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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 7
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Not currently hospitalized
- •Males or 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 (ear temperature ≥ 38 °C, base of the tongue temperature ≥ 37.5 °C, or axillary temperature ≥ 37 °C)
- •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, confirmed by rapid diagnostic test (excluding cases where both SARS-CoV-2 and influenza virus are positive)
- •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
- •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)
- •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)
- •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
排除标准
- •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
- •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.
- •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
研究组 & 干预措施
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.
干预措施: CX-4945 (SARS-CoV-2 domain) (Drug)
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.
干预措施: Placebo (SARS-CoV-2 domain) (Drug)
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.
干预措施: CX-4945 (Influenza virus domain) (Drug)
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.
干预措施: Placebo (Influenza virus domain) (Drug)
结局指标
主要结局
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.
时间窗: Day 1 to Day 29
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
次要结局
- The Percentage of Subjects With All Cause Hospitalization, Emergency Room Visits, or Death During Study Period.(Day 1 to Day 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(Day 1 to Day 5/7, 15, and 29)
- The Percentage of Subjects With Improved Pulmonary X-ray Findings for Pneumonia, Relative to Baseline or Showing a Return to Normalcy(Baseline to Day 5/7)
- Change From Baseline in SpO2/FiO2 Ratio(Day 1 to Day 5/7, 15, and 29)
- 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)(Day 1 to Day 5/7)
- 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(Day 1 to Day 5/7, 15, and 29)