COVID-19
Conditions
Brief summary
This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.
Detailed description
COVID-19 is characterized by SARS-CoV-2 induced up-regulation of host protein kinase CK2 that catalyzes phosphorylation of many proteins, modulating their activities in cellular processes. CX-4945 demonstrated anti-viral efficacy in COVID-19 in vitro studies. In CX4945-AV01-IIT(IND 152726), CX-4945 was a safe treatment at 1000 mg BID regimen supported by the fact of no occurrence of treatment related Grade ≥ 3 AE, death or SUSAR. There were approximately 50 % of patients who experienced gastrointestinal disorders of grade 1-2. In CX4945-AV01-IIT, an out-patient study, there were 50% experienced gastrointestinal disorders. To further evaluate the safety and tolerability of CX-4945, this phase 1 study will use lower doses and subjects will be close-monitored to evaluate the safety.
Interventions
DRUGCX-4945
Drug: CX-4945 Silmitasertib, orally, once or twice daily for 5 days. Other Name: Silmitasertib
Sponsors
Senhwa Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects 20to 55 years of age, inclusive, at screening 2. Body mass index (BMI)within the range of 18.0 to 30.0 kg/m2, inclusive, and a minimum weight of 50.0 kg at screening 3. Subjects who are of reproductive potential agreed to remain abstinent or use (or have their partner use) an acceptable method of birth control (intrauterine device, hormonal contraception, vasectomy or condom) from screening until at least 2 weeks after the last study drug administration. 4. Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, and electrocardiogram; 5. Subject with acceptable hematology, biochemistry and urinalysis during screening period. 6. Subject is willing and able to comply with study procedures and sign informed consent.
Exclusion criteria
1. 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 from screening until at least 2 weeks after the last study drug administration. 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. 2. Active or uncontrolled infections such asCOVID-19, HIV or with serious illnesses or medical conditions which would not permit the subject to receive study treatment. 3. Subject has received any prescription of drug within 3 days prior to study enrollment. 4. Subject has drug abuse history. 5. Any active or recurring clinically significant hepatic disease including HBV and HCV. 6. Subject has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product. 7. Any other medical reason as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAT) | Day 1 to Day 5 | Evaluate the number adverse events occurring from Day 1 to Day 5 as characterized by type, frequency, severity \[as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0\], timing, seriousness, and relationship to study therapy after administration of 200mg QD, 200mg BID and 400mg BID for continuously 5 days to healthy subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Changes in Blood Chemistry. | Day 1 to Day 6 | Changes ALP in blood chemistry assessment from Day 1(Baseline) to Day 6 morning. |
| To Evaluate Changes in Blood Chemistry. | Day 1 to Day 6 | Changes ALT in blood chemistry assessment from Day 1(Baseline) to Day 6 morning. |
| Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Screening, Day 1, Day 3, Day 5, and Day 6 | ECG assessments were done during Screening, Day 1, Day 3, Day 5, and Day 6. A 12-lead ECG was performed at baseline (Day1), Day 3, Day 5, and Day 6 and categorized as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). |
Countries
Taiwan
Participant flow
Recruitment details
Participants were recruited from healthy subjects at Taipei Medical University Hospital between November 2022 and December 2022. The first participant was enrolled on November 28th, 2022, and the last was enrolled in 28th December 2022.
Pre-assignment details
30 enrolled participants met inclusion criteria and were randomized.
Participants by arm
| Arm | Count |
|---|---|
| CX-4945 200mg QD CX-4945 was administered at 200mg QD for continuously 5 days. | 10 |
| CX-4945 200mg BID CX-4945 was administered at 200mg BID for continuously 5 days. | 10 |
| CX-4945 400mg BID CX-4945 was administered at 400mg BID for continuously 5 days. | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | CX-4945 200mg QD | Total | CX-4945 400mg BID | CX-4945 200mg BID |
|---|---|---|---|---|
| Age, Continuous | 33.5 years | 33.5 years | 37.5 years | 32 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 30 Participants | 10 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Taiwan | 10 participants | 10 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 20 Participants | 8 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 10 | 3 / 10 | 7 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAT)
Evaluate the number adverse events occurring from Day 1 to Day 5 as characterized by type, frequency, severity \[as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0\], timing, seriousness, and relationship to study therapy after administration of 200mg QD, 200mg BID and 400mg BID for continuously 5 days to healthy subjects.
Time frame: Day 1 to Day 5
Population: Treatment-Emergent Adverse Events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CX-4945 200mg QD | Number of Participants With Treatment-emergent Adverse Events (TEAT) | 1 Participants |
| CX-4945 200mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAT) | 3 Participants |
| CX-4945 400mg BID | Number of Participants With Treatment-emergent Adverse Events (TEAT) | 7 Participants |
Secondary
Evaluate Changes in Blood Chemistry.
Changes ALP in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | Evaluate Changes in Blood Chemistry. | -2.1 U/L | Standard Deviation 5.78 |
| CX-4945 200mg BID | Evaluate Changes in Blood Chemistry. | -0.3 U/L | Standard Deviation 6.62 |
| CX-4945 400mg BID | Evaluate Changes in Blood Chemistry. | 3.4 U/L | Standard Deviation 2.84 |
Secondary
Evaluate Changes in Blood Chemistry.
Changes AST in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | Evaluate Changes in Blood Chemistry. | -3.9 U/L | Standard Deviation 5.11 |
| CX-4945 200mg BID | Evaluate Changes in Blood Chemistry. | -2.4 U/L | Standard Deviation 3.72 |
| CX-4945 400mg BID | Evaluate Changes in Blood Chemistry. | 0.1 U/L | Standard Deviation 3.35 |
Secondary
Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG
ECG assessments were done during Screening, Day 1, Day 3, Day 5, and Day 6. A 12-lead ECG was performed at baseline (Day1), Day 3, Day 5, and Day 6 and categorized as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS).
Time frame: Screening, Day 1, Day 3, Day 5, and Day 6
Population: \[Not Specified\]
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CX-4945 200mg QD | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 5 | 5 Participants |
| CX-4945 200mg QD | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 3 | 7 Participants |
| CX-4945 200mg QD | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Screening | 7 Participants |
| CX-4945 200mg QD | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 1 (Baseline) | 3 Participants |
| CX-4945 200mg QD | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 6 | 6 Participants |
| CX-4945 200mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 3 | 9 Participants |
| CX-4945 200mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Screening | 6 Participants |
| CX-4945 200mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 1 (Baseline) | 4 Participants |
| CX-4945 200mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 5 | 6 Participants |
| CX-4945 200mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 6 | 6 Participants |
| CX-4945 400mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 6 | 6 Participants |
| CX-4945 400mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 5 | 7 Participants |
| CX-4945 400mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Screening | 6 Participants |
| CX-4945 400mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 3 | 6 Participants |
| CX-4945 400mg BID | Number of Participants Evaluated as Having Abnormalities (CS or NCS) in Their ECG | Day 1 (Baseline) | 8 Participants |
Secondary
To Evaluate Changes in Blood Chemistry.
Changes LDH in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | To Evaluate Changes in Blood Chemistry. | -17.0 U/L | Standard Deviation 17.17 |
| CX-4945 200mg BID | To Evaluate Changes in Blood Chemistry. | -26.2 U/L | Standard Deviation 10.75 |
| CX-4945 400mg BID | To Evaluate Changes in Blood Chemistry. | -28.2 U/L | Standard Deviation 14.33 |
Secondary
To Evaluate Changes in Blood Chemistry.
Changes CPK in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | To Evaluate Changes in Blood Chemistry. | -24.3 U/L | Standard Deviation 19.35 |
| CX-4945 200mg BID | To Evaluate Changes in Blood Chemistry. | -54.0 U/L | Standard Deviation 63.71 |
| CX-4945 400mg BID | To Evaluate Changes in Blood Chemistry. | -65.1 U/L | Standard Deviation 71.37 |
Secondary
To Evaluate Changes in Blood Chemistry.
Changes CRP in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | To Evaluate Changes in Blood Chemistry. | 0.003 mg/dL | Standard Deviation 0.1341 |
| CX-4945 200mg BID | To Evaluate Changes in Blood Chemistry. | -0.071 mg/dL | Standard Deviation 0.2497 |
| CX-4945 400mg BID | To Evaluate Changes in Blood Chemistry. | 0.002 mg/dL | Standard Deviation 0.0447 |
Secondary
To Evaluate Changes in Blood Chemistry.
Changes ALT in blood chemistry assessment from Day 1(Baseline) to Day 6 morning.
Time frame: Day 1 to Day 6
Population: Day 6 (EOT) - Change from Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CX-4945 200mg QD | To Evaluate Changes in Blood Chemistry. | -4.0 U/L | Standard Deviation 6.15 |
| CX-4945 200mg BID | To Evaluate Changes in Blood Chemistry. | -1.4 U/L | Standard Deviation 5.19 |
| CX-4945 400mg BID | To Evaluate Changes in Blood Chemistry. | 0.9 U/L | Standard Deviation 4.77 |