A Study of ZSP1273 Tablets in Patients With Acute Uncomplicated Influenza A

Influenza A Clinical Trial

Official title:

A Randomized, Double-blind Phase III Clinical Study of ZSP1273 Tablets Compared With Placebo or Oseltamivir Patients With Acute Uncomplicated Influenza A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04683406
• Other study ID #: ZSP1273-20-06
• Status: Completed
• Phase: Phase 3
• Start date: December 28, 2020
• Est. completion date: May 16, 2023

Study information

• Verified date: June 2023
• Source: Guangdong Raynovent Biotech Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 750
• Est. completion date: May 16, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza A
• Influenza, Human

Intervention

Drug:
• ZSP1273 600 mg
3 X 200-mg tablet taken orally
• Placebo to Oseltamivir
Placebo capsules matching oseltamivir2 X 75-mg
• Oseltamivir(oral)
2 X 75-mg tablet taken orally
• Placebo to ZSP1273
Placebo capsules matching ZSP1273 600 mg

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital,Capital Medical University	Beijing	Beijing
China	Beijing Ditan Hospital Capital Medical University	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	The First Affiliated Hospital of bengbu medical college	Bengbu	Anhui
China	Binzhou Medical University Hospital	Binzhou	Shandong
China	The First Hospital Of Jilin University	Changchun	Jilin
China	Chengdu Xinhua Hospital	Chengdu	Sichuan
China	General Hospital of Western Theater of PLA	Chengdu	Sichuan
China	Sichuan Provicial People's Hospital	Chengdu	Sichuan
China	The Third People's Hospital of Wuhou, Chengdu	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	People's Hospital of Cuanjiang, Chongqing	Chongqing	Chongqing
China	Third Military Medical University	Chongqing	Chongqing
China	Dazhou Central Hospital	Dazhou	Sichuan
China	Dongguan People's Hospital	Dongguan	Guangdong
China	Foshan First People's Hospital	Foshan	Guangdong
China	Shunde University of Southern Medical University	Foshan	Guangdong
China	First Affiliated Hospital of Gannan Medical University	Ganzhou	Jiangxi
China	Guangdong Province Traditional Chinese Medical Hospital	Guangzhou	Guangdong
China	Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital Of Guangzhou Medical University	Guangzhou	Guangdong
China	Guizhou Provicial People's Hospital	Guiyang	Guizhou
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Heze Municipal Hospital	Heze	Shandong
China	Huaihe Hospital of Henan University	Huaihe	Henan
China	Huizhou Central People's Hospital	Huizhou	Guangdong
China	Jieyang People's Hospital	Jieyang	Guangdong
China	Jinan Central Hospital	Jinan	Shandong
China	Jiujiang University Affiliated Hospital	Jiujiang	Jiangxi
China	The first People hospital of Yunnan Province	Kunming	Yunnan
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Linyi People's Hospital	Linyi	Shandong
China	Luoyang Central Hospital Affiliated To Zhengzhou University	Luoyang	Henan
China	First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Second Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	The Third Hospital Of Nanchang	Nanchang	Jiangxi
China	Affiliated Hospital of North Sichuan College	Nanchong	Sichuan
China	Nanjing First Hospital	Nanjing	Jiangsu
China	Nanjing Jiangning Hospital	Nanjing	Jiangsu
China	Sir run run Hospital Nanjing Medical University	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Nanning First People's Hospital	Nanning	Guangxi
China	Nanyang Central Hospital	Nanyang	Henan
China	Nanyang First People's Hospital	Nanyang	Henan
China	The Second People's hospital of Nanyang	Nanyang	Henan
China	The Third Affiliated Hospital of Nanyang Medical College	Nanyang	Henan
China	General Hospital of Liaohe Oilfield	Panjin	Liaoning
China	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	Qingyuan People's Hospital	Qingyuan	Guangdong
China	First Hospital of Qinhuangdao	Qinhuangdao	Hebei
China	Quanzhou First Hospital	Quanzhou	Fujian
China	Ruian People's Hospital	Ruian	Zhejiang
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shangyao People's Hospital	Shangyao	Jiangxi
China	Shantou Central Hospital	Shantou	Guangdong
China	Yuebei People's Hospital	Shaoguan	Guangdong
China	Shenyang Central Hospital Affiliated To Shenyang medical college	Shenyang	Liaoning
China	Shenzhen Luohu Hospital Group Luohu People's Hospital	Shenzhen	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	Songgang People's Hospital	Shenzhen	Guangdong
China	Shanxi Bethune Hospital	Taiyuan	Shanxi
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Fujian Provincal Hospital	Xiamen	Fujian
China	Xiamen Hospital of T.C.M	Xiamen	Fujian
China	Xiamen Zhongshan Hospital	Xiamen	Fujian
China	The Third Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	Xuancheng People's Hospital	Xuancheng	Anhui
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Yiyang Central hospital	Yiyang	Hunan
China	Shandong Energy Zaozhuang Mining	Zaozhuang	Shandong
China	Henan Provicial People's Hospital	Zhengzhou	Henan
China	Zhengzhou Central Hospital	Zhengzhou	Henan
China	Zhengzhou Sixth Hospital	Zhengzhou	Henan
China	PKUCare luzhong Hospital	Zibo	Shandong
China	Affiliated Hospital Zunyi Medical College	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Raynovent Biotech Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours.; Time to alleviation of symptoms was analyzed using the Kaplan-Meier(KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point	Up to 14 days after first dose
Primary	Time to Alleviation of Symptoms in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours.; Time to alleviation of symptoms was analyzed using the Kaplan-Meier(KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point	Up to 14 days after first dose
Secondary	Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Virus titer was quantified from nasopharyngeal swabs by tissue culture methods.	Days 2, 4, 6
Secondary	Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Virus titer was quantified from nasopharyngeal swabs by tissue culture methods.	Days 2, 4, 6
Secondary	Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs.	Days 2, 4, 6
Secondary	Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs.	Days 2, 4, 6
Secondary	Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Virus titer was quantified from nasopharyngeal swabs.	Days 2, 4, 6
Secondary	Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Virus titer was quantified from nasopharyngeal swabs.	Days 2, 4, 6
Secondary	Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Nasopharyngeal swabs were obtained for viral quantitation.	Days 2, 4, 6
Secondary	Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Nasopharyngeal swabs were obtained for viral quantitation.	Days 2, 4, 6
Secondary	Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Placebo	This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 5. AUC was calculated using the trapezoidal method	Up to 6 days after first dose
Secondary	Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir	This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 5. AUC was calculated using the trapezoidal method	Up to 6 days after first dose
Secondary	Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP-1273 or Placebo		Up to 6 days after first dose
Secondary	Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to ZSP1273 or Oseltamivir		Up to 6 days after first dose
Secondary	Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Placebo		Up to 6 days after first dose
Secondary	Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to ZSP1273 or Oseltamivir		Up to 6 days after first dose
Secondary	Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1)	Up to 14 days after first dose
Secondary	Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1)	Up to 14 days after first dose
Secondary	Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.; Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point.	Up to 14 days after first dose
Secondary	Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.; Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point.	Up to 14 days after first dose
Secondary	Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours; Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point	Up to 14 days after first dose
Secondary	Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours; Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point	Up to 14 days after first dose
Secondary	Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms); The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant at each time point	Up to 14 days after first dose
Secondary	Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms); The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant at each time point	Up to 14 days after first dose
Secondary	Time to Resolution of Fever in Participants Randomized to ZSP1273 or Placebo	Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours; Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point	Up to 14 days after first dose
Secondary	Time to Resolution of Fever in Participants Randomized to ZSP1273 or Oseltamivir	Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours; Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point	Up to 14 days after first dose
Secondary	Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Placebo	Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment	Up to 14 days after first dose
Secondary	Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to ZSP1273 or Oseltamivir	Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment	Up to 14 days after first dose
Secondary	Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Placebo	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.	Up to 14 days after first dose
Secondary	Time to Alleviation of Individual Symptoms in Participants Randomized to ZSP1273 or Oseltamivir	Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms).; Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.	Up to 14 days after first dose
Secondary	Time to Return to Preinfluenza Health Status in Participants Randomized to ZSP1273 or Placebo		Up to 14 days after first dose
Secondary	Time to Return to Preinfluenza Health Status in Adults Randomized to ZSP1273 or Oseltamivir	Defined as the time between the initiation of the study treatment and the return to normal activities of daily life. The return to normal activities of daily life is defined as the time when the subject assesses his/her activities as 10.Subjects with a baseline self-rated daily activity score of 10 are not included in this analysis.	Up to 14 days after first dose
Secondary	Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Placebo	Defined as the time between the initiation of the study treatment and the return to normal activities of daily life. The return to normal activities of daily life is defined as the time when the subject assesses his/her activities as 10.Subjects with a baseline self-rated daily activity score of 10 are not included in this analysis.	Up to 14 days after first dose
Secondary	Percentage of Participants With Influenza-related Complications in Participants Randomized to ZSP1273 or Oseltamivir		Up to 14 days after first dose
Secondary	Change in EQ-5D-5L	Defined as the change from baseline in the index value and that in EQ VAS score as calculated from the EQ-5D-5L questionnaire.	Up to 14 days after first dose