A Study of Silmitasertib (CX-4945) in Healthy Subject

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability of Silmitasertib

Conditions
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COVID-19

Intervention / Treatment
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* Drug: CX-4945


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects 20to 55 years of age, inclusive, at screening 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 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. Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, and electrocardiogram; Subject with acceptable hematology, biochemistry and urinalysis during screening period. Subject is willing and able to comply with study procedures and sign informed consent. Exclusion Criteria: 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. 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. Subject has received any prescription of drug within 3 days prior to study enrollment. Subject has drug abuse history. Any active or recurring clinically significant hepatic disease including HBV and HCV. Subject has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product. Any other medical reason as determined by the investigator.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CX-4945 200mg QD<br>CX-4945 will be administered at 200mg QD for continuously 5 days. | Drug: CX-4945<br>* Drug: CX-4945 Silmitasertib, orally, once or twice daily for 5 days. Other Name: Silmitasertib<br>* Other names: Silmitasertib;|
| Experimental: CX-4945 200mg BID<br>CX-4945 will be administered at 200mg BID for continuously 5 days. | Drug: CX-4945<br>* Drug: CX-4945 Silmitasertib, orally, once or twice daily for 5 days. Other Name: Silmitasertib<br>* Other names: Silmitasertib;|
| Experimental: CX-4945 400mg BID<br>CX-4945 will be administered at 400mg BID for continuously 5 days. | Drug: CX-4945<br>* Drug: CX-4945 Silmitasertib, orally, once or twice daily for 5 days. Other Name: Silmitasertib<br>* Other names: Silmitasertib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of CX-4945 administered orally 200mg QD, 200mg BID and 400mg BID for continuously 5 days in healthy subjects. | To evaluate the 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. | Day 1 to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate changes in blood chemistry. | Changes ALP in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in blood chemistry. | Changes AST in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in blood chemistry. | Changes ALT in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in blood chemistry. | Changes LDH in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in blood chemistry. | Changes CPK in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in blood chemistry. | Changes CRP in blood chemistry assessment from Day 1, Day 3, Day5, and Day 6 morning. | Day 1 to Day 6 | 
| To evaluate changes in other health assessment | Changes in ECG assessments from Day 1, Day 3, Day5, and Day 6 morning. A 12-lead ECG was performed at baseline (week 0), Day 3, Day5, and Day 6 and categorized as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). | Day 1 to Day 6 |