Influenza
Conditions
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled Phase II study to evaluate the efficacy and safety of SYH2085 tablets compared with placebo in Chinese adult participants with uncomplicated influenza. The study plans to enroll patients with typical systemic and respiratory influenza symptoms, with symptom onset ≤48 hours.
Interventions
DRUGSYH2085
One or two 40-mg SYH2085 tablets taken orally
DRUGPlacebo
One or two placebo tablets taken orally
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
multicenter, randomized, parallel-group, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at time of signing ICF. * At screening, meet all of the following: 1. Positive influenza antigen test or influenza virus nucleic acid test (other rapid molecular diagnostic methods are acceptable). 2. Axillary temperature ≥37.3°C at screening; if antipyretics have been taken, axillary temperature ≥37.3°C at least 4 hours after dosing; 3. At least one systemic influenza symptom of moderate or greater severity: muscle/joint aches, fatigue, headache, fever/chills; 4. At least one respiratory influenza symptom of moderate or greater severity: nasal congestion, sore throat, cough. * Time from onset of first influenza symptom to randomization ≤48 hours. * Female participants must meet: 1. Not of childbearing potential (i.e., hysterectomy, bilateral oophorectomy, documented ovarian failure, or postmenopausal defined as \>50 years and amenorrhea ≥12 months), or 2. Of childbearing potential, with negative pregnancy test at screening, and not pregnant, peripartum, or breastfeeding. * Participants and their partners agree to complete abstinence or use effective contraception from screening until 1 month after study completion. * Male participants agree not to donate sperm from screening until 1 month after study completion. * Understand and voluntarily sign ICF, willing and able to comply with all study procedures, and able to complete the participant diary as required.
Exclusion criteria
* Influenza virus infection requiring hospitalization (any of the following): 1. Significant exacerbation of underlying diseases, e.g., COPD, diabetes, chronic heart failure, chronic renal failure, cirrhosis, etc. 2. Any of the following severe case criteria: 1. Respiratory rate ≥30/min; 2. Oxygen saturation ≤93% on room air at rest; 3. PaO2/FiO2 ≤300; for high-altitude areas (\>1000 m), correction: PaO2/FiO2 × \[760/atmospheric pressure (mmHg)\] (1 mmHg=0.133 kPa); 4. Progressive clinical deterioration with lung imaging showing \>50% lesion progression within 24-48 hours. 3. Any critical case criteria: 1. Respiratory failure requiring mechanical ventilation; 2. Shock; 3. Acute necrotizing encephalopathy; 4. Other organ failure requiring ICU monitoring. * High-risk groups for severe/critical cases (any of the following): 1. Severe or poorly controlled underlying diseases, e.g., COPD, liver disease (ALT or AST ≥3×ULN, total bilirubin ≥1.5×ULN), chronic kidney disease (serum creatinine \>177 μmol/L or 2 mg/dL), severe hematological disorders, chronic congestive heart failure (NYHA class III-IV), neurological and neuromuscular diseases, metabolic diseases, etc.; 2. Clinically significant corrected QT interval abnormality on ECG (QTc \>450 ms for males or \>470 ms for females, QTcF by Fridericia formula); 3. Immunocompromised patients, e.g., malignancy, organ or bone marrow transplantation, HIV infection, or use of immunosuppressants within 3 months; Note: Participants with basal cell carcinoma, localized squamous cell carcinoma of skin, or cervical carcinoma in situ may be enrolled if curative treatment completed ≥12 months before ICF; other malignancies if curative treatment completed ≥5 years before ICF. 4. Concurrent conditions requiring aspirin or salicylate therapy; 5. Obesity (BMI \>30 kg/m²). * Bronchitis, pneumonia, pleural effusion, or interstitial lung disease suspected by a clinician at screening, or confirmed by chest imaging (X-ray / CT) and judged by investigator at screening. * Acute respiratory infection, otitis media, or sinusitis within 2 weeks before screening. * Concurrent infection requiring systemic anti-infective therapy, or WBC \>10.0×10⁹/L at screening. * Purulent sputum or suppurative tonsillitis. * Difficulty swallowing medication or history of gastrointestinal diseases that significantly affect drug absorption (including but not limited to reflux esophagitis, chronic diarrhea, inflammatory bowel disease, intestinal tuberculosis, gastroinoma, short-bowel syndrome, post-gastrectomy, etc.). * History of allergy to active ingredient or excipients of the study drug. * Previous exposure to SYH2085. * Body weight \<40 kg. * Use of anti-influenza drugs within 7 days before screening (including but not limited to neuraminidase inhibitors, hemagglutinin inhibitors, M2 ion channel blockers, and CEN inhibitors, e.g., oseltamivir, zanamivir, peramivir, laninamivir, umifenovir, favipiravir, rimantadine, amantadine, arbidol, nitazoxanide, baloxavir marboxil, marboxil, etc.). * Influenza vaccination within 6 months before screening. * History of alcohol abuse within 3 months before screening (males \>14 units/week, females \>7 units/week; 1 unit = 10 g pure alcohol), or alcohol consumption within 48 hours before dosing, or history of drug abuse. * Use of any prohibited medications within 2 weeks / 5 half-lives (whichever longer; excluding anti-influenza drugs) before screening and during the planned trial period. * Participation in any clinical trial of investigational drug, biologic, or medical device within 30 days (or 5 half-lives, whichever longer) before screening. * Positive SARS-CoV-2 antigen or nucleic acid test. * Any other condition judged by the investigator as unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to resolution of all influenza symptoms (hours) | Up to Day22 | Time to resolution of all influenza symptoms (hours) is defined as the time from start of study treatment to resolution of all influenza symptoms. Resolution of all influenza symptoms. is defined as all 7 influenza symptoms (headache, fever/chills, muscle/joint aches, fatigue, cough, nasal congestion, sore throat) rated as 2 or 3 becoming 0 (absent) or 1 (mild), and all clinical symptoms rated as 0 or 1 remaining resolved; with duration of resolution at least 21.5 hours (approximately 24 hours minus 10%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with adverse events (AEs) | Up to Day22 | Any abnormalities in vital signs, physical examinations, laboratory tests, 12-lead electrocardiograms (ECGs), or other parameters observed in participants post-dose will be recorded as AEs. |
| Pharmacokinetics (plasma concentrations) | Up to Day22 | Plasma concentrations of SYH2085 active metabolite SYH2085A-01207 will be measured. |
| Pharmacokinetics (Cmax) | Up to Day22 | The pharmacokinetics parameters Cmax will be calculated. |
| Pharmacokinetics (AUC0-t) | Up to Day22 | The pharmacokinetics parameters AUC0-t will be calculated. |
| Pharmacokinetics (AUC0-∞) | Up to Day22 | The pharmacokinetics parameters AUC0-∞ will be calculated. |
| Pharmacokinetics (Tmax) | Up to Day22 | The pharmacokinetics parameters Tmax will be calculated. |
| Pharmacokinetics (CL/F) | Up to Day22 | The pharmacokinetics parameters CL/F will be calculated. |
| Pharmacokinetics (Vz/F) | Up to Day22 | The pharmacokinetics parameters Vz/F will be calculated. |
| Pharmacokinetics (t1/2) | Up to Day22 | The pharmacokinetics parameters t1/2 will be calculated. |
| Change from baseline in influenza virus RNA (log10 copies/mL) and virus titer (log10 TCID50/mL) at each visit | Up to Day22 | Nasopharyngeal swabs will be collected from participants at the study center and sent to the central laboratory for quantitation of viral RNA load and viral titer. |
| Time to influenza virus RNA negativity (hours) | Up to Day22 | Time to influenza virus RNA negativity (hours) is defined as time from start of study treatment to first influenza virus RNA below the lower limit of detection (by RT-PCR). |
| Time to influenza virus titer negativity (hours) | Up to Day22 | Time to influenza virus titer negativity (hours) is defined as time from start of study treatment to first virus titer below the lower limit of quantification. |
| Change from baseline in influenza virus RNA (log10 copies/mL) at each visit | Up to Day22 | Nasopharyngeal swabs will be collected from participants at the study center and sent to the central laboratory for quantitation of viral RNA load. |
| Change from baseline in influenza virus and virus titer (log10 TCID50/mL) at each visit | Up to Day22 | Nasopharyngeal swabs will be collected from participants at the study center and sent to the central laboratory for quantitation of viral titer. |
| Viral load AUC and virus titer AUC | Up to Day22 | Viral load AUC is defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 22. Virus titer AUC is defined as AUC of change from baseline in the virus titer from Day 1 to Day 22. |
| Percentage of participants with RT-PCR-positive influenza virus RNA and detectable virus titer at each visit (%) | Up to Day22 | RT-PCR-positive influenza virus RNA is defined as the amount of virus RNA not less than the lower limit of detection (by RT-PCR); detectable virus titer is defined as virus titer not less than the lower limit of quantification. |
| Percentage of participants with resolution of all influenza symptoms at each visit (%) | Up to Day22 | Resolution of all influenza symptom is defined as all 7 influenza symptoms (headache, fever/chills, muscle/joint aches, fatigue, cough, nasal congestion, sore throat) rated as 2 or 3 becoming 0 (absent) or 1 (mild), and all clinical symptoms rated as 0 or 1 remaining resolved; with duration of resolution at least 21.5 hours (approximately 24 hours minus 10%). |
| Time to resolution of 4 systemic symptoms (headache, fever/chills, muscle/joint aches, fatigue) (hours) | Up to Day22 | Time to resolution of 4 systemic symptoms is defined as the time from start of study treatment to resolution of 4 systemic symptoms. |
| Time to resolution of 3 respiratory symptoms (cough, nasal congestion, sore throat) (hours) | Up to Day22 | Time to resolution of 3 respiratory symptoms is defined as the time from start of study treatment to resolution of 3 respiratory symptoms. |
| Time to resolution of each influenza symptom (hours) | Up to Day22 | Time to resolution of each influenza symptoms is defined as the time from the start of treatment to resolution of the influenza symptoms. |
| Change from baseline in composite influenza symptom score at each visit | Up to Day22 | The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participants, and ranges from 0 to 21. |
| Time to resolution of fever (hours) | Up to Day22 | Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. |
| Percentage of participants reporting normal temperature at each visit (%) | Up to Day22 | Participants reporting normal temperature is defined as those with axillary temperature dropping to less than 37°C after the initiation of study treatment. |
| Body temperature at each visit (°C) | Up to Day22 | Body temperature will be self-measured and recorded by participants every daily. |
| Percentage of participants using concomitant acetaminophen (%) and frequency of use | Up to Day22 | Acetaminophen will be provided as a rescue medication. If the investigator determines that the participant's influenza symptoms require treatment with acetaminophen, the participant should record the time and dose of administration. |
| Percentage of influenza-related complications (hospitalization, death, sinusitis, bronchitis, otitis media, and radiologically confirmed pneumonia) (%) | Up to Day22 | Participants will be assessed by the investigations prior to dosing and during the study period. |
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed