Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia

Senhwa Biosciences

Status and phase: Not yet enrolling; Phase 2

Conditions: Influenza With Pneumonia; SARS-CoV-2 -Associated Pneumonia; Community-acquired Pneumonia

Treatments: Drug: CX-4945 (Influenza virus domain); Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: Placebo (Influenza virus domain)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06202521

CX-4945-011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 136 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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136 participants in 4 patient groups, including a placebo group

SARS-CoV-2 domain: CX-4945 (400 mg BID for 5 days) +SOC

Experimental group

Description:

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.

Treatment:

Drug: CX-4945 (SARS-CoV-2 domain)

SARS-CoV-2 domain: Placebo + SOC

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (SARS-CoV-2 domain)

Influenza virus domain: CX-4945 (400 mg BID for 5 days) +SOC

Experimental group

Description:

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.

Treatment:

Drug: CX-4945 (Influenza virus domain)

Influenza virus domain: Placebo + SOC

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo (Influenza virus domain)