Phase II, Randomized, Investigator Initiated Trial to Evaluate Safety and to Explore Clinical Benefit of Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19)

CX4945-AV02-IIT

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).

2021-01-21

2022-06-30

2022-10-19

Terminated

Early phase I

31

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 31, 'type': 'ACTUAL'}}

2023-11-07