repeat SARS CoV 2 infection, or history of incompletely treated
             tuberculosis (TB) and/or suspected or known extrapulmonary TB; Note: Patients with
             localized fungal infections of the skin or nails are eligible. Patients may be
             receiving topical antifungals. Systemic administration of azole antifungals is
             prohibited (see Section 5.6).

          6. Has significant infiltrates (involving >50% of lung parenchyma) on an optional
             standard of care chest X-ray or other lung imaging exam within 1 week of screening;

          7. Has known significant electrocardiogram abnormalities at screening, including unstable
             cardiac arrhythmia requiring medication, left bundle branch block, second-degree
             atrioventricular (AV) block type II, third-degree AV block, ≥Grade 2 bradycardia, or
             QTcF >450 msec for men or >470 msec for women;

          8. Has type 1 diabetes mellitus or type 2 diabetes mellitus;

          9. Has a body mass index (BMI) >30 kg/m2;

         10. Has received a live vaccine within 30 days prior to randomization;

         11. Has had major surgery within 4 weeks (inclusive) prior to randomization;

         12. Has had prior solid organ or bone marrow progenitor cell transplantation;

         13. Has a malignant tumor (excluding a malignant tumor cured with no recurrence in the
             past 2 years, completely resected basal cell and squamous cell carcinoma of the skin,
             and completely resected carcinoma in situ of any type);

         14. Has had prior high-dose chemotherapy requiring stem cell rescue;

         15. Has a history of or active uncontrolled systemic or local autoimmune disorders or
             other conditions that might impair or compromise the immune system;

         16. Has ongoing immunosuppressive therapy, including systemic corticosteroids; Note: At
             screening and during study participation, patients may be using systemic
             corticosteroids (doses ≤10 mg of prednisone or equivalent) or topical or inhaled
             corticosteroids.

         17. Has ongoing use of a therapeutic anticoagulant or history of bleeding disorder;

         18. Has ongoing use or plans to use antivirals against COVID-19;

         19. Has used a moderate or strong inhibitor or inducer of CYP3A4 within 7 days prior to
             randomization or is expected to require use of a moderate or strong CYP3A4 inhibitor
             or inducer during study participation;

         20. Has previously received investigational product in a clinical study within 30 days or
             within 5 elimination half-lives (whichever is shorter) prior to randomization or is
             planning to take part in another therapeutic clinical study while participating in
             this study; Note: Participation in observational studies is allowed.

         21. Has a known history of HIV or hepatitis B virus, or active hepatitis C virus
             infection;

         22. Has a known serious allergic reaction or hypersensitivity to components of zotatifin
             or placebo;

         23. Has a history of drug abuse or use of narcotics in the past 2 years that in the
             opinion of the Investigator will preclude study compliance; or

         24. Has any illness, medical condition, organ system dysfunction, or social situation,
             including mental illness or substance abuse, deemed by the Investigator to be likely
             to interfere with a patient's ability to provide informed consent, adversely affect
             the patient's ability to cooperate and participate in the study, or compromise the
             interpretation of study results.
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.
Subject must be at most 64 Years

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? Entailment