Study of ZSP1273 in Patients With Acute Uncomplicated Influenza A

Influenza A Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study of ZSP1273 in Adults With Acute Uncomplicated Influenza A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04024137
• Other study ID #: ZSP1273-18-02
• Status: Completed
• Phase: Phase 2
• Start date: December 7, 2019
• Est. completion date: May 18, 2020

Study information

• Verified date: December 2019
• Source: Guangdong Raynovent Biotech Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the antiviral effect, as measured by the time to alleviation of influenza symptoms and viral titer in nasopharyngeal secretions in adults with acute uncomplicated influenza A following administration of ZSP1273.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: May 18, 2020
• Est. primary completion date: May 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males and female subjects between 18-65 years (Both inclusive).

2. Patients with a diagnosis of influenza virus A infection confirmed by all of the following:

• Positive Rapid Antigen Test (RAT) with throat swabs;and

• Fever=38.0ºC (axillary) in the predose examinations;and

• At least one of the following general systemic symptoms and respiratory symptoms respectively associated with influenza are present with a severity of moderate or greater:

• General systemic symptoms:Headache,Feverishness or chills,Muscle or joint pain,Fatigue;

• Respiratory symptoms:Cough,Sore throat,Nasal congestion.

3. The time interval between the onset of symptoms and the enrollment is=48 hours. The onset of symptoms is defined as:

• Time of the first increase in body temperature(axillary temperature=38.0ºC),or

• Time when the patient experiences at least one general or respiratory symptom.

4. Subjects who agree to use an appropriate method of contraception during the study and up to 6 months after drug withdrawal.

5. Signature of a dated Informed Consent Form (ICF) indicating that the subject has been informed of all the relevant aspects(including adverse events) of the trial prior to enrollment.

Exclusion Criteria:

1. Known hypersensitivity and/or allergy to some drugs and food,especially for the composition that is similar to ZSP1273;

2. Dysphagia or any medical history in gastrointestinal that interferes with the absorption of drugs.

3. Use of the following medications within 7 days prior to screening:

• Influenza antiviral medication:oseltamivir,peramivir,famivir,abidol,amantadine or rimantadine.

• Chinese patent medicine or herbal medicine with antiviral effect.

4. Patients who have received influenza vaccine within 6 months prior to enrollment.

5. Presence of clinically significant abnormalities in ECG .

6. Chest X - ray examination confirmed bronchitis,pneumonia,pleural effusion or pulmonary interstitial lesions.

7. Patients who have experienced respiratory tract infection,Otitis media,nasosinusitis.

8. White blood cells(WBC)>10.0×109/L at screening.

9. Subject who produces purulent sputum or has suppurative tonsillitis.

10. 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.

11. Immunodeficiency,including malignant tumor,organ or marrow transplant,human immunodeficiency virus [HIV] infection,or patients receiving immunosuppressant therapy 3 months prior to enrollment.

12. Concomitant therapy with aspirin or salicylic acid.

13. Morbid obesity(Body mass index [BMI]=30kg/m2).

14. Known history of alcohol abuse or drug abuse.

15. 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.

16. Have received any other investigational products within 3 months prior to dosing.

17. Subjects who should not be included in the study in the opinion of the Investigator.

Related Conditions & MeSH terms

• Influenza A
• Influenza, Human

Intervention

Drug:
• ZSP1273 200 mg
1 X 200-mg tablet taken orally
• Placebo
2 tablets taken orally
• ZSP1273-400 mg
2 X 200-mg tablet taken orally
• Placebo
1 tablet taken orally
• ZSP1273-600 mg
3 X 200-mg tablet taken orally
• Placebo
3 tablets taken orally
• Placebo
Subjects will receive matching placebo of ZSP1273

Locations

Country	Name	City	State
China	Beijing Ditan Hospital Capital Medical University	Beijing	Beijing
China	Beijing Luhe Hospital,Capital Medical University	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Chengdu Fifth People's Hospital	Chengdu	Sichuan
China	Dongguan people's Hospital	Dongguan	Guangdong
China	Nanfang Hospital,South Medical Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital Of Guangzhou Medical University	Guangzhou	Guangdong
China	Traditional Chinese Medicine Hospital of Guangdong Province	Guangzhou	Guangdong
China	The First Affiliated Hospital,Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital	Hangzhou	Zhejiang
China	The Second Hospital Of Anhui Medical University	Hefei	Anhui
China	Huizhou Municipal Central Hospital	Huizhou	Guangdong
China	Jieyang People's Hospital	Jieyang	Guangdong
China	Jiujiang University Hospital	Jiujiang	Jiangxi
China	Linyi People's Hospital	Linyi	Shandong
China	The First Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	Sir Run Run Hospital Nanjing Medical University	Nanjing	Jiangsu
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Shenzhen People's Hospital	Shenzhen	Guangdong
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	General Hospital, Tianjin Medical University	Tianjin	Tianjin
China	Zhongshan Hospital Xiamen University	Xiamen	Fujian
China	Affiliated Hospital Of Guangdong Medical University	Zhanjiang	Guangdong
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	The Sixth People's Hospital Of Zhengzhou	Zhengzhou	Henan

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 influenza symptoms in participants	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 7 influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours	Initiation of study treatment (Day 1) up to Day 15
Secondary	AUC of the log10 pharyngeal viral load	Area under the curve (AUC) of the log10 pharyngeal viral load is measured by viral culture and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).	Days 6
Secondary	Change in the total score of 7 influenza symptoms	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(Sum of symptom scores) as assessed by the participant, and ranges from 0 to 21.	Up to Day15
Secondary	Time to alleviation of each influenza symptom.	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 Day15
Secondary	Time to Resolution of Fever	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.	Up to Day15
Secondary	Proportion of patients reporting normal temperature	Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment.	Up to Day15
Secondary	Percentage of subjects with virus titer detected	Influenza virus RNA was quantified from throat swabs.Proportion of patients positive for influenza virus titer is defined as the percentage of patients whose virus titer is not less than the lower limit of quantification among those assessed for virus titer measured by viral culture and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on Days 2,4, 6.	Days 2,4, 6
Secondary	Duration of detectable virus	Defined as the time from the start of treatment to the time when the titer is less than the lower limit of quantification measured by viral culture and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).	Days 2,4, 6
Secondary	Change in virus titer	Defined as the change from baseline in virus titer measured by viral culture and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).	Days 2,4, 6
Secondary	Change in viral RNA load	Defined as the change from baseline in viral RNA load measured by viral culture and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on Days 2, 4, 6.	Days 2,4, 6
Secondary	Incidence of influenza-related complications	Defined as the percentage of subjects in the analysis population who experience each influenza-related complication (sinusitis, otitis media, bronchitis, and pneumonia) as an adverse event after the initiation of the study treatment.	Up to Day21
Secondary	Time to return to normal activities of daily life	Participants were asked to record their activities of daily life on a scale from 0 (worst possible health) to 10 (normal activities of daily life).; Time to return to normal activities of daily life 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 Day15
Secondary	Proportion of patients with the Serological conversion of neutralizing antibody titer relative to that in Visit 1 =4	Defined as the protprtion of patients with a ratio of 4 or more at Visit 5 antibody titer relative to Visit 1 titer	Baseline and Day 21
Secondary	Proportion of patients and frequency in combination use of acetaminophen.	The proportion of patients who use acetaminophen in the duration of the study	Up to 21 days post-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.	Baseline up to Day 15