Phase II Investigator-Initiated Clinical Trial to Investigate the Efficacy and Safety of T-705 Injection (Favipiravir) in Combination with Oseltamivir for Influenza

JRCT ID: jRCT2031240586

Registered date:27/12/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Influenza
• Date of first enrollment: 17/01/2025
• Target sample size: 80
• Study type: Interventional

Intervention(s)

The protocol treatment will commence on the registration date. The treatment period (administration period) will be 5 days.

Experimental Group:
In addition to the concomitant medication (oseltamivir phosphate) administered as 75 mg of oseltamivir twice daily for 5 days, the investigational drug (T-705IV) will be administered as follows:
On Day 1: 1600 mg once daily.
On Days 2-5: 600 mg once daily.
The investigational drug will be dissolved in normal saline to prepare an infusion solution. The solution will be administered intravenously twice daily, over approximately 60 minutes. The infusion volume will be 200 mL per dose. There must be at least 4 hours between the start times of the two daily doses.

Control Group:
In addition to the concomitant medication (oseltamivir phosphate) administered as 75 mg of oseltamivir twice daily for 5 days, normal saline will be administered as a placebo in the same manner as the investigational drug.
Normal saline will be infused intravenously over approximately 60 minutes twice daily for 5 days. The infusion volume will be 200 mL per dose. The interval between the two daily doses will follow the same schedule as the investigational drug, with at least 4 hours between the start times of the two doses.

Outcome(s)

Primary Outcome

Time to Recovery from Enrollment/Randomization
[Evaluation Method]
The principal investigator or sub-investigator will use a 7-point ordinal scale for clinical evaluation. The patient's condition will be assessed daily from enrollment/randomization through Day 29 of hospitalization. The highest score representing the patient's condition on each day will be recorded as that day's value. Recovery will be defined as the point at which the patient remains in a discharge-eligible state (score 1 or 2) for three consecutive days or is discharged. The time to recovery will be calculated up to the first day on which recovery is confirmed.

Secondary Outcome

Clinical Evaluation Items

(1) Percentage of Patients Over 29 Days Based on a 7-Point Scale
[Evaluation Method]
The principal investigator or sub-investigator will use a 7-point scale for clinical evaluation. From enrollment/randomization through Day 29 of hospitalization, the highest score for each day will be recorded. The percentage of patients according to the 7-point scale will be calculated daily until Day 29.

(2) Worsening Rate Over 15 Days and 29 Days Based on a 7-Point Scale
[Evaluation Method]
The investigator will use a 7-point scale. From enrollment/randomization through Day 29 of hospitalization, the highest score for each day will be recorded. Worsening is defined as a decline of at least one level from baseline. The percentage of patients who experienced worsening by Day 15 and Day 29 will be calculated.

(3) Time to Defervescence
[Evaluation Method]
The investigator will assess the patient's highest body temperature daily from enrollment/randomization through Day 29. Defervescence is defined as a temperature below 37.5 C for two consecutive days, regardless of antipyretic use. The time to first defervescence will be calculated. Evaluation after defervescence is not required.

(4) 29-Day Mortality Rate
[Evaluation Method]
The percentage of patients who died within 29 days, regardless of cause, will be calculated.

(5) 29-Day ICU Admission Rate
[Evaluation Method]
The percentage of patients admitted to intensive care units within 29 days will be calculated.

(6) 15-Day Incidence of Pneumonia Complications
[Evaluation Method]
The incidence of pneumonia requiring new antibiotic treatment within 15 days will be calculated.

Virological Evaluation Items

(1) Influenza Virus Titer (Day 1, 2, 3, 7)
[Evaluation Method]
Nasopharyngeal swab samples will be collected on Day 1, Day 2, Day 3, and Day 7. The virus titer in the sample (TCID50/mL) will be measured by a central lab. The titer will be plotted after log transformation, and the AUC over 3 days will be compared between groups. TCID50 is measured by serial dilution followed by cell culture inoculation. Infection presence is assessed by cytopathic effects and TCID50 calculated by the Karber method. Additionally, changes in titer from Day 1 and the proportion of patients below the detection limit will be evaluated.

(2) Influenza Virus RNA Levels (Day 1, 2, 3, 7)
[Evaluation Method]
Nasopharyngeal swab samples will be collected on Day 1, Day 2, Day 3, and Day 7. The RNA levels in the sample (copy/mL) will be measured by a central lab. RNA levels will be plotted after log transformation, and the AUC over 3 days will be compared between groups. Additionally, changes in RNA levels from Day 1 and the proportion of patients below the detection limit will be evaluated.

Key inclusion & exclusion criteria

• Age minimum: >= 65age old
• Age maximum: Not applicable

Include criteria

(1) Patients whose nasopharyngeal swab specimen tested positive for influenza virus by nucleic acid amplification test (NAAT) or antigen test.
(2) Patients with influenza symptoms* within 2 days of symptom onset (e.g., if symptom onset is on June 1, enrollment is possible until June 3).
(3) Patients aged 65 years or older (at the time of consent).
(4) Patients with influenza symptoms* requiring hospitalization.
(5) Patients who can understand the details of this clinical trial and are able to provide written informed consent themselves or through a legally authorized representative.
*Symptoms include: Fever, feeling of warmth, chills, cough, sore throat, nasal discharge, nasal congestion, myalgia, generalized pain, headache, fatigue, vomiting, diarrhea, dyspnea, shortness of breath, chest pain, abdominal pain, dizziness, altered consciousness, convulsions, decreased urine output, muscle weakness.

Exclude criteria

(1) Patients with coexisting respiratory viral infections other than influenza.
(2) Patients expected to die within 48 hours.
(3) Patients unable to take oral capsule formulations.
(4) Patients who have been administered anti-influenza drugs within 30 days prior to enrollment.
(5) Patients receiving treatment for severe liver dysfunction equivalent to Grade C in the Child-Pugh classification.
(6) Patients requiring regular hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
(7) Patients with a history of gout attacks or with uric acid levels exceeding the reference range.
(8) Patients with hereditary xanthinuria.
(9) Patients diagnosed with hypouricemia (less than 1 mg/dL) or a history of xanthine urolithiasis.
(10) Patients with a history of alcohol dependence or drug abuse.
(11) Patients with hypersensitivity to concomitant medication (oseltamivir phosphate).
(12) Patients with hypersensitivity to favipiravir.
(13) Pregnant or lactating patients or patients who may be pregnant.
(14) Premenopausal female patients who are unable to use contraceptive methods such as oral contraceptives, intrauterine devices, or barrier methods (e.g., diaphragm, condom) or combine these methods from the start of the investigational drug administration until 10 days after the end of the administration.
(15) Patients who have received any investigational drug within the past 90 days.
(16) Patients deemed by the principal investigator or sub-investigator to be unsuitable for appropriate efficacy evaluation or adverse event assessment due to underlying diseases (e.g., advanced dementia) or complications.

Related Information

• Primary Sponsor: Ohmagari Norio
• Source(s) of Monetary Support: AMED (Japan Agency for Medical Research and Development)