Respiratory Syncytial Virus Infection MedDRA version: 20.1 Level: PT Classification code 10061603 Term: Respiratory syncytial virus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: ALS-008176
Product Code: ALS-008176
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: N/A
CAS Number: 1
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female infant who is =28 days to =36 months of age, inclusive, 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 a PCR-based molecular diagnostic assay (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) with or without co-infection with another respiratory pathogen (eg, influenza, human metapneumovirus, or bacteria). 4. The time of onset of RSV symptoms to the time of randomization must be =5 days. Onset of symptoms is defined as the first time (within 1 hour) the parent(s)/caregiver(s) becomes aware of respiratory or systemic symptoms of RSV infection. At the recommendation of the IDMC, this duration may be decreased or increased to up to 7 days. If this occurs, the Independent Ethics Committees (IECs)/Institutional Review Boards (IRBs) will be notified promptly, without the need for a formal protocol amendment. 5. With the exception of the RSV-related illness or defined comorbid condition for severe RSV bronchiolitis (prematurity at birth [for infants =65 years) no F.1.3.1 Number o
Exclusion criteria
Exclusion criteria: 1. Subject has known or suspected immunodeficiency (except immunoglobulin A [IgA] deficiency), such as known human immunodeficiency virus infection. 2. Receipt of (within the last 12 months) or currently on a waiting list for a bone marrow, stem cell or solid organ transplant, receipt of radiation or chemotherapy within 12 months prior to screening, or currently taking immunosuppressive medication. 3. Subjects who are anticipated to be treated with other agents with potential antiviral activity against RSV (eg, ribavirin, IV immunoglobulin, palivizumab). 4. History of or concurrent illness (beyond a defined comorbid condition for severe RSV bronchiolitis) that in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit, or confound the protocol-specified assessments such as liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, metabolic disturbances, or genetic diseases that result in immunosuppression. These may include, but are not limited to bacteremia, organ dysfunction, or other severe comorbidities. 5. Poorly functioning gastrointestinal tract (ie, unable to absorb drugs or nutrition via enteral route). Note: the use of IV fluids is not exclusionary so long as the investigator believes the subject’s gastrointestinal tract still functions properly (ie, is able to absorb drugs or nutrition). 6. Subject is being treated with extracorporeal membrane oxygenation. 7. Subject receiving chronic oxygen therapy at home prior to admission. 8. Taking any disallowed therapies before the planned first dose of study drug. 9. Received an investigational drug, an investigational vaccine, or used an invasive investigational medical device within 30 days or 5 half-lives (whichever is longer) before the planned first dose of study drug or is currently enrolled in an investigational study. 10. Planned or current participation in another interventional clinical study during this study. 11. Known allergies, hypersensitivity, or intolerance to ALS-008176 or its excipients. 12. Being breastfed by a mother taking any of the excluded medications. 13. Subject’s legally acceptable representative ie, parent(s)/legal guardian/caregiver(s), is not able to communicate reliably with the investigator. 14. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine in infants and children who are hospitalized with RSV infection the dose-response relationship of multiple regimens of ALS-008176 on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase polymerase chain reaction [qRT-PCR] assay.; Secondary Objective: The secondary objectives are to determine in infants and children who are hospitalized with RSV infection: • The impact of ALS-008176 on the clinical course of RSV infection including: - Duration of hospital stay. - Duration of supplemental oxygen. - Clinical assessments (including clinician Clinical Outcome Assessment [COA]). - Time to clinical stability. • The time to cessation of nasal RSV shedding. • The impact of ALS-008176 on the emergence of resistant strains of RSV. • The safety and tolerability of ALS-008176. • The PK of ALS-008112 and ALS-008144 (and other metabolites, if applicable) in whole blood. • The relationship between the PK and the PD (antiviral activity, clinical symptoms, and selected safety parameters) after single (LD) and repeated oral dosing (MD) of ALS 008176. • The acceptability and palatability of the ALS-008176 formulation. ; Timepoint(s) of evaluation of this end point: Immediately prior to first dose of study drug (baseline) until 1 day (+2 days) after the last dose of study drug. ; Primary end point(s): The primary endpoint is RSV RNA viral load (measured by qRT-PCR in mid-turbinate nasal swab specimens) AUC from immediately prior to first dose of study drug (baseline) until Day 7. NOTE: If the dosing duration is increased by the IDMC to up to 10 days, the RSV RNA viral load AUC in subjects assigned to the longer dose duration will | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: As described in end points.; Secondary end point(s): The secondary endpoints are: • 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). - Respiratory rate, peripheral capillary oxygen saturation (SpO2), and body temperature return to pre-RSV disease level. - Number of hours until SpO2 =93% on room air among subjects who were not on supplemental oxygen prior to current hospitalization. - Need for and duration of noninvasive ventilator support (eg, continuous positive airway pressure) and/or invasive ventilator support (eg, endotracheal-mechanical ventilation). - Evolution of signs and symptoms of RSV disease as assessed by the clinician COA. - Amount of food intake, hydration, and feeding by IV administration/enteral tube. - Time to clinical stability defined as the time at which the following criteria are all met: - normalization of blood oxygen level (return to baseline, by pulse oximetry) without requirement of supplemental oxygen beyond baseline level - intravenous or enteral tube feeding/hydration no longer required - normalization of respiratory rate - normalization of heart rate • RSV RNA viral load as measured by qRT-PCR in the mid-turbinate nasal swab specimens, which will be used to determine the following: - Viral load over time | — |
Countries
Australia, Brazil, Canada, Chile, Czech Republic, Denmark, Estonia, Finland, France, Hungary, Ireland, Israel, Japan, Korea, Democratic People's Republic of, Malaysia, New Zealand, Panama, Poland, Portugal, Singapore, Slovakia, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactGuy De La Rosa, MD
Janssen Research & Development, LLC
Outcome results
None listed