Clinical trial NCT06573008: Study of GP681 Tablets Compared With Placebo in Patients With Influenza at High Risk of Influenza Complications
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study on the Safety and Efficacy of GP681 Tablets in Patients With Influenza at High Risk of Influenza Complications
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Influenza, Human
Lead sponsor: Jiangxi Qingfeng Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-27
Enrollment: 328
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and population pharmacokinetics of a single, oral dose of GP681 compared with placebo in patients aged 12 and older With Influenza at High Risk of Influenza Complications.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged ≥12 years at the time of signing the informed consent form.
2. Patients with a diagnosis of influenza confirmed by all of the following:

   * Positive throat or nose swab by rapid influenza antigen test (RAT) (where rapid influenza virus nucleic acid test or other rapid molecular diagnostic methods are also acceptable);

     * Fever (axillary temperature ≥37.3℃) in the predose examinations or \> 4 hours after dosing of antipyretics if they were taken;

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

   Systemic symptoms: headache, fever or chills, muscle or joint aches, fatigue; Respiratory system symptoms: cough, sore throat, nasal congestion.
3. The time interval between the onset of symptoms and random enrollment is 48 hours or less. The onset of symptoms is defined as either:

   1. Time of the first increase in body temperature (axillary temperature ≥37.3℃)
   2. Time when the patient experiences at least 1 new general or respiratory symptom related to influenza
4. Referring to the standards of the Centers for Disease Control and Prevention (CDC) in the United States and the definition of high-risk populations for influenza complications in the "Expert Consensus on Diagnosis and Treatment of Influenza in Adults in the Emergency Department (2022 Edition)", that is, if at least one of the following criteria is met, the patient will be considered at high risk of influenza complications:

   1. Asthma or chronic lung diseases \[such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, chronic bronchitis, bronchiectasis, emphysema, chronic interstitial pneumonia, etc.\];
   2. Endocrine disorders (including diabetes);
   3. Residents of long-term care institutions (such as nursing homes);
   4. Immune system impairment (including patients receiving chronic systemic corticosteroid treatment of ≤20mg/d prednisone or an equivalent dose);
   5. Neurological and neurodevelopmental disorders (including brain, spinal cord, peripheral nerve and muscle diseases, such as cerebral palsy, epilepsy (episodic disorders), stroke, muscular dystrophy or spinal cord injury);
   6. Heart diseases (such as congenital heart disease, congestive heart failure, or coronary artery disease), but not including hypertension without any other cardiac-related symptoms;
   7. Patients aged ≥65 years;
   8. Blood system diseases (such as sickle cell disease);
   9. Metabolic system diseases (such as hereditary metabolic diseases and mitochondrial diseases);
   10. Liver diseases (such as chronic hepatitis B, chronic hepatitis C, non-alcoholic steatohepatitis);
   11. Kidney diseases (estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m2 by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula);
   12. Obese patients (BMI ≥ 30 kg/m2);
   13. Female patients within 2 weeks postpartum and not breastfeeding.
5. Subjects of child-bearing potential who agree to use a highly effective method of contraception for 1 month after drug withdrawal.
6. Subjects and/or their guardian who are willing to provide written informed consent and consent to participate in the study, able to understand the study and comply with all study procedures, including patient health diary records.

Exclusion Criteria:

1. History of allergic reactions attributed to GP681,Acetaminophen, bromohexine hydrochloride or any of the ingredients of its formulation.
2. Known history of dysphagia or any gastrointestinal disease that affects drug absorption (including but not limited to chronic diarrhea, inflammatory bowel disease, tuberculosis of the intestines, gastrinoma, short bowel syndrome, postoperative gastrectomy, etc.);
3. Screening patients who, in the opinion of the investigator, require hospitalization due to severe influenza virus infection;.
4. Screening patients who, at the time of screening, are clinically diagnosed with bacterial or other viral infections requiring systemic antibacterial or antiviral treatment;
5. Cancer patients who are currently receiving or have received chemotherapy or radiation therapy within the past year (excluding non-melanoma skin cancer and thyroid cancer)
6. Known HIV-infected patients;
7. Organ or bone marrow transplant recipients;
8. Patients who are currently receiving \>20mg/d of prednisone or equivalent chronic systemic corticosteroid therapy;
9. Patients who have used anti-influenza virus drugs (including neuraminidase inhibitors, hemagglutinin inhibitors, and M2 ion channel blockers, such as oseltamivir, zanamivir, palivizumab, favipiravir, abidol, marabolexavir, amantadine or rimantadine or other anti-influenza virus drugs approved by NMPA) within the past 2 weeks or who have received influenza vaccination within the past 6 months;
10. Exclusion of participants who have received clinical research or screening within the past 30 days for any indication with a trial drug or device, or who have received clinical research for a monoclonal antibody drug for viral diseases within the past year;
11. Known to have had a previous history of severe liver function impairment such as cirrhosis with ascites, hepatic encephalopathy, or a history of upper gastrointestinal bleeding;
12. Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula \<30mL/min/1.73m2 at the time of screening;
13. Individuals with a history of alcohol abuse or substance abuse (more than 14 units of alcohol per week, 1 unit of alcohol = 360 mL of beer or 45 mL of spirits with an alcohol content of 40% or 150 mL of wine with an alcohol content of 12%);
14. Adult reproductive-age females who are pregnant or breastfeeding or who have a positive pregnancy test. Women who are infertile (i.e., women who have had a hysterectomy, bilateral oophorectomy, or tubal ligation for medical reasons or who are postmenopausal - defined as age \> 50 years and menopause has occurred for at least 2 years) do not need a pregnancy test;
15. Patients who, in the opinion of the Investigator, may not be qualified or suitable for the study.

Primary outcomes:
measure: Time to alleviation of influenza symptoms
timeFrame: up to Day 15
Secondary outcomes:
measure: Change From Baseline in Virus RNA (Q-PCR) at Each Time Point
timeFrame: Day 2, Day3, Day5, Day7
measure: Percentage of Participants With Positive Influenza Virus RNA by Q-PCR at Each Time Point
timeFrame: Day 2, Day3, Day5, Day7
measure: Area Under the Concentration (AUC) of virus RNA by Q-PCR and AUC of virus titer
timeFrame: Up to Day 7
measure: Change in the total score of 7 influenza symptoms
timeFrame: Up to Day15
measure: Time to Cessation of Viral Shedding Determined by Virus Titer
timeFrame: up to Day7
measure: Time to alleviation of each influenza symptom.
timeFrame: Up to Day15
measure: Time to Alleviation of the Three Respiratory Symptoms in Participants
timeFrame: Up to Day15
measure: Time to Alleviation of the Four Systemic Symptoms in Participants
timeFrame: Up to Day15
measure: Percentage of Participants Reporting Normal Temperature at Each Time Point
timeFrame: 12h, 24h,48h,72h,96h,120h,144h,168h
measure: Time to Resolution of Fever
timeFrame: Up to Day15
measure: Incidence of influenza-related complications
timeFrame: Up to Day15
measure: Proportion of patients and frequency in combination use of acetaminophen.
timeFrame: Up to Day15
measure: The percentage of participants who received systemic antibiotics.
timeFrame: Up to Day15
measure: The percentage of participants with secondary influenza infections after enrollment
timeFrame: Up to Day15
measure: Time to Return to Preinfluenza Health Status
timeFrame: Up to Day15
Other outcomes:
Locations:
city: Chizhou
country: China
facility: The people's Hospital of Chizhou
Study officials:
References: