Clinical Trials List
Protocol NumberCX4945-AV06-phase II
NCT Number(ClinicalTrials.gov Identfier)NCT06202521
Completed
2023-05-01 - 2024-04-29
Phase II
Recruiting1
ICD-10J12.0
Adenoviral pneumonia
ICD-9480.0
Pneumonia due to adenovirus
A Phase Ⅱ,Double-blind,Randomized,Controlled Study to Evaluate the Safety and Efficacy of Silmitasertib(CX-4945) in Hospitalized Adults with COVID-19
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Trial Applicant
QPS
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Sponsor
-
Trial scale
Taiwan Single Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 李佳雯 Division of Infectious Disease
- 蔡進相 Division of Infectious Disease
- 羅景霳 Division of Infectious Disease
- 李明吉 Division of Infectious Disease
- 蔡文嘉 Division of Infectious Disease
- 陳嫈文 Division of Infectious Disease
- Wen-Chien Ko Division of Infectious Disease
- 薛伶珊 Division of Infectious Disease
- 冉浩恩 Division of Infectious Disease
- Po-Lin Chen Division of Infectious Disease
- 羅景霳 Division of Infectious Disease
- 游天瑜
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Community-acquired Pneumonia 、SARS-CoV-2 -Associated Pneumonia 、Influenza With Pneumonia
Objectives
main target
Evaluating the safety and tolerability of CX-4945 in adult hospitalized adults with severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2)-positive coronavirus disease 2019 (COVID-19)
secondary goals
Evaluating the efficacy of CX-4945 in adult hospitalized patients with SARS-CoV-2-positive COVID-19
Test Drug
CX-4945
Active Ingredient
Silmitasertib
Dosage Form
capsule
Dosage
200 mg/capsule
Endpoints
Main evaluation indicators
•Safety variables include (but are not limited to) vital assessment, physical examination, clinical laboratory test evaluation (hematology, biochemistry, coagulation, urinalysis, etc.), 12-lead electrocardiogram (ECG), chest X-ray (CXR), and adverse events (AE) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
•Proportion of subjects with treatment-emergent AEs (TEAEs) leading to discontinuation of study drug.
Secondary evaluation metrics
•Changes from the base period in the World Health Organization (WHO) ordinal table on days 2, 3, 4, 5, 7, 14, 30 and discharge day (if applicable).
•The time of clinical improvement in COVID-19 on days 2, 3, 4, 5, 7, 14, 30 and discharge day (if applicable). Clinical improvement was defined as a change of more than 2 points on the WHO ordinal scale from the positive base period.
The cycle number threshold (Ct) measured by the "SARS-CoV-2 reverse transcription"-polymerization chain reaction (RT-PCR) test on days 3, 5, 14, and 30 and the change in discharge date (if applicable) from the base period.
The time to clearance of SARS-CoV-2 is defined as the time from random assignment to the first two consecutive negative RT-PCR test results (sampling interval 24 hours).
•Proportion of subjects requiring admission to the intensive care unit within 30 days.
•The proportion of subjects who are alive and free of respiratory failure at day 30, as determined by the trial moderator.
•Number and proportion of subjects receiving baricitinib who discontinued trial treatment.
exploratory evaluation metrics
•Ferritin, C-reactive protein (CRP), D-dimer (D-dimer), lactate dehydrogenation (LDH), neutrophil to lymphocyte ratio (NLR), neutropenia Neutrophil to CD4+ T lymphocyte ratio (N4R), neutrophil to CD3+ T lymphocyte ratio (N3R), leukocyte growth factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) Changes from the base period on the 3rd, 5th, 7th, 14th and 30th days.
•Interleukin-1b (IL-1b), IL-2, IL-6, IL-7, IL-8, IL-10, IL-18, monocyte chemotaxis stimulating protein-1 (MCP -1), changes in fibrinolytic activation inhibitor type 1 (PAI-1) on days 3, 5, 7, 14, and 30 relative to the base period.
•The proportion of subjects diagnosed with COVID-19 who subsequently developed acute respiratory distress syndrome (ARDS), based on the 2012 Berlin definition of ARDS:
►Time point: Within 1 week of known clinical impairment or new or worsening respiratory syndrome.
►Chest angiography: Bilateral opacities on chest radiographs or computed tomography (CT) scans that cannot be fully explained by effusion, lobe/lung collapse, or nodules.
►Cause of edema: Respiratory failure that cannot be fully explained by heart failure or volume overload. If there are no risk factors, objective assessment of edema (e.g., cardiac ultrasound) should be performed to rule out hydrostatic pulmonary edema.
►The degree of hypoxemia may be:
°Mild (200 mmHg < PaO2/FiO2 ≤ 300 mmHg)
°Moderate (100 mmHg < PaO2/FiO2 ≤ 200 mmHg)
°Severe (PaO2/FiO2 ≤ 100 mmHg)
•All-cause mortality occurring within 30 days.
•Concomitant medications related to COVID-19 treatment used within 30 days, if any.
•Safety variables include (but are not limited to) vital assessment, physical examination, clinical laboratory test evaluation (hematology, biochemistry, coagulation, urinalysis, etc.), 12-lead electrocardiogram (ECG), chest X-ray (CXR), and adverse events (AE) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
•Proportion of subjects with treatment-emergent AEs (TEAEs) leading to discontinuation of study drug.
Secondary evaluation metrics
•Changes from the base period in the World Health Organization (WHO) ordinal table on days 2, 3, 4, 5, 7, 14, 30 and discharge day (if applicable).
•The time of clinical improvement in COVID-19 on days 2, 3, 4, 5, 7, 14, 30 and discharge day (if applicable). Clinical improvement was defined as a change of more than 2 points on the WHO ordinal scale from the positive base period.
The cycle number threshold (Ct) measured by the "SARS-CoV-2 reverse transcription"-polymerization chain reaction (RT-PCR) test on days 3, 5, 14, and 30 and the change in discharge date (if applicable) from the base period.
The time to clearance of SARS-CoV-2 is defined as the time from random assignment to the first two consecutive negative RT-PCR test results (sampling interval 24 hours).
•Proportion of subjects requiring admission to the intensive care unit within 30 days.
•The proportion of subjects who are alive and free of respiratory failure at day 30, as determined by the trial moderator.
•Number and proportion of subjects receiving baricitinib who discontinued trial treatment.
exploratory evaluation metrics
•Ferritin, C-reactive protein (CRP), D-dimer (D-dimer), lactate dehydrogenation (LDH), neutrophil to lymphocyte ratio (NLR), neutropenia Neutrophil to CD4+ T lymphocyte ratio (N4R), neutrophil to CD3+ T lymphocyte ratio (N3R), leukocyte growth factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) Changes from the base period on the 3rd, 5th, 7th, 14th and 30th days.
•Interleukin-1b (IL-1b), IL-2, IL-6, IL-7, IL-8, IL-10, IL-18, monocyte chemotaxis stimulating protein-1 (MCP -1), changes in fibrinolytic activation inhibitor type 1 (PAI-1) on days 3, 5, 7, 14, and 30 relative to the base period.
•The proportion of subjects diagnosed with COVID-19 who subsequently developed acute respiratory distress syndrome (ARDS), based on the 2012 Berlin definition of ARDS:
►Time point: Within 1 week of known clinical impairment or new or worsening respiratory syndrome.
►Chest angiography: Bilateral opacities on chest radiographs or computed tomography (CT) scans that cannot be fully explained by effusion, lobe/lung collapse, or nodules.
►Cause of edema: Respiratory failure that cannot be fully explained by heart failure or volume overload. If there are no risk factors, objective assessment of edema (e.g., cardiac ultrasound) should be performed to rule out hydrostatic pulmonary edema.
►The degree of hypoxemia may be:
°Mild (200 mmHg < PaO2/FiO2 ≤ 300 mmHg)
°Moderate (100 mmHg < PaO2/FiO2 ≤ 200 mmHg)
°Severe (PaO2/FiO2 ≤ 100 mmHg)
•All-cause mortality occurring within 30 days.
•Concomitant medications related to COVID-19 treatment used within 30 days, if any.
Inclution Criteria
Inclusion Criteria:
Not currently hospitalized.
Males or non-pregnant females aged ≥ 18 years at the time of signing the informed consent form (ICF)
Patients diagnosed with viral pneumonia, as determined by the investigator, who exhibit any of the subsequent criteria: presence of respiratory symptoms or fever.
With a pneumonia severity index (PSI) of risk class II or III
Oxygen saturation measured by pulse oximetry (SpO2) ≥94% on room air at sea level
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
Confirmed lower respiratory tract infection by X-ray.
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
The participant (or legal representative) agrees to adhere to study protocols and has signed the IRB-approved Informed Consent Form (ICF)
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.
Not currently hospitalized.
Males or non-pregnant females aged ≥ 18 years at the time of signing the informed consent form (ICF)
Patients diagnosed with viral pneumonia, as determined by the investigator, who exhibit any of the subsequent criteria: presence of respiratory symptoms or fever.
With a pneumonia severity index (PSI) of risk class II or III
Oxygen saturation measured by pulse oximetry (SpO2) ≥94% on room air at sea level
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
Confirmed lower respiratory tract infection by X-ray.
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
The participant (or legal representative) agrees to adhere to study protocols and has signed the IRB-approved Informed Consent Form (ICF)
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
Exclusion Criteria:
Subject received investigational treatment within 30 days prior to the study, or concurrent use of another investigational drug.
Subject has a history of severe renal disease (required phosphate binders or dialysis).
Subject has chronic diarrhea, characterized by three or more loose stools daily for a minimum of four weeks.
High likelihood of mortality within the next 48 hours, as assessed by the investigator.
Subject showing signs of respiratory failure and mechanical ventilation is required.
Subject with liver cirrhosis
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
Known active tuberculosis.
Current documented bacterial infection.
Subject has a documented anaphylactic reaction, regardless of cause.
Subject who has taken an antiviral agent against respiratory viral infection for a continuous duration of more than 24 hours before screening.
Subject is with active gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
Subjects received warfarin within 14 days prior to screening or intend to during the screening or treatment phase.
History of allergic reactions to any of the ingredients or components used in the manufacture of CX-4945.
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.
ALT or AST levels > 5 times upper limit of normal (ULN)
eGFR < 30 mL/min/1.73m2 (calculated by the MDRD formula)
Absolute neutrophil count (ANC) <1000/μL
Have received treatment with a SARS-CoV-2 specific monoclonal antibody
Have received convalescent COVID-19 plasma treatment
Concurrent use of baricitinib
Any physical findings or illness history that may compromise study results or increase patient risk, as determined by the investigator.
Subject received investigational treatment within 30 days prior to the study, or concurrent use of another investigational drug.
Subject has a history of severe renal disease (required phosphate binders or dialysis).
Subject has chronic diarrhea, characterized by three or more loose stools daily for a minimum of four weeks.
High likelihood of mortality within the next 48 hours, as assessed by the investigator.
Subject showing signs of respiratory failure and mechanical ventilation is required.
Subject with liver cirrhosis
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
Known active tuberculosis.
Current documented bacterial infection.
Subject has a documented anaphylactic reaction, regardless of cause.
Subject who has taken an antiviral agent against respiratory viral infection for a continuous duration of more than 24 hours before screening.
Subject is with active gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
Subjects received warfarin within 14 days prior to screening or intend to during the screening or treatment phase.
History of allergic reactions to any of the ingredients or components used in the manufacture of CX-4945.
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.
ALT or AST levels > 5 times upper limit of normal (ULN)
eGFR < 30 mL/min/1.73m2 (calculated by the MDRD formula)
Absolute neutrophil count (ANC) <1000/μL
Have received treatment with a SARS-CoV-2 specific monoclonal antibody
Have received convalescent COVID-19 plasma treatment
Concurrent use of baricitinib
Any physical findings or illness history that may compromise study results or increase patient risk, as determined by the investigator.
The Estimated Number of Participants
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Taiwan
48 participants
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Global
48 participants
