This is a Phase II, multi-center, double-blind, randomized, interventional study inapproximately 120 subjects to evaluate clinical benefit of CX-4945 in adult outpatientswith SARS-CoV-2 and influenza viral infection-associated pneumonia. The subjects will berecruited into two domains, including SARS-CoV-2 and influenza virus domains. The studywill compare the efficacy of Standard of Care (SOC) combined with CX-4945 against SOCpaired with a placebo, utilizing a 1:1 allocation ratio in each domain.
Domain I: SARS-CoV-2 domain
- Arm 1: CX-4945 (400 mg BID for 5 days) +SOC
- Arm 2: Placebo + SOC
Domain II: Influenza virus domain
- Arm 3: CX-4945 (400 mg BID for 5 days) +SOC
- Arm 4: Placebo + SOC
Screening visit will collect health information and perform protocol specified tests to
determine patients' eligibility. After screening visit, eligible subjects who fulfill all
selection criteria for enrollment will be randomized into each of the arms. The CX-4945
will be administered at 400 mg BID for 5 days. Subjects will be followed up until Day 29.
Drug: CX-4945 (SARS-CoV-2 domain)
CX-4945 will be administered at 400 mg BID for up to 5 days (Day 1 to Day 5) in addition
to SOC.
Other Name: Silmitasertib
Drug: Placebo (SARS-CoV-2 domain)
The dosage and frequency is the same as active drug.
Drug: CX-4945 (Influenza virus domain)
CX-4945 will be administered at 400 mg BID for up to 5 days (Day 1 to Day 5) in addition
to SOC.
Other Name: Silmitasertib
Drug: Placebo (Influenza virus domain)
The dosage and frequency is the same as active drug.
Inclusion Criteria
1. Not currently hospitalized
2. Males or females aged ≥ 18 years at the time of signing the informed consent form
(ICF)
3. Patients diagnosed with viral pneumonia, as determined by the investigator, who
exhibit any of the subsequent criteria: presence of respiratory symptoms or fever
(ear temperature ≥ 38 °C, base of the tongue temperature ≥ 37.5 °C, or axillary
temperature ≥ 37 °C)
4. With a pneumonia severity index (PSI) of risk class II or III
5. Oxygen saturation measured by pulse oximetry (SpO2) ≥ 94% on room air at sea level
6. Positive test for SARS-CoV-2 or influenza virus infection, confirmed by rapid
diagnostic test (excluding cases where both SARS-CoV-2 and influenza virus are
positive)
7. Confirmed lower respiratory tract infection by X-ray
8. At screening, subjects capable of childbearing must provide a negative serum or
urine pregnancy test. These subjects must also commit to adhering to the
study-specified contraceptive methods throughout the study duration
Notes: Acceptable contraceptive methods include:
- Established use of oral, injected or implanted hormonal methods of
contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps)
9. The participant (or legal representative) agrees and is able to adhere to study
protocol-stated requirements, instructions, and restrictions in the investigator's
judgement. Furthermore, the participant is capable of understanding and has signed
the IRB-approved Informed Consent Form (ICF)
10. With at least two of the risk factors listed below: Age ≥ 50 years-old; cancer and a
life expectancy of ≥ 6 months; HIV infection; immunocompromised patient; congestive
heart failure (CHF), or coronary artery disease (CAD), or cardiomyopathies; chronic
kidney disease (CKD); chronic liver disease; chronic lung disease; diabetes mellitus
(DM); body mass index (BMI) > 25 kg/m2; asthma; cerebrovascular disease; cystic
fibrosis; dementia; or current and former smoker
Exclusion Criteria
1. Subject received investigational treatment within 30 days prior to the study, or
concurrent use of another investigational drug
2. Subject has a history of severe renal disease (required phosphate binders or
dialysis)
3. Subject has chronic diarrhea, characterized by three or more loose stools daily for
a minimum of four weeks
4. High likelihood of mortality within the next 48 hours, as assessed by the
investigator
5. Subject showing signs of respiratory failure and mechanical ventilation is required
6. Subject with liver cirrhosis
7. Subject with hepatitis B and/or hepatitis C disease, unless the subject has an
aspartate aminotransferase (AST) level ranging from 8 to 31 U/L and an alanine
aminotransferase (ALT) level from 0 to 41 U/L
8. Known active tuberculosis
9. Current documented bacterial infection
10. Subject has a documented anaphylactic reaction, regardless of cause
11. Subject who has taken an antiviral agent against respiratory viral infection for a
continuous duration of more than 24 hours before screening
12. Subject is with active gastrointestinal diseases including gastritis, ulcerative
colitis, Crohn's disease, or hemorrhagic coloproctitis
13. Subjects received warfarin within 14 days prior to screening or intend to during the
screening or treatment phase
14. History of allergic reactions to any of the ingredients or components used in the
manufacture of CX-4945
15. Women who are pregnant or breastfeeding, or planning pregnancy during the study
Note: Men and women of reproductive potential must commit to effective contraception
methods or abstinence during the study. Any resulting pregnancies or suspected
pregnancies must be reported to the treating physician immediately.
16. ALT or AST levels > 5 times upper limit of normal (ULN)
17. eGFR <30 mL/min/1.73m2 (calculated by the MDRD formula)
18. Absolute neutrophil count (ANC) <1000/μL
19. Have received treatment with a SARS-CoV-2 specific monoclonal antibody
20. Have received convalescent COVID-19 plasma treatment
21. Concurrent use of baricitinib
22. Any physical findings or illness history that may compromise study results or
increase patient risk, as determined by the investigator
Kaohsiung Veterans General Hospital
Kaohsiung, Taiwan
Far Eastern Memorial Hospital
New Taipei City, Taiwan
Taichung Veterans General Hospital
Taichung, Taiwan
National Taiwan University Cancer Center, National Taiwan University Hospital
Taipei, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Tri-Service General Hospital
Taipei, Taiwan
Taoyuan General Hospital, Ministry of Health and Welfare
Taoyuan, Taiwan
Becky Lin
+886-2-8911-9856
beckylin@senhwabio.com
Hylee Lee
+886-2-8911-9856
Hylee@senhwabio.com
Jason Huang, M.D., Study Chair
Senhwa Biosciences