A Study of AK0529 in Chinese Infants Hospitalized With RSV (AirFLO)
Primary Purpose
Respiratory Syncytial Virus Infections
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
AK0529
Matching placebo of AK0529
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Syncytial Virus Infections
Eligibility Criteria
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.
Sites / Locations
- Beijing Children's Hospital
- Peking University Third Hospital
- The First Bethune Hospital of Jilin University
- Hunan Provincial People's Hospital
- West China Women's and Children's Hospital
- Children's Hospital of Chongqing Medical University
- Guangzhou Women and Children's Medical Center
- The Children's Hospital of Zhejiang University School of Medicine
- Liaocheng People's Hospital
- Jiangxi Provincial Children's Hospital
- Children's Hospital of Nanjing Medical University
- Jiangsu Province Hospital
- The First Affiliated Hospital of Guangxi Medical University
- Hainan Third People's Hospital
- Children's Hospital of Shanghai
- Shanghai Children's Medical Center
- Shengjing Hospital of China Medical University
- Shenzhen Children's Hospital
- Children's Hospital of Soochow University
- Tianjin Children's Hospital
- The Second Affiliated Hospital and Yuying Children's Hospital of WMU
- Wuhan Children's Hospital
- Wuxi Children's Hospital
- The First Affiliated Hospital of Xiamen University
- Xiamen Maternity and Child Healthcare Hospital
- Henan Children's Hospital
- The Third Affiliated Hospital of Zhengzhou University
- Boai Hospital of Zhongshan
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AK0529
Placebo
Arm Description
Participants who are randomized to the experimental arm will receive AK0529 twice daily for five days .
Participants in the control arm will be administered placebo at the matching dosage levels of active medications.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Proportions of subjects with bronchiolitis score decreased ≥2
The proportion of subjects whose bronchiolitis score decreased by ≥2 after treatment compared with the baseline.
Proportions of subjects with bronchiolitis score decreased ≥3
The proportion of subjects whose bronchiolitis score decreased by ≥3 after treatment compared with the baseline.
Proportions of subjects with bronchiolitis score decreased ≥4
The proportion of subjects whose bronchiolitis score decreased by ≥4 after treatment compared with the baseline.
Proportions of subjects with bronchiolitis score decreased ≥5
The proportion of subjects whose bronchiolitis score decreased by ≥5 after treatment compared with the baseline.
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.
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.
Proportions of subjects achieving ≥75% bronchiolitis score decrease
The proportion of subjects whose bronchiolitis score decreased by ≥75% after treatment compared with baseline.
Proportions of subjects achieving ≥50% bronchiolitis score decrease
The proportion of subjects whose bronchiolitis score decreased by ≥50% after treatment compared with baseline.
Proportions of subjects achieving ≥90% bronchiolitis score decrease
The proportion of subjects whose bronchiolitis score decreased by ≥90% after treatment compared with baseline.
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.
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.
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.
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.
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.
Differences of frequency of Intensive Care Unit (ICU) admission
The differences of frequency of ICU admission between AK0529 and placebo arms.
Differences of length of ICU stay
The differences of length of ICU stay between AK0529 and placebo arms.
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.
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.
Full Information
NCT ID
NCT04231968
First Posted
January 12, 2020
Last Updated
March 31, 2022
Sponsor
Ark Biosciences Inc.
Collaborators
Shanghai Ark Biopharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04231968
Brief Title
A Study of AK0529 in Chinese Infants Hospitalized With RSV
Acronym
AirFLO
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
September 23, 2020 (Actual)
Primary Completion Date
January 23, 2022 (Actual)
Study Completion Date
February 1, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ark Biosciences Inc.
Collaborators
Shanghai Ark Biopharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
311 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AK0529
Arm Type
Experimental
Arm Description
Participants who are randomized to the experimental arm will receive AK0529 twice daily for five days .
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in the control arm will be administered placebo at the matching dosage levels of active medications.
Intervention Type
Drug
Intervention Name(s)
AK0529
Other Intervention Name(s)
ziresovir
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Matching placebo of AK0529
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes of bronchiolitis score
Description
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.
Time Frame
Baseline and Day 3
Secondary Outcome Measure Information:
Title
Changes of bronchiolitis score
Description
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.
Time Frame
baseline, Day 1, Day 2, Day 4, Day 5, Day 6, and Day 14
Title
Changes of viral load
Description
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.
Time Frame
From baseline through study completion, up to to Day 14
Title
Changes of area under curve of viral load
Description
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.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects with viral load below LLOQ
Description
The proportion of subjects whose viral load values are below LLOQ (lower limit of quantitation) after treatment.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects with bronchiolitis score decreased ≥2
Description
The proportion of subjects whose bronchiolitis score decreased by ≥2 after treatment compared with the baseline.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects with bronchiolitis score decreased ≥3
Description
The proportion of subjects whose bronchiolitis score decreased by ≥3 after treatment compared with the baseline.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects with bronchiolitis score decreased ≥4
Description
The proportion of subjects whose bronchiolitis score decreased by ≥4 after treatment compared with the baseline.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects with bronchiolitis score decreased ≥5
Description
The proportion of subjects whose bronchiolitis score decreased by ≥5 after treatment compared with the baseline.
Time Frame
From baseline through study completion, up to to Day 14
Title
Proportions of subjects achieving symptom remission
Description
The proportion of subjects who achieved symptom remission after treatment compared with the baseline. Symptom remission was defined as bronchiolitis score ≤1.
Time Frame
Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14
Title
Proportions of subjects achieving disease remission
Description
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.
