A Randomized, Double-blind, Placebo-controlled Phase II/III Clinical Trial to Evaluate the Safety and Efficacy of Deuremidevir Hydrobromide for Suspension in Hospitalized Infants Infected With Respiratory Syncytial Virus.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 22
- 主要终点
- Changes of area under curve of viral load
研究概览
简要总结
To evaluate the safety, efficacy, pharmacokinetic (PK) characteristics and antiviral activity of different doses of Deuterium Hydrobromide for suspension in the treatment of respiratory syncytial virus infection in infants.
详细描述
This trial is a randomized, double-blind, placebo-controlled, dose-ascending trial, and the subjects are infants infected with RSV from 1 to 24 months.
It is estimated that 60 subjects will be included and divided into low-dose group (15 mg/kg，BID), middle-dose group (20 mg/kg,BID) and high-dose group (20 mg/kg,TID), with 20 cases in each group, and they will be randomly assigned to the experimental drug group and the placebo group according to the ratio of 3: 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 1 Month 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female infants ≥1 month and ≤24 months；
- •Diagnosis of RSV infection by antigen detection or nucleic acid within 36 hours preceding initial dosing；
- •Onset of RSV infection symptoms should be ≤ 5 days；
- •Patient must weigh ≥ 2.5 kg and ≤ 20 kg at screening；
- •Patient must have a Wang Respiratory Score ≥ 5;
- •Patient who are hospitalized or in emergency/outpatient department and are expected to be hospitalized;
- •The parent/legal guardian must have provided written informed consent for the patient to participate.
排除标准
- •Patients who are less than 12 months old and whose head circumference is not within the normal range corresponding to their age and gender at the time of screening;
- •Patients who have received prohibited used drugs (except external preparations) specified in the protocol for a specified time.
- •Requires vasopressors or inotropic support at the time of enrollment;
- •Patients with known SARS-CoV-2 infection, influenza virus infection, mycoplasma infection or bacterial infection；
- •Patients with hypercapnia (Except for patients who have recovered at the time of screening);
- •Chronic or persistent feeding difficulties;
- •Concurrent gastrointestinal conditions that could seriously, in the opinion of the investigator, prejudice absorption of the Investigational Medicinal Product;
- •Symptomatic because of inborn errors of metabolism;
- •Bronchopulmonary dysplasia requiring assisted ventilationor with clinically significant congenital respiratory abnormalities, except for the result of RSV infection;
- •Patients with congenital heart disease (CHD) with significant hemodynamic changes, except simple CHD (such as patent ductus arteriosus, atrial septal defect or ventricular septal defect without hemodynamic influence).
- •Clinical evidence of hepatic decompensation
- •Renal failure including renal anomalies likely to be associated with renal insufficiency;
- •Patient is known to be HIV-positive (or the mother, if the potential patient is a child aged <6 months);
- •Suspected or known to have congenital acquired immunodeficiency;
- •A history of epilepsy or seizures;
- •A history of high allergies;
- •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;
- •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.
研究组 & 干预措施
Deuremidevir Hydrobromide for Suspension
Deuremidevir Hydrobromide for Suspension will be orally administered at the dosing levels of 15 mg/kg BID, 20 mg/kg BID, or 20 mg/kg TID for five days according to the weight of patients.
干预措施: Deuremidevir Hydrobromide for Suspension (Drug)
Placebo
Placebo will be orally administered at the dosing levels of 15 mg/kg BID, 20 mg/kg BID, or 20 mg/kg TID for five days according to the weight of patients.
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of area under curve of viral load
时间窗: From baseline up to Day2-7 and Day14
The antiviral effects are to be determined by measuring the differences in area under curve (AUC).
Time to resolution of 6 clinical symptoms related to RSV infection
时间窗: From baseline through study completion, up to Day 14
Time to resolution of 6 clinical symptoms related to RSV infection
Time to resolution of individual clinical symptoms related to RSV infection
时间窗: From baseline through study completion, up to Day 14
Time to resolution of individual clinical symptoms related to RSV infection
Difference of the proportion of subjects with cough remission
时间窗: From baseline up to Day2-7 and Day14
Difference of the proportion of subjects with cough remission
Difference of the proportion of subjects with cough resolution
时间窗: From baseline up to Day2-7、Day14 and D26
Difference of the proportion of subjects with cough resolution
Proportions of subjects achieving symptom remission &disease remission
时间窗: From baseline up to Day2-7 and Day14
Symptom remission was defined as bronchiolitis score ≤1. Disease remission was defined as bronchiolitis score ≤1 and with no assisted ventilation.
Differences of frequency of Intensive Care Unit (ICU) admission
时间窗: From first treatment through study completion, up to Day 14
The differences of frequency of ICU admission between Deuterium Hydrobromide for suspension and placebo arms.
Incidence of Adverse Events during the study
时间窗: From baseline through study completion, up to Day 26
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 Adverse Events
时间窗: From baseline through study completion, up to Day 26
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.
Differences of length of ICU stay
时间窗: From first treatment through study completion, up to Day 14
The differences of length of ICU stay between Deuterium Hydrobromide for suspension and placebo arms.
Differences of the proportion of subjects with wheezing remission
时间窗: From baseline up to Day2-7 and Day14
Differences of the proportion of subjects with wheezing remission
Differences of the proportion of subjects with wheezing resolution
时间窗: From baseline up to Day2-7 and Day14
Differences of the proportion of subjects with wheezing resolution
Changes of bronchiolitis score
时间窗: From baseline up to Day2-7 and Day14
The differences of change in the bronchiolitis score are to be evaluated between the Deuterium Hydrobromide for suspension 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 from first treatment to symptom remission &disease remission
时间窗: From first treatment through study completion, up to Day 14
The time difference from the first treatment to the time subjects achieved symptom remission between the Deuterium Hydrobromide for suspension and placebo arms. The time difference from the first treatment to the time subjects achieved disease remission between the Deuterium Hydrobromide for suspension and placebo arms.
Differences of frequency of assisting ventilation
时间窗: From first treatment through study completion, up to Day 14
The frequency difference from the first treatment to the end of assisting ventilation therapy in subjects between the Deuterium Hydrobromide for suspension and placebo arms.
Changes of viral load
时间窗: From baseline up to Day2-7 and Day14
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 Deuterium Hydrobromide for suspension and placebo arms after treatment.
Differences in the duration of receiving oxygen therapy
时间窗: From first treatment through study completion, up to Day 14
The duration difference from the first treatment to the end of receiving oxygen therapy in subjects between the Deuterium Hydrobromide for suspension and placebo arms.
Apparent total body clearance (CL/F)
时间窗: From baseline up to Day2-7
Apparent clearance of of 116-N1.
Area under the plasma concentration time curve from time zero to the last(AUC0-t)
时间窗: From baseline up to Day2-7
Area under the plasma concentration time curve from time zero to the last of 116-N1.
apparent volume of distribution(V)
时间窗: From baseline up to Day2-7
Apparent volume of distribution during the terminal phase of 116-N1.
次要结局
- The correlation between viral load and the resolution time of 6 clinical signs related to RSV infection(From baseline up to Day2-7 and Day14)
- The correlation between viral load and bronchiolitis score(From baseline up to Day2-7and Day14)
- The effect of the duration of RSV infection onset to the first use of the investigational drug on the treatment efficacy (clinical signs、change in bronchiolitis score from baseline) in subjects(From baseline up to Day2-7 and Day14)
- The difference in length of hospital stay(From baseline up to Day2-7 and Day14)
- Proportions of subjects with viral load below LLOQ(From baseline up to Day2-7 and Day14)
- The correlation between AUC0-t （ Area under the plasma concentration time curve from time zero to the last）and the resolution time of clinical signs(From baseline up to Day2-7 and Day14)
- The correlation between AUC0-t （ Area under the plasma concentration time curve from time zero to the last）and bronchiolitis score and RSV viral load (VL) in respiratory sample(From baseline up to Day2-7 and Day14)