Respiratory Syncytial Virus Infections
Conditions
Keywords
Adult patient with RSV infection, High-risk disease, AK0529
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter, phase II study to be conducted in adults hospitalized with RSV infection in China. The main objectives of this study are to investigate the safety, pharmacokinetics and efficacy of AK0529 in adult RSV patients.
Interventions
DRUGAK0529
Active Substance: AK0529, Pharmaceutical Form: Enteric pellets, Route of Administration: Oral, fasting
DRUGPlacebo
Active Substance: Placebo, Pharmaceutical Form: Enteric pellets, Route of Administration: Oral with meal or fasting
Sponsors
Shanghai Ark Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-Blind
Intervention model description
This clinical study is a randomized placebo controlled parallel multi-center phase II trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion criteria: 1. . Male or female patients of any ethnicity with an age of 18-85 years. 2. . Diagnosis of RSV infection by any virological means within 36 hours preceding initial dosing. 3. . At least one of the following high-risk diseases or states for RSV infection 1. Asthma or chronic lung disease (such as COPD or cystic fibrosis), 2. immunocompromised, 3. Heart disease (such as congenital heart disease, congestive, heart failure, or coronary artery disease), except high blood, pressure without heart-related symptoms, 4. Chronic kidney disease, 5. Age ≥65 years old. 4. . With at least 1 new onset respiratory infection symptom or exacerbation of existing respiratory symptoms (respiratory symptoms include: sore throat, nasal congestion, runny nose, sneezing, coughing, wheezing, sputum production, shortness of breath), and any individual score is 2 or moderate. 5. . Onset of RSV infection symptoms should be ≤ 7 days. Main
Exclusion criteria
1. . 3 days for drugs with potential antiviral effects on RSV such as ordinary interferon, 8 days for long-acting interferon, and 35 days for ribavirin for 5 half-lives before expected administration. 2. . Prohibited medicine are being used or planned to be used during the study treatment periods. 3. . Severe gastrointestinal diseases that affect the absorption of study drugs (such as vomiting, malabsorption syndrome, short bowel syndrome due to necrotizing enterocolitis, etc.). 4. . Received or planned to have bone marrow transplantation, stem cell transplantation or solid organ transplantation within 1 year. 5. . Patients with malignant tumors who had surgery within recent 6 months and/or requiring radiotherapy, chemotherapy and biological immunotherapy. 6. . Patients with autoimmune diseases who are in the induction treatment. 7. . HIV infection, CD4 count\< 350 cells/mm3 with opportunistic infection and need treatment. 8. . Other patients who are judged by the investigator to be unsuitable for participating in the study, such as acute/chronic heart, lung, liver, kidney, rheumatic immunity, psychiatric, blood and other diseases in the unstable period. 9. . History of drug abuse within 12 months prior to screening. 10. . Allergy to the investigational drug or its component. 11. . Female patients with positive pregnancy test or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of AE and SAE of subjects during the study period | Baseline up to 28 days | An Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect, or another important medical event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in RiiQ symptoms of subjects at each visit after treatment measured by RiiQ questionnaire | Baseline up to 28 days | RiiQ questionnaire is mainly used to assess RSV symptoms in patients, including upper respiratory tract infection symptoms (sore throat and nasal congestion), symptoms of lower respiratory tract infection (cough, wheezing, sputum, shortness of breath), and system symptoms (fever, headache, neck pain, fatigue, lack of appetite, interrupted sleep, body aches). The questionnaire is divided into four grading categories of severity including none (0), mild (1), moderate (2) and severe (3). |
| Changes from baseline in the total score of RSV Symptom of subjects at each visit after treatment using RSV Symptom Score Composite Scale | Baseline up to 28 days | RSV Symptom Score Composite Scale is used to assess patients with RSV symptoms, including runny nose, stuffy nose, sneezing, sore throat, earache, cough, shortness of breath, headache, fatigue, myalgia and/or joint pain. The score is divided into 4 grades according to the severity of symptoms. 0 indicates no symptoms, 1 indicates occasional symptoms, 2 indicates that symptoms sometimes worsen significantly but do not affect daily activities, and 3 indicates that symptoms are always serious and cannot engage in daily activities. The total score is 30 points. |
