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).
This is a phase II multi-center, randomized, open-label, 2 arm parallel-group controlled
interventional prospective study of CX-4945 in patients with severe COVID-19. Up to
approximately 40 patients will be enrolled into this study. A screening evaluation will occur
within 7 days prior to Day 1. All qualified patients will be randomized at Day 1 in a ratio
of 1:1 to one of the following two treatment arms:
Arm A: SOC/ best supportive care in combination with CX-4945 1000 mg BID PO or Arm B: SOC/
best supportive care alone The standard of care (SOC) is not pre-specified, may vary among
patients, and may include agents with anti-viral activity, such as remdesivir, among others.
Investigator discretion is to be applied for any established SOC. Active concomitant
treatment with other investigational antivirals or immunomodulators are not permitted Best
supportive care is defined as intensive care therapy according to current guidelines,
evidence, and best practice, including but not limited to lung protective ventilation,
thrombosis prophylaxis, renal replacement therapy when indicated, and access to advanced
therapies including extracorporeal membrane oxygenation.
The total duration of the treatment will be 14 days. Patients will be followed up at 28, 45
and 60 days from the start of the treatment. The total duration for each patient in the study
(including the screening) will be up to 67 days.
Drug: Silmitasertib
Standard of care / best supportive care in combination with CX-4945 1000 mg administered orally, two times a day.
Other Name: CX-4945
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.
Banner University Medical Center Phoenix
Phoenix, Arizona, United States
Banner University Medical Center Tucson
Tucson, Arizona, United States