Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19)
Condition: Coronavirus
MeSH terms: COVID-19; Coronavirus Infections
Intervention: Silmitasertib
Intervention description: Standard of care / best supportive care in combination with CX-4945 1000 mg administered orally, two times a day.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SARS-CoV-2; COVID-19

Summary:

      This multi-center, open-label, 2 arm parallel-group, randomized, interventional prospective
      exploratory study in 40 patients aimed to evaluate safety and explore putative clinical
      benefits of Silmitasertib 1000 mg BID dose in patients with severe illness caused be
      SARS-COV-2. This will be a two-arm trial comparing the SOC/best supportive care alone to the
      SOC/best supportive care with addition of Silmitasertib (allocation ratio 1:1).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or non-pregnant female adult ≥ 18 years of age

          2. Diagnosed/confirmed with COVID-19 by standard RT-PCR assay or equivalent testing
             within 7 days prior to randomization (Day1).

          3. Hospitalized patient with severe illness caused by SARS-CoV-2 (Note: Prior or current
             use of remdesivir or dexamethasone (SOC) are allowed under the investigator's
             discretion. Concomitant treatment with other investigational antiviral drugs or
             immunomodulators are not permitted from Day1 through Day 28)

             Symptoms of severe systemic illness/infection with COVID-19:

             At least 1 of the following: fever, cough, sore throat, malaise, headache, muscle
             pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe
             lower respiratory infection including dyspnea at rest or respiratory distress AND
             Clinical signs indicative of severe systemic illness/infection with COVID-19 At least
             1 of the following: RR ≥ 30, HR ≥ 125, SaO2 <93% on room air or requires > 2L oxygen
             by nasal cannula in order to maintain SaO2 ≥93%

          4. Patient (or legally authorized representative) provides written informed consent prior
             to initiation of any study procedures.

          5. Adequate hematopoietic capacity, as defined by the following:

               1. Hemoglobin ≥ 9.0 g/dL and not transfusion dependent

               2. Platelets ≥ 100,000/mm3

               3. Absolute neutrophil count ≥ 1500 cells/mm3

          6. Adequate hepatic function, as defined by the following:

               1. AST and ALT ≤ 2.5 times upper limit of normal (ULN)

               2. Total bilirubin ≤ 1.5 x ULN

               3. Albumin ≥ 3.0 g/dL

          7. Adequate renal function, as defined by the following:

             a. Renal: calculated creatinine clearance >45 mL/min for patients with abnormal,
             increased creatinine levels (Cockcroft-Gault formula).

          8. Ability to take oral medication and be willing to adhere to drug administration and
             premedication requirements (see Section 6.3) throughout study duration.

        Exclusion Criteria:

          1. Patient showing signs of respiratory failure necessitating mechanical ventilation

          2. Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control; or
             abstinence) prior to study entry and for the duration of study participation. Should a
             man father a child, or a woman become pregnant or suspect she is pregnant while
             participating in this study, he or she should inform the treating physician
             immediately.

          3. Active or uncontrolled infections other than COVID-19 or with serious illnesses or
             medical conditions which would not permit the patient to receive study treatment

          4. Active or planned concomitant treatment with other investigational antivirals or
             immunomodulators

          5. Chronic diarrhea (excess of 2-3 stools/day above normal frequency)

          6. Current use or anticipated need for drugs that are known strong inhibitors or inducers
             of major CYP enzymes.