A Study to Confirm the Effectiveness and Safety of AK0529 in Treating RSV Infections in Hospitalized Infants

A Randomized, Double-blind, Placebo-controlled, Phase III Confirmatory Study to Evaluate the Efficacy, Safety, Tolerability, and Antiviral Activity of Repeated Oral Administration of AK0529 in Hospitalized Infants with Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the most common respiratory infectious pathogen recognized worldwide that poses serious health risks to infants, and an important cause of hospitalization for severe respiratory infections in infants. Serious respiratory problems such as pneumonia caused by RSV are one of the leading causes of death from respiratory diseases in infants. AK0529 targets the Pre-F (fusion) protein on the surface of the viral envelope. Specifically, it prevents the virus from invading uninfected cells and inhibits the fusion between host cells by inhibiting the fusion of the F (fusion) proteins on the surface of the RSV envelope, thus providing the effects of anti-RSV infection. This is a randomized, double-blind, placebo-controlled, multicenter, phase III clinical study to evaluate the efficacy and safety of AK0529 in hospitalized infants aged 1 to 24 months with RSV infection. Considering the benefits of AK0529 in the population with RSV infection, hospitalized infants with moderate to severe RSV infection were selected as the target population for this study.

This is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical study conducted among Chinese infants aged 1 to 24 months hospitalized with Respiratory Syncytial Virus (RSV) infection.

The study plans to enroll 180 infants aged 1 to 24 months with RSV infection. Eligible subjects will be randomized in a 1:1 ratio (AK0529: placebo). These subjects will receive the study drug twice daily for 5 consecutive days and the dose depends on subject's weight range.

Each subject in this study will undergo a visit schedule comprising a screening period of 36 hours before the first dose, a 5-day double-blinded treatment period, and a 9-day safety follow-up period after the last dose of treatment. The expected duration of participation for each subject will not exceed 17 days.

Infants successfully enrolled in this study will take the medication every 12 hours for 5 consecutive days, in total 10 doses. Investigators will regularly score the infants using the Wang bronchiolitis clinical score which is the primary endpoint. Additionally, nasopharyngeal aspirates samples will be collected from the infants for virological testing before the first dose on Days 1 to 5, on Day 6, and on Day 14.

Safety and tolerability assessments in this study will include evaluations of adverse events (AEs)/serious adverse events (SAEs), vital signs and blood oxygen saturation (SpO2) levels, physical examinations, clinical laboratory tests, and electrocardiogram (ECG) findings.

Main Inclusion criteria:

1. Male or female subjects of any ethnicity with an age adjusted for any prematurity of ≥1 month and ≤24 months.
2. Diagnosis of RSV infection by any virological means, including a rapid diagnostic point-of-care testing, within 36 hours preceding initial dosing.
3. The onset of RSV infection symptoms should be ≤ 5 days prior to initial dosing.
4. Subject must weigh ≥ 2.5 kg and ≤ 20 kg at screening and be within the normal range for the subject's age, based on local child growth standards.
5. Subject must have a Wang bronchiolitis clinical score ≥ 5.

Main Exclusion criteria:

1. The subject has taken any restricted medications within 3 days prior to the date of screening or requires any restricted medications during treatment phase (including interferons, ribavirin, or proprietary Chinese medicines with antiviral effects) and has taken any inhaled or systemic glucocorticoids within 24 hours.
2. Subject is known to have co-infection with influenza virus, Mycoplasma, or other respiratory tract pathogens that require targeted clinical treatment .
3. Subject is known to have bacterial pneumonia.
4. Subject with clinical evidence of hepatic decompensation (e.g., liver disease with coagulation abnormalities or encephalopathy).
5. Subject with inborn symptoms of metabolic abnormalities (e.g., mitochondrial diseases, carbohydrate metabolism abnormalities, glycogen accumulation diseases).
6. Subject with chronic or persistent feeding difficulties.
7. The parent or guardian of the subject is an employee of the study investigator or the study facility (such person will be directly involved in the study or any other study administered by the study facility investigator), or a family member of the study investigator or his/her staff.
8. Subject who have participated in clinical trials of other drugs or devices in the 30 days prior to screening.
9. Subject with any other reason that the investigator deems unsuitable for participation in the study.