| Changes from baseline in the RSV VL (viral load) of subjects at each visit after treatment | Baseline up to 28 days | The RSV VL of subjects' nasopharyngeal samples is measured as Log10 copies/mL by quantitative reverse transcription polymerase chain reaction (qRT-PCR). |
| Area under the curve (AUCE, last) of RSV Viral Load from baseline to the last measurement | Baseline up to 28 days | The RSV VL is measured as Log10 copies/mL by qRT-PCR assay in the nasopharyngeal specimens. |
| Number of subjects with RSV VL values below the lower limit of quantitation (LLOQ) at each visit after treatment | Baseline up to 28 days | The RSV VL is measured as Log10 copies/mL by qRT-PCR assay in the nasopharyngeal specimens. |
| Number of participants who dropped out of the study due to AE | Baseline up to 28 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Number of participants with laboratory examination abnormalities | Baseline up to 28 days | Following parameters were analyzed for laboratory examination: hemoglobin (Hb), hematocrit, platelet count, red blood cell (RBC) count, white blood cell (WBC) count, mean corpuscular volume (MCV) and absolute white blood cell line (neutrophils, eosinophils, lymphocytes, monocytes, basophils); Hepatobiliary biochemistry: total and direct bilirubin, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP); Renal Function Tests: creatinine kinase, uric acid ; Electrolytes: Sodium, Potassium; Glucose; Coagulation function (subjects with only a history of liver disease should be tested): international normalized ratio (INR), activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen; Urine analysis: urine protein, ketone bodies, urine red blood cells, urine white blood cells, and urine glucose; Blood or urine pregnancy test for all female subjects. |
| Number of participants with vital sign abnormalities | Baseline up to 28 days | Number of participants with vital sign (systolic and diastolic blood pressure, pulse rate, respiratory rate, temperature and oxygen saturation) abnormalities were reported. |
| Change from baseline in clinical improvement score of subjects at each visit after treatment by clinical improvement scale | Baseline up to 28 days | Clinical improvement scale is mainly used to evaluate the overall severity level of the subject's disease with the highest score of 8 indicating death. A score of 6-7 represents severe hospitalization: a score of 6 requires mechanical ventilation, and a score of 7 requires not only mechanical ventilation but also angiogenic treatment, kidney dialysis, or artificial membrane lung. A score of 3-5 represents mild hospitalization: a score of 3 does not require oxygen therapy, a score of 4 requires a mask or nasal catheter, and a score of 5 requires noninvasive positive pressure ventilation or high-flow oxygen therapy. A score of 1-2 represents outpatient treatment: 1 is independent and 2 is in need of care (daily activities have an impact). A score of 0 means no treatment is required and there is no clinical or virological evidence of infection. |
| Number of participants with ECG abnormalities | Baseline up to 28 days | Electrocardiograms were measured during the screening period, at 4 (±1) hours after the first dose on day 2, at 4 (±1) hours and 12 (±1) hours (before the second dose) after the first dose on day 4, and once on day 6 and day 14 during the follow-up period; 9-or 12-lead ECG results are recorded using an ECG instrument which automatically calculates heart rate and measures PR, QRS, QT and QTc intervals. |
| Peak Plasma Concentration (Cmax) | Day 1, Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Time to Maximum Plasma Concentration (Tmax) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Terminal Elimination Half-life (t½) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Apparent Clearance (CL/F) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Apparent Volume of Distribution (V[z]/F) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Area Under the Plasma Concentration-Time Curve From Time 0 to 12 (AUC[0-12]) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC[0-∞]) | Day 1，Day 5 | Whole blood of subjects (2 mL per time point) was collected for the concentration determination of the AK0529 and its metabolites at various time points on day 1 and day 5, and the PK parameter is calculated using the above-mentioned plasma concentration data. |
| Number of participants with physical examination abnormalities | Baseline up to 28 days | A comprehensive physical examination includes at least cardiovascular, respiratory, gastrointestinal, and nervous system assessments; a simple physical examination includes at least skin, lung, cardiovascular system and abdominal (liver and spleen) assessments. |
Countries
China
Outcome results
None listed