A Study of AK0529 in Chinese Infants Hospitalized With RSV

NCT04231968 | Completed Phase 3 DMC

• 1 other identifier: AK0529-2003
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 28

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.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (39)

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

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

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

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

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

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

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

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

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

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

Other Outcomes (12)

• RSV VL and primary and selected secondary efficacy measurements

  From Baseline to Day 14

• Selective primary efficacy, secondary efficacy, and safety measures for the pharmacokinetic-pharmacodynamic (PK-PD) analysis

  From Baseline to Day 6

• Proportions of subjects with mutations at 20 reported sites associated with RSV fusion inhibitor-resistant mutations in RSV F genesequences after treatment compared to baseline

  From Baseline to Day 14

Study Arms (2)

AK0529

EXPERIMENTAL

Participants who are randomized to the experimental arm will receive AK0529 twice daily for five days .

Drug: AK0529

Placebo

PLACEBO COMPARATOR

Participants in the control arm will be administered placebo at the matching dosage levels of active medications.

Drug: Matching placebo of AK0529

Interventions

AK0529 DRUG

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.

Also known as: ziresovir

AK0529

Matching placebo of AK0529 DRUG

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.

Placebo

Eligibility Criteria

• Age: 1 Month - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Ark Biopharmaceutical Co., Ltd.: lead

Study Sites (28)

Beijing Children's Hospital

Beijing, 100045, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

The First Bethune Hospital of Jilin University

Changchun, 130021, China

Location

Hunan Provincial People's Hospital

Changsha, 410005, China

Location

West China Women's and Children's Hospital

Chengdu, 610041, China

Location

Children's Hospital of Chongqing Medical University

Chongqing, 401122, China

Location

Guangzhou Women and Children's Medical Center

Guangzhou, 510623, China

Location

The Children's Hospital of Zhejiang University School of Medicine

Hangzhou, 310030, China

Location

Liaocheng People's Hospital

Liaocheng, 252000, China

Location

Jiangxi Provincial Children's Hospital

Nanchang, 330006, China

Location

Children's Hospital of Nanjing Medical University

Nanjing, 210008, China

Location

Jiangsu Province Hospital

Nanjing, 210029, China

Location

The First Affiliated Hospital of Guangxi Medical University

Nanjing, 530021, China

Location

Hainan Third People's Hospital

Sanya, 572000, China

Location

Children's Hospital of Shanghai

Shanghai, 200062, China

Location

Shanghai Children's Medical Center

Shanghai, 200127, China

Location

Shengjing Hospital of China Medical University

Shengyang, 110004, China

Location

Shenzhen Children's Hospital

Shenzhen, 518026, China

Location

Children's Hospital of Soochow University

Suzhou, 215002, China

Location

Tianjin Children's Hospital

Tianjin, 300074, China

Location

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

Wenzhou, 325027, China

Location

Wuhan Children's Hospital

Wuhan, 430016, China

Location

Wuxi Children's Hospital

Wuxi, 214023, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Xiamen Maternity and Child Healthcare Hospital

Xiamen, 361100, China

Location

Henan Children's Hospital

Zhengzhou, 450018, China

Location

The Third Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China

Location

Boai Hospital of Zhongshan

Zhongshan, 528402, China

Location

Related Publications (2)

• 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.

  PMID: 40246359 DERIVED

• 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.

  PMID: 39321361 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

ziresovir

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Yu Chen, MD

  yu.chen@arkbiosciences.com

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2020
• First Posted: January 18, 2020
• Study Start: September 22, 2020
• Primary Completion: January 21, 2022
• Study Completion: February 2, 2022
• Last Updated: February 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (28)