Clinical trial NCT04668209: Silmitasertib (CX-4945) in Patients With Severe Coronavirus Disease 2019 (COVID-19)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Coronavirus
Keywords: SARS-CoV-2
COVID-19
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Senhwa Biosciences, Inc.
First posted: 2020-12-16
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

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.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events [Safety and Tolerability]
timeFrame: Through Day 60
Secondary outcomes:
measure: To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.
timeFrame: Through Day 28
measure: To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.
timeFrame: Through hospital discharge, an average of 28 days
measure: To Compare Time to Clinical Recovery in CX-4945 Treatment Group Evaluated From Randomization Through Day 28 as Compared to the Control Arm.
timeFrame: Through Day 28
measure: To Compare Changes in Clinical Status of Patients Enrolled to CX-4945 Treatment Arm as Compared to the Control Arm at Day 14 and Day 28.
timeFrame: Assessed on Day 14 and Day 28
measure: To Compare Changes in Clinical Status of Patients Enrolled to CX-4945 Treatment Arm as Compared to the Control Arm at Day 14 and Day 28.
timeFrame: Through Day 28
measure: To Evaluate Preliminary Evidence of Anti-viral Activity of CX-4945 as Compared to the Control Arm.
timeFrame: Assessed at Day 1, Day 8, Day 14 and Day 28
measure: To Evaluate Preliminary Evidence of Anti-viral Activity of CX-4945 as Compared to the Control Arm.
timeFrame: Through Day 14
measure: Number of Days Hospitalized
timeFrame: Through Day 28
measure: To Evaluate Changes in IL-6 Level
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: To Evaluate Changes in CRP
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: To Evaluate Changes in LDH
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: To Evaluate Changes in CPK
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: To Evaluate Changes in Ferritin
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: To Evaluate Changes in D-dimer
timeFrame: Assessed on Days 1, 4, 8, 11, and 14
measure: Number of Days of Supplemental Oxygen Use
timeFrame: Through Day 28
measure: All-cause Mortality Status
timeFrame: Through Day 60
measure: Number of Days of On-invasive Ventilation/High Flow Oxygen
timeFrame: Through Day 28
measure: Number of Days of Invasive Mechanical Ventilation/ECMO
timeFrame: Through Day 28
measure: Number of Patients Returned to Room Air
timeFrame: Through Day 28
measure: Change in Pulse Oxygen Saturation
timeFrame: Days 4, 8, 11, 14, and 28
measure: Number of Thrombosis Events
timeFrame: Through Day 28
measure: Changes in EQ-D5-5L
timeFrame: Days randomization, 8, 14 and 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center Tucson
state: Arizona
Study officials:
References: