A Study of AK0529 in Chinese Infants Hospitalized With RSV

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multicenter, phase III study to be conducted in infants hospitalized with RSV infection in China. The main objectives of this study are to investigate the efficacy and safety of AK0529 in Chinese infants.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 2-part Study of Orally Administered AK0529 to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Antiviral Effect of Multiple Doses in Hospitalized Infants With Respiratory Syncytial Virus Infection

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: AK0529
* Drug: Matching placebo of AK0529


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male or female patients of any ethnicity with an age-adjusted for any prematurity of ≥1 month and ≤24 months. Diagnosis of RSV infection by any virological means within 36 hours preceding initial dosing. Onset of RSV infection symptoms should be ≤ 7 days. Patient must weigh ≥ 2.5 kg and ≤ 20 kg at screening. For patients aged <12 months, and occipitofrontal head circumference within the normal range for age and gender. Patient must have a bronchiolitis score ≥ 5. The parent/legal guardian must have provided written informed consent for the patient to participate. Main Exclusion Criteria: The patient has taken any restricted medications within 72 hours prior to the date of screening or requires any restricted medications during the treatment phase. Patient is known to be HIV-positive (or the mother, if the potential patient is a child aged <6 months). Patient is known to be infected by Influenza. Patient is known to have bacterial pneumonia. Requires vasopressors or inotropic support at the time of enrollment. Concurrent gastrointestinal conditions that could seriously, in the opinion of the investigator, prejudice absorption of the Investigational Medicinal Product. Bronchopulmonary dysplasia requiring assisted ventilation, except for the result of RSV infection. Patient is at risk for hypercapnia. Patient with airway malformations and congenital heart diseases, except for isolated patent ductus arteriosus and/or patent foramen ovale. Renal failure including renal anomalies likely to be associated with renal insufficiency. Clinical evidence of hepatic decompensation. Symptomatic because of inborn errors of metabolism. Chronic or persistent feeding difficulties. Suspected or known to have congenital acquired immunodeficiency. Any active or uncontrolled respiratory, cardiac, hepatic, central nervous system, or renal disease unrelated to RSV infection at baseline or any other medical condition that in the opinion of the investigator renders the patient unsuitable for enrollment. A history of epilepsy or seizures. A history of high allergies. The patient's parent or legally acceptable representative is an employee of the investigator or the study center with direct involvement in the proposed study or other studies under the direction of that investigator of the study center, or any family members of the employees or the investigator. Participation in an investigational drug or device study within 30 days prior to the date of screening. Failure to satisfy the investigator of fitness to participate for any other reason.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK0529<br>Participants who are randomized to the experimental arm will receive AK0529 twice daily for five days . | Drug: AK0529<br>* AK0529 capsule will be orally administered at the twice-daily dosing levels of 10 mg, 20 mg, or 40 mg for five days according to the weight of patients.<br>* Other names: ziresovir;|
| Placebo Comparator: Placebo<br>Participants in the control arm will be administered placebo at the matching dosage levels of active medications. | Drug: Matching placebo of AK0529<br>* The placebo capsule was made with the same smell and appearance as AK0529 but without the active ingredients and will be orally administered per the same treatment schedule as those in the experimental arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of bronchiolitis score | The differences of change in the bronchiolitis score are to be evaluated between the AK0529 and placebo arms after treatment. The total score is reported with a range from 0 to 12. The minimum and maximum values of 0 and 3 separately are defined for each scoring item. A decreasing value of the total score represents a clinical improvement. Subscales are not applicable in this scoring system. | Baseline and Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of bronchiolitis score | The differences in changes in the bronchiolitis score are to be evaluated between the AK0529 and placebo arms after treatment. The total score is reported with a range from 0 to 12. The minimum and maximum values of 0 and 3 separately are defined for each scoring item. A decreasing value of the total score represents a clinical improvement. Subscales are not applicable in this scoring system. | baseline, Day 1, Day 2, Day 4, Day 5, Day 6, and Day 14 | 
| Changes of viral load | The antiviral effects in infants hospitalized with RSV are to be determined by measuring the differences in viral load determined by RT-PCR between the AK0529 and placebo arms after treatment. | From baseline through study completion, up to to Day 14 | 
| Changes of area under curve of viral load | The antiviral effects are to be determined by measuring the differences in area under curve (AUC) of viral load between the AK0529 and placebo arms after treatment. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects with viral load below LLOQ | The proportion of subjects whose viral load values are below LLOQ (lower limit of quantitation) after treatment. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects with bronchiolitis score decreased ≥2 | The proportion of subjects whose bronchiolitis score decreased by ≥2 after treatment compared with the baseline. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects with bronchiolitis score decreased ≥3 | The proportion of subjects whose bronchiolitis score decreased by ≥3 after treatment compared with the baseline. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects with bronchiolitis score decreased ≥4 | The proportion of subjects whose bronchiolitis score decreased by ≥4 after treatment compared with the baseline. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects with bronchiolitis score decreased ≥5 | The proportion of subjects whose bronchiolitis score decreased by ≥5 after treatment compared with the baseline. | From baseline through study completion, up to to Day 14 | 
| Proportions of subjects achieving symptom remission | The proportion of subjects who achieved symptom remission after treatment compared with the baseline. Symptom remission was defined as bronchiolitis score ≤1. | Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14 | 
| Proportions of subjects achieving disease remission | The proportion of subjects who achieved disease remission after treatment compared with the baseline. Disease remission was defined as bronchiolitis score ≤1 and with no assisted ventilation. | Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14 | 
| Proportions of subjects achieving ≥75% bronchiolitis score decrease | The proportion of subjects whose bronchiolitis score decreased by ≥75% after treatment compared with baseline. | Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14 | 
| Proportions of subjects achieving ≥50% bronchiolitis score decrease | The proportion of subjects whose bronchiolitis score decreased by ≥50% after treatment compared with baseline. | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, and Day 14 | 
| Proportions of subjects achieving ≥90% bronchiolitis score decrease | The proportion of subjects whose bronchiolitis score decreased by ≥90% after treatment compared with baseline. | Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, and Day 14 | 
| Time from first treatment to symptom remission | The time difference from the first treatment to the time subjects achieved symptom remission between the AK0529 and placebo arms. | From first treatment through study completion, up to to Day 14 | 
| Time from first treatment to disease remission | The time difference from the first treatment to the time subjects achieved disease remission between the AK0529 and placebo arms. | From first treatment through study completion, up to to Day 14 | 
| Time from first treatment to general condition scoring zero | The time difference from the first treatment to the time general condition score dropped to zero between the AK0529 and placebo arms. | From first treatment through study completion, up to to Day 14 | 
| Time from first treatment to ≥75% decrease in bronchiolitis score | The time difference from the first treatment to the time subjects achieved ≥75% decrease in bronchiolitis score between the AK0529 and placebo arms. | From first treatment through study completion, up to to Day 14 | 
| Time from first treatment to assisting ventilation withdrwal | The time difference from the first treatment to the end of assisting ventilation therapy in subjects between the AK0529 and placebo arms. | From first treatment through study completion, up to to Day 14 | 
| Differences of frequency of Intensive Care Unit (ICU) admission | The differences of frequency of ICU admission between AK0529 and placebo arms. | From baseline through study completion, up to to Day 14 | 
| Differences of length of ICU stay | The differences of length of ICU stay between AK0529 and placebo arms. | From baseline through study completion, up to to Day 14 | 
| Incidence of adverse events (AE) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | From baseline through study completion, up to to Day 14 | 
| Subject withdrawals due to TEAE | A treatment-emergent adverse event (TEAE) is an AE that first appears during treatment, which was absent before or which worsens relative to the pre-treatment state. | From baseline through study completion, up to to Day 14 |