Clinical trial NCT04231968: A Study of AK0529 in Chinese Infants Hospitalized With RSV
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-01-18
Enrollment: 311
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Clinically significant change from baseline in bronchiolitis score on Day 3
timeFrame: From Baseline (Pre-dose on Day 1) to Day 3 (48 hours)
Secondary outcomes:
measure: Change from baseline in RSV (Respiratory syncytial virus) VL(viral load ) on Day 5
timeFrame: From Baseline (Pre-dose on Day 1) to Day 5 (96 hours)
measure: Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 2 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 3 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 4 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects with a reduction from baseline in clinical bronchiolitis score ≥ 5 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects with symptom remission on Day 3 after treatment
timeFrame: Day 3 (48 hours)
measure: Proportions of subjects with symptom remission at other visits after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)
measure: Proportions of subjects with ≥ 75% reduction from baseline in bronchiolitis score on Day 3 after treatment
timeFrame: Day 3 (48 hours)
measure: Proportions of subjects with ≥ 75% reduction from baseline in bronchiolitis score at other visits after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)
measure: Proportions of subjects with disease remission on Day 3 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 3 (48 hours)
measure: Proportions of subjects with disease remission at other visits after treatment.
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except for Day 3)
measure: Time from the first dose to symptom remission
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Time from the first dose to a zero general symptom score for subjects with general symptoms sub-scores equal to 3 at baseline
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Time from the first dose to a ≥ 75% reduction in bronchiolitis score
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Time from the first dose to disease remission
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Change in bronchiolitis score and percentage change from baseline at each visit after treatment (except Day 3)
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 3)
measure: Change from baseline in bronchiolitis sub-score at each visit after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects with the change in bronchiolitis sub-score values at each visit after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects achieving a ≥ 50% reduction from baseline in bronchiolitis score after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Proportions of subjects achieving a ≥ 90% reduction from baseline in bronchiolitis score after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Respiratory sequelae of subjects from the end of the safety observation period to Month 6
timeFrame: From Day 14 to Month 6
measure: Respiratory sequelae of subjects from the end of the safety observation period to the end of the second year
timeFrame: From Day 14 to end of Year 2
measure: Analysis of subjects admitted to intensive care unit (ICU) for diseases related to RSV infection
timeFrame: From Baseline to the end of ICU
measure: Analysis of subjects receiving non-invasive positive pressure ventilation or assisted mechanical ventilation
timeFrame: From Baseline to Day 14
measure: Analysis of subjects receiving supplemental oxygen therapy
timeFrame: From first treatment to Day 14
measure: Proportions of subjects with RSV VL below the lower limit of quantification (LLOQ) on Day 5 after treatment
timeFrame: Day 5 (96hours)
measure: Proportions of subjects with RSV VL below the LLOQ at other visits
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 5)
measure: Change from baseline in RSV VL at each visit except Day 5 after treatment
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14 (except Day 5)
measure: Area under the curve of RSV VL from baseline to the last measurement
timeFrame: From Baseline (Pre-dose on Day 1) to Day 14
measure: Analysis of clinical efficacy of AK0529 in different subgroups
timeFrame: From Baseline to Day 14
measure: Proportion of subjects with adverse events (AEs) occurring during the study
timeFrame: From Baseline to Day 14
measure: Proportion of subjects with serious adverse events (SAEs) occurring during the study
timeFrame: From Baseline to Day 14
measure: Proportion of subjects who withdraw from the study due to AEs during the study
timeFrame: From Baseline to Day 14
measure: Maximum plasma concentration of AK0529 (Cmax)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
measure: Plasma drug trough concentration of AK0529 (Ctrough)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
measure: Apparent total body clearance (CL/F)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
measure: Apparent volume of distribution (Vz/F)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
measure: Elimination half-life (t½)
timeFrame: At 3 and 24 hours after the first dose and on Day 6 (120 hours)
Other outcomes:
measure: RSV VL and primary and selected secondary efficacy measurements
timeFrame: From Baseline to Day 14
measure: Selective primary efficacy, secondary efficacy, and safety measures for the pharmacokinetic-pharmacodynamic (PK-PD) analysis
timeFrame: From Baseline to Day 6
measure: 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
timeFrame: From Baseline to Day 14
measure: Proportions of subjects detected with other respiratory disease-associated viruses at baseline
timeFrame: Baseline (Pre-dose on Day 1)
measure: Changes in respiratory rate during the study
timeFrame: From Baseline through Day 6
measure: Changes in heart rate during the study
timeFrame: From Baseline through Day 6
measure: Changes in body temperature during the study
timeFrame: From Baseline through Day 6
measure: Changes in systolic blood pressure during the study
timeFrame: From Baseline through Day 6
measure: Changes in diastolic blood pressure during the study
timeFrame: From Baseline through Day 6
measure: Changes in SpO2 during the study
timeFrame: From Baseline through Day 6
measure: Duration of hospitalization of subjects with RSV infection
timeFrame: From the day of patient admission to the day of patient discharge
measure: Time from first dose to discharge of subjects with RSV infection
timeFrame: From Baseline (Day 1) to the day of patient discharge
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
city: Chengdu
country: China
facility: West China Women's and Children's Hospital
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
city: Guangzhou
country: China
facility: Guangzhou Women and Children's Medical Center
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
city: Nanchang
country: China
facility: Jiangxi Provincial Children's Hospital
city: Nanjing
country: China
facility: Children's Hospital of Nanjing Medical University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
city: Sanya
country: China
facility: Hainan Third People's Hospital
city: Shanghai
country: China
facility: Children's Hospital of Shanghai
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
city: Suzhou
country: China
facility: Children's Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Children's Hospital
city: Wenzhou
country: China
facility: The Second Affiliated Hospital and Yuying Children's Hospital of WMU
city: Wuhan
country: China
facility: Wuhan Children's Hospital
city: Wuxi
country: China
facility: Wuxi Children's Hospital
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Xiamen Maternity and Child Healthcare Hospital
city: Zhengzhou
country: China
facility: Henan Children's Hospital
city: Zhengzhou
country: China
facility: The Third Affiliated Hospital of Zhengzhou University
city: Zhongshan
country: China
facility: Boai Hospital of Zhongshan
Study officials:
affiliation: yu.chen@arkbiosciences.com
name: Yu Chen, MD
role: STUDY_DIRECTOR
References: