Phase II, Double Blind, Randomized Trial of 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: Not yet recruiting
• 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

After screening visit, eligible subjects who fulfill all selection criteria for enrollment will be randomized into each of the arms. CX-4945 will be administered at 400 mg BID for up to 5 days. After treatment phase, subjects will be followed up for 28 days.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Becky Lin; Phone Number: +886-2-8911-9856; Email: beckylin@senhwabio.com
• Study Contact Backup: Name: Hylee Lee; Phone Number: +886-2-8911-9856; Email: Hylee@senhwabio.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital

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 non-pregnant 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.
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 by FilmArray; if FilmArray is not available, a positive test can also be confirmed by a rapid diagnostic test or molecular diagnostic assay, using a nasopharyngeal specimen
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
9. The participant (or legal representative) agrees to adhere to study protocols 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 Notes: 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, 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 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	Day 1 to Day 5, 15, and 29
Time to symptom resolution for fever. The symptom resolution for fever will be defined as body temperature of < 38°C.	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 5
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	Day 1 to Day 5, 15, and 29
The percentage of subjects exhibiting disease progression in health status	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 5, 15, and 29
The percentage of subjects exhibiting disease improvement in health status	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 5, 15, and 29
Change from baseline in viral load in nasal secretions by qRT-PCR. (only for SARS-CoV-2 domain)	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in reducing viral load	Day 1 and Day 5
Time to FilmArray confirmed resolution of viral infection	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in reducing viral load	Day 1 and Day 5
Change from baseline in Ct values (only for SARS-CoV-2 domain)	To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in reducing viral load	Day 1 and Day 5
TEAEs and SAEs	To evaluate the safety and tolerability of Silmitasertib (CX-4945)	Day 1 to Day 29
Laboratory test	To evaluate the safety and tolerability of Silmitasertib (CX-4945)	Day 1 to Day 29
Vital signs	To evaluate the safety and tolerability of Silmitasertib (CX-4945)	Day 1 to Day 29
Electrocardiogram results	To evaluate the safety and tolerability of Silmitasertib (CX-4945)	Day 1 to Day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of subject s achieving normalized CRP levels.	To evaluate the effect of intervention with Silmitasertib (CX 4945) in addition to SOC, compared with placebo plus SOC, on inflammatory status	Day 5
Change from baseline in ferritin, CRP, CAR, D-dimer, LDH, NLR, N4R, N3R, 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 5, 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 5, 15 , and 29

Collaborators and Investigators

• Sponsor: Senhwa Biosciences, Inc.
• Investigators: Study Chair: Jin-Ding Huang, PhD, Senhwa Biosciences

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 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 11, 2024
• Last Update Submitted That Met QC Criteria: January 1, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Influenza; Covid-19; Community-acquired Pneumonia
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Orthomyxoviridae Infections; Pneumonia; Influenza, Human
• 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