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Respiratory Syncytial Virus InfectionsPhase 3AIRFLONCT04231968

A Study of AK0529 in Chinese Infants Hospitalized With RSV

A Phase 3 study testing AK0529 in people with Respiratory Syncytial Virus Infections, run by Shanghai Ark Biopharmaceutical Co., Ltd. at 28 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 month to 24 months
Conditions the study is for
Respiratory Syncytial Virus Infections
What is being tested?
AK0529
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
311 participants
Where
28 sitesChina
Study dates
22 Sep 2020to 2 Feb 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 24 months
  • All sexes
  • No healthy volunteers
  • Child

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 the initial dose.
  • The time from the onset caused by RSV infection to the first dose should be ≤ 7 days. Time of onset is defined as the time the first respiratory or systemic signs or symptoms of RSV infection confirmed by the investigator.
  • Body weight ≥ 2.5 kg and ≤ 20 kg at screening.
  • For patients aged <12 months, an occipitofrontal head circumference should be within the normal range for age and gender.
  • Bronchiolitis score ≥ 5.
  • The parent/legal guardian must have provided written informed consent for the patient to participate.

Main Exclusion Criteria:

  • Patients who have used any prohibited medications within 72 hours prior to expected administration and those who have used inhaled or systemic glucocorticosteroids within 24 hours prior to administration.
  • Patients (or mothers of patients younger than 6 months of age) with a known HIV-positive history or patients highly suspected HIV-positive by the investigator.
  • Patients with known co-infection with influenza virus.
  • Patient known to have pneumonia caused by bacterial infection.
  • Patients requiring vasopressors or vasoactive drugs 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 at the time of enrolment, except for the result of RSV infection.
  • Patients at risk for hypercapnia based on their medical history, except for the result of RSV infection.
  • Patient with airway malformations and congenital heart diseases, except for isolated patent ductus arteriosus and/or patent foramen ovale.
  • Renal failure including renal abnormalities likely to be associated with renal insufficiency.
  • Clinical evidence of hepatic decompensation.
  • Symptomatic because of congenital metabolic abnormality.
  • Chronic or persistent feeding difficulties.
  • Known or suspected to have primary immunodeficiency disease.
  • 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 enrolment; in case of any question, discuss such cases with the sponsor's medical monitor.
  • A history of epilepsy or seizures including febrile seizures.
  • History of family history of high allergies or allergies to multiple substances, or presence of severe rash that in the opinion or the investigator renders the patient unsuitable for enrollment.
  • The patient's parent or guardian is an employee of the investigator or the study site with direct involvement in the proposed study or other studies under the direction of that investigator of the study site, 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.

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

China28 sites

  • Beijing Children's Hospital

    Beijing, 100045

  • Peking University Third Hospital

    Beijing, 100191

  • The First Bethune Hospital of Jilin University

    Changchun, 130021

  • Hunan Provincial People's Hospital

    Changsha, 410005

  • West China Women's and Children's Hospital

    Chengdu, 610041

  • Children's Hospital of Chongqing Medical University

    Chongqing, 401122

  • Guangzhou Women and Children's Medical Center

    Guangzhou, 510623

  • The Children's Hospital of Zhejiang University School of Medicine

    Hangzhou, 310030

  • Liaocheng People's Hospital

    Liaocheng, 252000

  • Jiangxi Provincial Children's Hospital

    Nanchang, 330006

  • Children's Hospital of Nanjing Medical University

    Nanjing, 210008

  • Jiangsu Province Hospital

    Nanjing, 210029

  • The First Affiliated Hospital of Guangxi Medical University

    Nanjing, 530021

  • Hainan Third People's Hospital

    Sanya, 572000

  • Children's Hospital of Shanghai

    Shanghai, 200062

  • Shanghai Children's Medical Center

    Shanghai, 200127

  • Shengjing Hospital of China Medical University

    Shengyang, 110004

  • Shenzhen Children's Hospital

    Shenzhen, 518026

  • Children's Hospital of Soochow University

    Suzhou, 215002

  • Tianjin Children's Hospital

    Tianjin, 300074

  • The Second Affiliated Hospital and Yuying Children's Hospital of WMU

    Wenzhou, 325027

  • Wuhan Children's Hospital

    Wuhan, 430016

  • Wuxi Children's Hospital

    Wuxi, 214023

  • The First Affiliated Hospital of Xiamen University

    Xiamen, 361003

  • Xiamen Maternity and Child Healthcare Hospital

    Xiamen, 361100

  • Henan Children's Hospital

    Zhengzhou, 450018

  • The Third Affiliated Hospital of Zhengzhou University

    Zhengzhou, 450052

  • Boai Hospital of Zhongshan

    Zhongshan, 528402

Other trials in China

About this study

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

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.

Being tested
AK0529, Matching placebo of AK0529
Medical subject headings
Respiratory Syncytial Virus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AK0529Drug

    Also called ziresovir

    AK0529 capsule will be orally administered at the twice-daily dosing levels of 10 mg, 20 mg, or 40 mg for five days based on the patient's weight.

  • Matching placebo of AK0529Drug

    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.

Study groups in NCT04231968
Study groupRoleWhat they receive
AK0529ExperimentalParticipants who are randomized to the experimental arm will receive AK0529 twice daily for five days .
Receives: Drug: AK0529
PlaceboPlacebo comparatorParticipants in the control arm will be administered placebo at the matching dosage levels of active medications.
Receives: Drug: Matching placebo of AK0529

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinically significant change from baseline in bronchiolitis score on Day 3

    To demonstrate that AK0529 is superior to placebo in terms of changes from baseline in bronchiolitis signs and symptoms 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. Generally, each score component has a range of values from 0 to 3. A decreasing value of the total score represents a clinical improvement. Unless otherwise noted, the last non-missing measurement/assessment before the first dose of the investigational product is defined as the Baseline measurement. If a measurement/evaluation is performed on the same day of the first dose of the investigational product, these measurements will be considered as Baselines.

    Measured: From Baseline (Pre-dose on Day 1) to Day 3 (48 hours)

Secondary outcomes (39)

  1. Change from baseline in RSV (Respiratory syncytial virus) VL(viral load ) on Day 5

    To evaluate the antiviral effects of AK0529. 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.

    Measured: From Baseline (Pre-dose on Day 1) to Day 5 (96 hours)

  2. Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 2 after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  3. Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 3 after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  4. Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 4 after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  5. Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 5 after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  6. Proportions of subjects with symptom remission on Day 3 after treatment

    Symptom remission is defined as a reduction in clinical bronchiolitis score to 1 or 0 after treatment.

    Measured: Day 3 (48 hours)

  7. Proportions of subjects with symptom remission at other visits after treatment

    Symptom remission is defined as a reduction in clinical bronchiolitis score to 1 or 0 after treatment.

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)

  8. Proportions of subjects with ≥ 75% reduction from baseline in bronchiolitis score on Day 3 after treatment

    Measured: Day 3 (48 hours)

  9. Proportions of subjects with ≥ 75% reduction from baseline in bronchiolitis score at other visits after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)

  10. Proportions of subjects with disease remission on Day 3 after treatment

    Disease remission is defined as a reduction in bronchiolitis score to 1 or 0 after treatment, without non-invasive positive pressure ventilation or assisted mechanical ventilation or supplemental oxygen therapy.

    Measured: From Baseline (Pre-dose on Day 1) to Day 3 (48 hours)

  11. Proportions of subjects with disease remission at other visits after treatment.

    Disease remission is defined as a reduction in bronchiolitis score to 1 or 0 after treatment, without non-invasive positive pressure ventilation or assisted mechanical ventilation or supplemental oxygen therapy.

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)

  12. Time from the first dose to symptom remission

    Symptom remission is defined as a reduction in clinical bronchiolitis score to 1 or 0 after treatment.

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  13. Time from the first dose to a zero general symptom score for subjects with general symptoms sub-scores equal to 3 at baseline

    The General Symptom score is part of the Bronchiolitis Score and has only two scores, 3 and 0. A normal patient is a 0, and the presence of irritable, lethargic, poor feeding is rated as 3.

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  14. Time from the first dose to a ≥ 75% reduction in bronchiolitis score

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  15. Time from the first dose to disease remission

    Disease remission is defined as a reduction in bronchiolitis score to 1 or 0 after treatment, without non-invasive positive pressure ventilation or assisted mechanical ventilation or supplemental oxygen therapy.

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  16. Change in bronchiolitis score and percentage change from baseline at each visit after treatment (except Day 3)

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 3)

  17. Change from baseline in bronchiolitis sub-score at each visit after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  18. Proportions of subjects with the change in bronchiolitis sub-score values at each visit after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  19. Proportions of subjects achieving a ≥ 50% reduction from baseline in bronchiolitis score after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  20. Proportions of subjects achieving a ≥ 90% reduction from baseline in bronchiolitis score after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  21. Respiratory sequelae of subjects from the end of the safety observation period to Month 6

    The assessment of respiratory sequelae involves evaluating the frequency, duration, and treatment related to wheezing recurrences and the presence of confirmed asthma.

    Measured: From Day 14 to Month 6

  22. Respiratory sequelae of subjects from the end of the safety observation period to the end of the second year

    The assessment of respiratory sequelae involves evaluating the frequency, duration, and treatment related to wheezing recurrences and the presence of confirmed asthma.

    Measured: From Day 14 to end of Year 2

  23. Analysis of subjects admitted to intensive care unit (ICU) for diseases related to RSV infection

    Analyzed by the number of admissions, duration of admission, and the duration from the first dose to the end of ICU.

    Measured: From Baseline to the end of ICU

  24. Analysis of subjects receiving non-invasive positive pressure ventilation or assisted mechanical ventilation

    Analyzed by the number of subjects receiving non-invasive positive pressure ventilation or assisted mechanical ventilation, duration of such ventilation, and the time from the first dose to the end of assisted ventilation.

    Measured: From Baseline to Day 14

  25. Analysis of subjects receiving supplemental oxygen therapy

    Analyzed by the number of subjects receiving supplemental oxygen therapy, duration of such therapy, and the time from the first dose to supplemental oxygen therapy.

    Measured: From first treatment to Day 14

  26. Proportions of subjects with RSV VL below the lower limit of quantification (LLOQ) on Day 5 after treatment

    Measured: Day 5 (96hours)

  27. Proportions of subjects with RSV VL below the LLOQ at other visits

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 5)

  28. Change from baseline in RSV VL at each visit except Day 5 after treatment

    Measured: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 5)

  29. Area under the curve of RSV VL from baseline to the last measurement

    Measured: From Baseline (Pre-dose on Day 1) to Day 14

  30. Analysis of clinical efficacy of AK0529 in different subgroups

    Analyzed in different subgroups categorized by, at a minimum, months of age, severity of baseline Bronchiolitis Score, time from onset of RSV infection to first dose, RSV viral subtypes, baseline RSV VL classifications, and doses.

    Measured: From Baseline to Day 14

  31. Proportion of subjects with adverse events (AEs) occurring during the study

    To evaluate the safety and tolerability of AK0529.

    Measured: From Baseline to Day 14

  32. Proportion of subjects with serious adverse events (SAEs) occurring during the study

    To evaluate the safety and tolerability of AK0529.

    Measured: From Baseline to Day 14

  33. Proportion of subjects who withdraw from the study due to AEs during the study

    To evaluate the safety and tolerability of AK0529.

    Measured: From Baseline to Day 14

  34. Maximum plasma concentration of AK0529 (Cmax)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

  35. Plasma drug trough concentration of AK0529 (Ctrough)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

  36. Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

  37. Apparent total body clearance (CL/F)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

  38. Apparent volume of distribution (Vz/F)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

  39. Elimination half-life (t½)

    PK parameters of AK0529 and its metabolites using population pharmacokinetic (POP-PK) and other appropriate methods.

    Measured: At 3 and 24 hours after the first dose and on Day 6 (120 hours)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start22 Sep 2020
  3. Primary completion21 Jan 2022
  4. Study completion2 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
311 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04231968
Sponsor's protocol ID
AK0529-2003
Acronym
AIRFLO
Status last verified
Feb 2024
First submitted
12 Jan 2020
Last updated
13 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang H, Zhao W, Zhang X, Zhang L, Guo R, Huang H, Lin L, Liu F, Chen H, Shen F, Wu J, Huang X, Zhu X, Li F, Zou G, Chien J, Humphries M, Lu Q, Wu JZ, Zhao S, Liu H, Ni X; AIRFLO Study Group. Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up. Lancet Child Adolesc Health. 2025 May;9(5):325-336. doi: 10.1016/S2352-4642(25)00067-7.

    PubMed 40246359

  • Zhao S, Shang Y, Yin Y, Zou Y, Xu Y, Zhong L, Zhang H, Zhang H, Zhao D, Shen T, Huang D, Chen Q, Yang Q, Yang Y, Dong X, Li L, Chen Z, Liu E, Deng L, Jiang W, Cheng H, Nong G, Wang X, Chen Y, Ding R, Zhou W, Zheng Y, Shen Z, Lu X, Hao C, Zhu X, Jia T, Wu Y, Zou G, Rito K, Wu JZ, Liu H, Ni X; AIRFLO Study Group. Ziresovir in Hospitalized Infants with Respiratory Syncytial Virus Infection. N Engl J Med. 2024 Sep 26;391(12):1096-1107. doi: 10.1056/NEJMoa2313551.

    PubMed 39321361

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing AK0529 in people with Respiratory Syncytial Virus Infections, run by Shanghai Ark Biopharmaceutical Co., Ltd. at 28 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinically significant change from baseline in bronchiolitis score on Day 3 (time frame: From Baseline (Pre-dose on Day 1) to Day 3 (48 hours)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04231968, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.

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