Clinical trial NCT04683406: A Study of ZSP1273 Tablets in Patients With Acute Uncomplicated Influenza A
Official title: A Randomized, Double-blind Phase III Clinical Study of ZSP1273 Tablets Compared With Placebo or Oseltamivir Patients With Acute Uncomplicated Influenza A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza A
Lead sponsor: Guangdong Raynovent Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-12-24
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, placebo-controlled, and active controlled clinical trial to assess the efficacy and safety of ZSP1273 tablets in the treatment of Acute Uncomplicated influenza A.


Eligibility criteria: Inclusion Criteria:

1. Patients who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the predose examinations appropriately.
2. Male or female patient s aged ≥ 18 to ≤ 64 years at the time of signing the informed consent/assent form
3. Patients with a diagnosis of influenza virus infection confirmed by all of the following

   * Positive Rapid Antigen Test (RAT) with throat swabs;and
   * Fever ≥ 38ºC (axillary) in the predose examinations or \> 4 hours after dosing of antipyretics if they were taken;and
   * At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater I. Headache II. Feverishness or chills III. Muscle or joint pain IV. Fatigue
   * At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater I. Cough II. Sore throat III. Nasal congestion
4. The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either

   * Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature)
   * Time when the patient experiences at least one general or respiratory symptom
5. Women of childbearing potential (WOCBP) who agree to use a highly effective method of contraception for 3 months after the first dose of ZSP1273 or oseltamivir

Exclusion Criteria:

1. Patients with severe influenza virus infection requiring inpatient treatment
2. Patients aged ≥ 18 years with known allergy to oseltamivir (Tamiflu) or ZSP1273
3. Patients unable to swallow tablets or capsules or any medical history in gastrointestinal that interferes with the absorption of drugs
4. Patients who have received antiviral medication including peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 7 days prior to the predose examinations
5. Patients who have received Chinese patent medicine or herbal medicine with antiviral effect within 7 days prior to the predose examinations
6. Patients who have received Anti-influenzal prescription within 7 days prior to the predose examinations
7. Subject who produces purulent sputum or has suppurative tonsillitis.
8. White blood cells(WBC)\>10.0×109/L at screening.
9. Chest X - ray examination confirmed bronchitis,pneumonia,pleural effusion or pulmonary interstitial lesions.
10. Patients who have experienced respiratory tract infection,Otitis media,nasosinusitis.
11. Patients with severe or uncontrollable underlying diseases:blood disorders,severe chronic obstructive pulmonary disease(COPD),liver disorders(ALT or AST≥3 ULN,total bilirubin≥1.5 ULN),kidney disorders(serum creatinine\>177μmol/L or 2mg/dL),chronic congestive heart failure(NYHA III-IV),mental disorders
12. Immunodeficiency,including malignant tumor,organ or marrow transplant,human immunodeficiency virus \[HIV\] infection,or patients receiving immunosuppressant therapy 3 months prior to enrollment.
13. Concomitant therapy with aspirin or salicylic acid.
14. Patients weighing \< 40 kg or morbid obesity(Body mass index \[BMI\]≥30kg/m2)
15. Known history of alcohol abuse or drug abuse
16. Pregnancy or breastfeeding at screening and during the study.All female subjects of childbearing potential must have a negative urine pregnancy test at screening and during the trial.
17. Have received any other investigational products within 3 months prior to dosing.
18. Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions

Primary outcomes:
measure: Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
Secondary outcomes:
measure: Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Days 2, 4, 6
measure: Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Days 2, 4, 6
measure: Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Days 2, 4, 6
measure: Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Days 2, 4, 6
measure: Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Days 2, 4, 6
measure: Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Days 2, 4, 6
measure: Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Days 2, 4, 6
measure: Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Days 2, 4, 6
measure: Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 6 days after first dose
measure: Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 6 days after first dose
measure: Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP-1273 or Placebo
timeFrame: Up to 6 days after first dose
measure: Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 6 days after first dose
measure: Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 6 days after first dose
measure: Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 6 days after first dose
measure: Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Time to Resolution of Fever in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Resolution of Fever in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Time to Return to Preinfluenza Health Status in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Time to Return to Preinfluenza Health Status in Adults Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Placebo
timeFrame: Up to 14 days after first dose
measure: Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Oseltamivir
timeFrame: Up to 14 days after first dose
measure: Change in EQ-5D-5L
timeFrame: Up to 14 days after first dose
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of bengbu medical college
state: Anhui
city: Xuancheng
country: China
facility: Xuancheng People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Chaoyang Hospital,Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing Ditan Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Chongqing
country: China
facility: People's Hospital of Cuanjiang, Chongqing
state: Chongqing
city: Chongqing
country: China
facility: Third Military Medical University
state: Chongqing
city: Quanzhou
country: China
facility: Quanzhou First Hospital
state: Fujian
city: Xiamen
country: China
facility: Fujian Provincal Hospital
state: Fujian
city: Xiamen
country: China
facility: Xiamen Hospital of T.C.M
state: Fujian
city: Xiamen
country: China
facility: Xiamen Zhongshan Hospital
state: Fujian
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Foshan
country: China
facility: Foshan First People's Hospital
state: Guangdong
city: Foshan
country: China
facility: Shunde University of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Province Traditional Chinese Medical Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital Of Guangzhou Medical University
state: Guangdong
city: Huizhou
country: China
facility: Huizhou Central People's Hospital
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Shantou
country: China
facility: Shantou Central Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Luohu Hospital Group Luohu People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Songgang People's Hospital
state: Guangdong
city: Nanning
country: China
facility: Nanning First People's Hospital
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provicial People's Hospital
state: Guizhou
city: Zunyi
country: China
facility: Affiliated Hospital Zunyi Medical College
state: Guizhou
city: Qinhuangdao
country: China
facility: First Hospital of Qinhuangdao
state: Hebei
city: Huaihe
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: Luoyang Central Hospital Affiliated To Zhengzhou University
state: Henan
city: Nanyang
country: China
facility: Nanyang Central Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang First People's Hospital
state: Henan
city: Nanyang
country: China
facility: The Second People's hospital of Nanyang
state: Henan
city: Nanyang
country: China
facility: The Third Affiliated Hospital of Nanyang Medical College
state: Henan
city: Xinxiang
country: China
facility: The Third Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Provicial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Central Hospital
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou Sixth Hospital
state: Henan
city: Yiyang
country: China
facility: Yiyang Central hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Jiangning Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Sir run run Hospital Nanjing Medical University
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
state: Jiangxi
city: Jiujiang
country: China
facility: Jiujiang University Affiliated Hospital
state: Jiangxi
city: Nanchang
country: China
facility: First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Second Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Nanchang
country: China
facility: The Third Hospital Of Nanchang
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Shangyao
country: China
facility: Shangyao People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital Of Jilin University
state: Jilin
city: Panjin
country: China
facility: General Hospital of Liaohe Oilfield
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Central Hospital Affiliated To Shenyang medical college
state: Liaoning
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Heze
country: China
facility: Heze Municipal Hospital
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Zaozhuang
country: China
facility: Shandong Energy Zaozhuang Mining
state: Shandong
city: Zibo
country: China
facility: PKUCare luzhong Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Xinhua Hospital
state: Sichuan
city: Chengdu
country: China
facility: General Hospital of Western Theater of PLA
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provicial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: The Third People's Hospital of Wuhou, Chengdu
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Dazhou
country: China
facility: Dazhou Central Hospital
state: Sichuan
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan College
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Kunming
country: China
facility: The first People hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ruian
country: China
facility: Ruian People's Hospital
state: Zhejiang
Study officials:
References: