CX-4945 in Viral Community Acquired Pneumonia

Evaluation of the Safety and Efficacy of Silmitasertib (CX-4945) in Combination With Standard of Care (SOC) for Treating Patients With Community-Acquired Pneumonia (CAP) Associated With SARS-CoV-2 and Influenza Viral Infections

This is a Phase II, multi-center, double-blind, randomized, interventional study in approximately 120 subjects to evaluate clinical benefit of CX-4945 in adult outpatients with SARS-CoV-2 and influenza viral infection-associated pneumonia. The subjects will be recruited into two domains, including SARS-CoV-2 and influenza virus domains. The study will compare the efficacy of Standard of Care (SOC) combined with CX-4945 against SOC paired with a placebo, utilizing a 1:1 allocation ratio in each domain.

Study Overview

• Status: Terminated
• Conditions: Community-acquired Pneumonia; Influenza With Pneumonia; SARS-CoV-2 -Associated Pneumonia
• Intervention / Treatment: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Veterans General Hospital
  • New Taipei City, Taiwan
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • National Taiwan University Cancer Center, National Taiwan University Hospital
  • Taoyuan District, Taiwan
    • Taoyuan General Hospital, Ministry of Health and Welfare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SARS-CoV-2 domain: CX-4945 (400 mg BID for 5 days) +SOC; Notes: The SOC within the SARS-CoV-2 domain is defined as the medications in use at each respective site for the treatment of CAP related to SARS-CoV-2 infection.	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 Names: Silmitasertib
Placebo Comparator: SARS-CoV-2 domain: Placebo + SOC; Notes: The SOC within the SARS-CoV-2 domain is defined as the medications in use at each respective site for the treatment of CAP related to SARS-CoV-2 infection.	Drug: Placebo (SARS-CoV-2 domain); The dosage and frequency is the same as active drug.
Experimental: Influenza virus domain: CX-4945 (400 mg BID for 5 days) +SOC; Notes: The SOC within the influenza virus domain is defined as the medications in use at each respective site for the treatment of CAP related to influenza virus infection.	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 Names: Silmitasertib
Placebo Comparator: Influenza virus domain: Placebo + SOC; Notes: The SOC within the influenza virus domain is defined as the medications in use at each respective site for the treatment of CAP related to influenza virus infection.	Drug: Placebo (Influenza virus domain); The dosage and frequency is the same as active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects Requiring Hospitalization, Including Emergency Room Visits, or Resulting in Death Due to Progression of CAP Related to SARS-CoV-2 or Influenza.	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared to placebo plus SOC, in preventing the progression of CAP associated with SARS-CoV-2 and influenza virus infection	Day 1 to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects With All Cause Hospitalization, Emergency Room Visits, or Death During Study Period.	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition	Day 1 to Day 29
The Percentage of Subjects With Improved Pulmonary X-ray Findings for Pneumonia, Relative to Baseline or Showing a Return to Normalcy	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition. Note: Visit 3 and its associated efficacy/safety assessments were scheduled for Day 5 in protocol version 1.0 and for Day 7 since protocol version 2.0.	Baseline to Day 5/7
The Symptom Resolution for Fever is Defined as Body Temperature Lower Than the Following Definition for 24 Hours (Ear Temperature < 38 °C, Base of the Tongue Temperature < 37.5 °C, or Axillary Temperature < 37 °C)	Time to Symptom Resolution for Fever [days]. The symptom resolution for fever is defined as body temperature lower than the following definition (ear temperature < 38 °C, base of the tongue temperature < 37.5 °C, or axillary temperature < 37 °C) Note: Visit 3 and its associated efficacy/safety assessments were scheduled for Day 5 in protocol version 1.0 and for Day 7 since protocol version 2.0.	Day 1 to Day 5/7
Change From Baseline in SpO2/FiO2 Ratio	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition Note: Visit 3 and its associated efficacy/safety assessments were scheduled for Day 5 in protocol version 1.0 and for Day 7 since protocol version 2.0.	Day 1 to Day 5/7, 15, and 29
The Percentage of Subjects Exhibiting Disease Progression in Health Status Disease Progression is Defined as an Increase of Score on the National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition. NIAID 8-point ordinal scale range: 1-8, with higher scores indicating a worse condition. Note: Visit 3 and its associated efficacy/safety assessments were scheduled for Day 5 in protocol version 1.0 and for Day 7 since protocol version 2.0.	Day 1 to Day 5/7, 15, and 29
The Percentage of Subjects Exhibiting Health Improvement in Health Status Health Improvement is Defined as a Reduction of Score on the National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition NIAID 8-point ordinal scale range: 1-8, with higher scores indicating a worse condition. Note: Visit 3 and its associated efficacy/safety assessments were scheduled for Day 5 in protocol version 1.0 and for Day 7 since protocol version 2.0.	Day 1 to Day 5/7, 15, and 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of subjects achieving normalized C-reactive protein (CRP) levels on Day 7. This assessment will only be conducted in subjects whose CRP levels exceed the upper limit of normal (ULN) at Visit 2.	To evaluate the effect of intervention with Silmitasertib (CX 4945) in addition to SOC, compared with placebo plus SOC, on inflammatory status	Day 7
Change from baseline in ferritin, CRP, CAR, D-dimer, LDH, NLR, and PLR	To evaluate the effect of intervention with Silmitasertib (CX 4945) in addition to SOC, compared with placebo plus SOC, on inflammatory status	Day 1 to Day 7, 15 , and 29
Changes from baseline in serum cytokine levels: Cytokines to be quantified; IL-6, IL-1β, TNF-α, CCL2, IL-8 and IFN-γ	To evaluate the effect of intervention with Silmitasertib (CX 4945) in addition to SOC, compared with placebo plus SOC, on moderating the elevated cytokine release associated with SARS CoV 2 and Influenza virus infection	Day 1 to Day 7, 15 , and 29

Collaborators and Investigators

• Sponsor: Senhwa Biosciences, Inc.
• Investigators: Study Chair: Jason Huang, M.D., Senhwa Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Actual): April 22, 2025
• Study Completion (Actual): April 22, 2025

Study Registration Dates

• First Submitted: January 1, 2024
• First Submitted That Met QC Criteria: January 1, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Covid-19; Community-acquired Pneumonia
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Community-Acquired Infections; COVID-19; Influenza, Human; Community-Acquired Pneumonia; silmitasertib
• Other Study ID Numbers: CX-4945-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes