Clinical trial NCT06202521: CX-4945 in Viral Community Acquired Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Community-acquired Pneumonia
SARS-CoV-2 -Associated Pneumonia
Influenza With Pneumonia
Keywords: Covid-19
Influenza
Community-acquired Pneumonia
Lead sponsor: Senhwa Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Day 1 to Day 29
Secondary outcomes:
measure: The percentage of subjects with all cause hospitalization, emergency room visits, or death during study period.
timeFrame: Day 1 to Day 29
measure: The percentage of subjects with improved pulmonary X-ray findings for pneumonia, relative to baseline or showing a return to normalcy
timeFrame: Baseline to Day 7, 15, and 29
measure: 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)
timeFrame: Day 1 to Day 7
measure: Change from baseline in SpO2/FiO2 ratio
timeFrame: Day 1 to Day 7, 15, and 29
measure: 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
timeFrame: Day 1 to Day 7, 15, and 29
measure: 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
timeFrame: Day 1 to Day 7, 15, and 29
measure: The percentage of subjects with a negative RT-PCR result for the SARS-CoV-2 (only for SARS-CoV-2 domain) or the influenza virus (only for influenza virus domain) on Day 7.
timeFrame: Day 1 and Day 7
measure: Change from baseline in viral load in nasal secretions by RT-PCR (only for SARS-CoV-2 domain)
timeFrame: Day 1 and Day 7
measure: Change from baseline in Ct values (only for SARS-CoV-2 domain)
timeFrame: Day 1 and Day 7
measure: TEAEs and SAEs
timeFrame: Day 1 to Day 29
measure: Laboratory test
timeFrame: Day 1 to Day 29
measure: Vital signs
timeFrame: Day 1 to Day 29
measure: Electrocardiogram (ECG) results
timeFrame: Baseline to Day 29
Other outcomes:
measure: 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.
timeFrame: Day 7
measure: Change from baseline in ferritin, CRP, CAR, D-dimer, LDH, NLR, and PLR
timeFrame: Day 1 to Day 7, 15 , and 29
measure: Changes from baseline in serum cytokine levels: Cytokines to be quantified; IL-6, IL-1β, TNF-α, CCL2, IL-8 and IFN-γ
timeFrame: Day 1 to Day 7, 15 , and 29
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center, National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: Taoyuan General Hospital, Ministry of Health and Welfare
Study officials:
affiliation: Senhwa Biosciences
name: Jason Huang, M.D.
role: STUDY_CHAIR
References: