Respiratory Syncytial Virus Infection (RSV) viral infection
Conditions
Interventions
Part 1
A target of approximately 24 subjects with a maximum of 36 subjects will be
randomized in a 1:2 ratio to Regimen A or B:
* Regimen A (placebo): a single LD (Dose 1) followed by 9 MDs (Doses 2
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Men or women *18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, defined at the time of randomization.;2. Hospitalized (or in emergency room prior to hospitalization) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization. ;3. Diagnosed with RSV infection based on PCR-based assay with or without co-infection with another respiratory pathogen (eg, influenza,human metapneumovirus, or bacteria). NOTE: in cases where commercial PCR-based assays are not available at the site, the sponsor should be consulted for agreement on the assay to be used. ;4. Has an acute respiratory illness with signs and symptoms consistent with a viral infection (eg, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset *5 days from the anticipated time of randomization.;NOTE: The viral infection may present in any way as long as the underlying precipitant of the illness is considered by the investigator to be due to RSV infection. Examples of such an illness include: * An upper or lower viral respiratory tract infection (eg, *flu-like illness*) * Pneumonia * Respiratory distress * Asthma exacerbation * Chronic obstructive pulmonary disease (COPD) exacerbation;5. With the exception of the RSV disease, medically stable on the basis of medical history, physical examination, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population and/or the RSV infection. This determination must be recorded in the subject*s source documents and initialed by the investigator.;6. Medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal do not pose an unacceptable risk to the subject, are not clinically significant, or are appropriate and reasonable for the population under study. This determination must be recorded in the subject*s source documents and initialed by the investigator. A single repeat laboratory evaluation is allowed for eligibility determination.;7. Must sign an ICF (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.;8. A woman must have a negative urine ß-human chorionic gonadotropin at screening.;9. Contraceptive use by women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. ;Before randomization, a woman must be either: a. Not of childbearing potential defined as: * Postmenopausal: a postmenopausal state is defined as >45 years and no menses for 12 consecutive months without an alternative medical cause, OR * Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy.;b. Of childbearing potential and, if heterosexually active, * Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) Examples
Exclusion criteria
Exclusion criteria: 1. Subjects who are not expected to survive for more than 48 hours.;2. Subjects who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization.;3. Subjects who are considered by the investigator to be immunocompromised within the past 12 months, whether due to underlying medical condition (eg, malignancy or genetic disorder) or medical therapy (eg, medications other than corticosteroids for the treatment of COPD or asthma exacerbations,, chemotherapy, radiation, stem cell or solid organ transplant).;4. Subjects with a known history of human immunodeficiency virus (HIV) or chronic viral hepatitis.;5. Subjects with ALT *3 times the upper limit of normal (ULN) AND bilirubin *2×ULN (direct >35%) OR ALT *5×ULN at screening. ;6. Subjects undergoing peritoneal dialysis, hemodialysis, or hemofiltration or with an estimated glomerular filtration rate (GFR, determined by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) of 7 consecutive days immediately prior to randomization at doses higher than 20 mg/day of prednisone or e
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For Part 1: The primary endpoint is the PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in plasma. For Part 2: The primary endpoint is RSV RNA viral load (measured by qRT-PCR in the mid-turbinate nasal swab specimens) area under the curve (AUC) from immediately prior to first dose of study drug (baseline) until Day 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints The secondary endpoints for part 1 and part 2 are: * Safety/tolerability including adverse events (AEs), physical examinations, vital signs, electrocardiograms (ECGs), and clinical laboratory results. * RSV clinical course endpoints: - Length of hospital stay from admission to discharge and from study treatment initiation to discharge. - Length of hospital stay from admission to readiness for discharge and from study treatment initiation to readiness for discharge, with readiness for discharge defined by the investigator. - Need for and duration of intensive care unit (ICU) stay. - Need for and duration of supplemental oxygen (regardless of method used). - Number of hours until peripheral capillary oxygen saturation (SpO2) *93% on room air among subjects who were not on supplemental oxygen prior to the onset of respiratory symptoms.. - Respiratory rate, SpO2, and body temperature return to pre-RSV disease level. - Need for and duration of noninvasive ventilator support (eg, continuous positive airway pressure) and/or invasive ventilator support (eg, endotracheal-mechanical ventilation or mechanical ventilation via tracheostomy). - Time to return to pre-RSV functional status (Katz ADL score). - Need for hydration and feeding by intravenous (IV) catheter/nasogastric tube. - Time to clinical stability defined as the time at which the following criteria are all met: o normalization of blood oxygen level (return to baseline; by pulse oximetry) without requirement of supplemental oxygen beyond baseline level o normalization of oral feeding o normalization of respiratory rate o normalization of heart rate - Improvement on the ordinal scale. - All-cause mortality. * RSV RNA viral load as measured by qRT-PCR of the mid-turbinate nasal swab specimens which will be used to determine the following: - Viral load over time. - Peak viral load, time to peak viral load, rate of decline of viral load, and time to RSV RNA being und | — |
Countries
Netherlands
Outcome results
None listed