A Study of AK0529 in Chinese Infants Hospitalized With RSV

Phase 3CompletedNCT04231968

Shanghai Ark Biopharmaceutical Co., Ltd.311 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

311

Conditions

Respiratory Syncytial Virus Infections

Interventions

AK0529DRUG

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.

Eligibility

Sex: ALLMin age: 1 MonthMax age: 24 Months

Medical Language ↔ Plain English

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.

Locations (28)

Outcomes

Primary Outcomes

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.

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

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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

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

Data from ClinicalTrials.gov

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Beijing Children's Hospital

Beijing, China

Peking University Third Hospital

Beijing, China

The First Bethune Hospital of Jilin University

Changchun, China

Hunan Provincial People's Hospital

Changsha, China

West China Women's and Children's Hospital

Chengdu, China

Children's Hospital of Chongqing Medical University

Chongqing, China

Guangzhou Women and Children's Medical Center

Guangzhou, China

The Children's Hospital of Zhejiang University School of Medicine

Hangzhou, China

Liaocheng People's Hospital

Liaocheng, China

Jiangxi Provincial Children's Hospital

Nanchang, China

...and 18 more locations

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

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

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.

Time frame: Day 3 (48 hours)

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.

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

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

Time frame: Day 3 (48 hours)

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

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

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.

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

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

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

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.

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

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.

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

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

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

Time from the first dose to disease remission

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

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

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

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

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

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

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

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

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

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

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

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.

Time frame: From Day 14 to Month 6

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.

Time frame: From Day 14 to end of Year 2

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.

Time frame: From Baseline to the end of ICU

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.

Time frame: From Baseline to Day 14

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.

Time frame: From first treatment to Day 14

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

Time frame: Day 5 (96hours)

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

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

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

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

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

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

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.

Time frame: From Baseline to Day 14

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

To evaluate the safety and tolerability of AK0529.

Time frame: From Baseline to Day 14

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

To evaluate the safety and tolerability of AK0529.

Time frame: From Baseline to Day 14

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

To evaluate the safety and tolerability of AK0529.

Time frame: From Baseline to Day 14

Maximum plasma concentration of AK0529 (Cmax)

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

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

Plasma drug trough concentration of AK0529 (Ctrough)

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

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

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.

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

Apparent total body clearance (CL/F)

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

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

Apparent volume of distribution (Vz/F)

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

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

Elimination half-life (t½)

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

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