Time Frame
Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14
Title
Proportions of subjects achieving ≥75% bronchiolitis score decrease
Description
The proportion of subjects whose bronchiolitis score decreased by ≥75% after treatment compared with baseline.
Time Frame
Baseline, Day 3, Day 4, Day 5, Day 6, and Day 14
Title
Proportions of subjects achieving ≥50% bronchiolitis score decrease
Description
The proportion of subjects whose bronchiolitis score decreased by ≥50% after treatment compared with baseline.
Time Frame
Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, and Day 14
Title
Proportions of subjects achieving ≥90% bronchiolitis score decrease
Description
The proportion of subjects whose bronchiolitis score decreased by ≥90% after treatment compared with baseline.
Time Frame
Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, and Day 14
Title
Time from first treatment to symptom remission
Description
The time difference from the first treatment to the time subjects achieved symptom remission between the AK0529 and placebo arms.
Time Frame
From first treatment through study completion, up to to Day 14
Title
Time from first treatment to disease remission
Description
The time difference from the first treatment to the time subjects achieved disease remission between the AK0529 and placebo arms.
Time Frame
From first treatment through study completion, up to to Day 14
Title
Time from first treatment to general condition scoring zero
Description
The time difference from the first treatment to the time general condition score dropped to zero between the AK0529 and placebo arms.
Time Frame
From first treatment through study completion, up to to Day 14
Title
Time from first treatment to ≥75% decrease in bronchiolitis score
Description
The time difference from the first treatment to the time subjects achieved ≥75% decrease in bronchiolitis score between the AK0529 and placebo arms.
Time Frame
From first treatment through study completion, up to to Day 14
Title
Time from first treatment to assisting ventilation withdrwal
Description
The time difference from the first treatment to the end of assisting ventilation therapy in subjects between the AK0529 and placebo arms.
Time Frame
From first treatment through study completion, up to to Day 14
Title
Differences of frequency of Intensive Care Unit (ICU) admission
Description
The differences of frequency of ICU admission between AK0529 and placebo arms.
Time Frame
From baseline through study completion, up to to Day 14
Title
Differences of length of ICU stay
Description
The differences of length of ICU stay between AK0529 and placebo arms.
Time Frame
From baseline through study completion, up to to Day 14
Title
Incidence of adverse events (AE)
Description
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.
Time Frame
From baseline through study completion, up to to Day 14
Title
Subject withdrawals due to TEAE
Description
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.
Time Frame
From baseline through study completion, up to to Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jimmy Gu
Organizational Affiliation
info@arkbiosciences.com
Official's Role
Study Director
Facility Information:
Facility Name
Beijing Children's Hospital
City
Beijing
ZIP/Postal Code
100045
Country
China
Facility Name
Peking University Third Hospital
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
The First Bethune Hospital of Jilin University
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
Hunan Provincial People's Hospital
City
Changsha
ZIP/Postal Code
410005
Country
China
Facility Name
West China Women's and Children's Hospital
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
ZIP/Postal Code
401122
Country
China
Facility Name
Guangzhou Women and Children's Medical Center
City
Guangzhou
ZIP/Postal Code
510623
Country
China
Facility Name
The Children's Hospital of Zhejiang University School of Medicine
City
Hangzhou
ZIP/Postal Code
310030
Country
China
Facility Name
Liaocheng People's Hospital
City
Liaocheng
ZIP/Postal Code
252000
Country
China
Facility Name
Jiangxi Provincial Children's Hospital
City
Nanchang
ZIP/Postal Code
330006
Country
China
Facility Name
Children's Hospital of Nanjing Medical University
City
Nanjing
ZIP/Postal Code
210008
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
ZIP/Postal Code
210029
Country
China
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanjing
ZIP/Postal Code
530021
Country
China
Facility Name
Hainan Third People's Hospital
City
Sanya
ZIP/Postal Code
572000
Country
China
Facility Name
Children's Hospital of Shanghai
City
Shanghai
ZIP/Postal Code
200062
Country
China
Facility Name
Shanghai Children's Medical Center
City
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Shengjing Hospital of China Medical University
City
Shengyang
ZIP/Postal Code
110004
Country
China
Facility Name
Shenzhen Children's Hospital
City
Shenzhen
ZIP/Postal Code
518026
Country
China
Facility Name
Children's Hospital of Soochow University
City
Suzhou
ZIP/Postal Code
215002
Country
China
Facility Name
Tianjin Children's Hospital
City
Tianjin
ZIP/Postal Code
300074
Country
China
Facility Name
The Second Affiliated Hospital and Yuying Children's Hospital of WMU
City
Wenzhou
ZIP/Postal Code
325027
Country
China
Facility Name
Wuhan Children's Hospital
City
Wuhan
ZIP/Postal Code
430016
Country
China
Facility Name
Wuxi Children's Hospital
City
Wuxi
ZIP/Postal Code
214023
Country
China
Facility Name
The First Affiliated Hospital of Xiamen University
City
Xiamen
ZIP/Postal Code
361003
Country
China
Facility Name
Xiamen Maternity and Child Healthcare Hospital
City
Xiamen
ZIP/Postal Code
361100
Country
China
Facility Name
Henan Children's Hospital
City
Zhengzhou
ZIP/Postal Code
450018
Country
China
Facility Name
The Third Affiliated Hospital of Zhengzhou University
City
Zhengzhou
ZIP/Postal Code
450052
Country
China
Facility Name
Boai Hospital of Zhongshan
City
Zhongshan
ZIP/Postal Code
528402
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of AK0529 in Chinese Infants Hospitalized With RSV
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