Respiratory Syncytial Virus Infections
Conditions
Brief summary
This study is being to see how effective and safe ALS-008176 is in treating adults in the hospital with a Respiratory Syncytial Virus-Related Illness.
Interventions
DRUGALS-008176
ALS-008176 tablets
DRUGPlacebo
Identical placebo tablets
Sponsors
Alios Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is ≥50 years of age. 2. Female subjects of non-childbearing potential (i.e., surgically sterilized, post-menopausal \[amenorrhea for 1 year confirmed by negative hormone panel\]) who also have a negative pregnancy test at screening. 3. Male subjects must be either surgically sterilized (e.g., post-vasectomy or orchiectomy) or willing to adhere to the study's contraceptive requirements. Male subjects'female partner(s) must be surgically sterilized or post-menopausal (amenorrhea for 1 year) or their female partner(s) of child-bearing potential must be willing and able to adhere to the contraceptive requirements. 4. Each subject or their legal guardian must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study before starting any screening activities. 5. Subject has a positive RT-PCR test result for RSV at the time of screening. NOTE: Co-infection with other acute viruses or bacteria is permitted. 6. Subject has been, or will be, admitted to the hospital for an acute respiratory illness with signs and symptoms consistent with a viral infection (e.g., fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset \<7 days from the anticipated time of randomization.
Exclusion criteria
1. Subject is undergoing peritoneal dialysis, hemodialysis or hemofiltration or has an estimated glomerular filtration rate (GFR, determined by Cockcroft-Gault Formula) \<30 mL/min. 2. Subject has presence of any concurrent illness, including laboratory, vital sign, ECG, or physical exam findings, or medical history that, in the opinion of the investigator, would place the subject at an unreasonably increased risk as a result of participation in this study. 3. Subject reports receiving an investigational drug or vaccine within 30 days, or 5 half-lives (whichever is longer) prior to the planned first dose of study drug. 4. Subject has a known history of human immunodeficiency virus (HIV) or chronic, active hepatitis infection. 5. ALT \>3×ULN AND bilirubin \>2×ULN (direct \>35%) OR ALT\>5×ULN 6. Subjects who have been hospitalized for \>72 hours at the time of randomization. 7. Subjects anticipated to be hospitalized for \<24 hours after randomization. 8. Subjects who are not expected to survive for \<48 hours. 9. Recent (\<5 half-lives) use, or anticipated use during conduct of the study, of concomitant medications (prescription and non-prescription) which are inhibitors of the OAT3 transporter. 10. Treatment of the current illness with drugs specifically targeting the RSV infection itself (e.g., RSV immunoglobulin, ribavirin, palivizumab). Medications treating the sequelae of the RSV infection or any concurrent illness are permitted if not otherwise excluded. 11. Subjects unwilling to undergo regular nasal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens. 12. Subjects that are considered by the investigator to be immunocompromised over the past 12 months, whether due to underlying medical condition or medical therapy. 13. Subjects unable to take medications enterally (e.g., orally or via nasogastric or PEG tube) or a known gastrointestinal-related condition that may interfere with study drug absorption. 14. Female subject that is pregnant or breastfeeding 15. In the investigator's opinion, the subject is unwilling or unable to comply with protocol requirements, instructions, and protocol stated restrictions, and is unlikely to complete the study as planned. 16. Subject has known or suspected hypersensitivity to the study drug or its excipients (microcrystalline cellulose, mannitol, croscarmellose sodium, magnesium stearate, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC of RSV RNA | From prior to first dose to study day 7 | Area under the curve (AUC) of RSV ribonucleic acid (RNA) from nasal swabs immediately prior to 1st dose of study drug (baseline) until Day 7. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of subjects with undetectable RSV by qPCR | From study day 3, and every two days until study day 7 | Percent of subjects with undetectable RSV by qPCR on Day 3, Day 5, and every other day until 2 days after last dose from nasal swab |
| Peak post-baseline viral load | From before first dose to study day 28 | Peak post-baseline viral load from nasal swab |
| Rate of decline from baseline in viral load during treatment from nasal swab | From before first dose to study day 2 | Rate of decline from baseline in viral load during treatment from nasal swab |
| Duration of hospital stay | From first dose to study day 28 | Duration of hospital stay |
| Safety data: Composite number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, echo and abnormal clinical laboratory results | From screening to study day 28 | Tabulation of the number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG, echo and abnormal clinical laboratory results (including chemistry, hematology, and urine). |
| Time from baseline to non-detectability of RSV from nasal swab | From prior first dose to study day 28 | Time from baseline to non-detectability of RSV from nasal swab |
| PK parameters: tmax | From first dose to study day 28 | PK parameters in plasma following repeat dose administration: tmax |
| PK parameters: AUClast | From first dose to study day 28 | PK parameters in plasma following repeat dose administration: AUClast |
| PK parameters: t1/2 | From first dose to study day 28 | PK parameters in plasma following repeat dose administration: t1/2 |
| PK parameters: AUC0 tau | From first dose to study day 28 | PK parameters in plasma following repeat dose administration: AUC0 tau |
| PK parameters: Cmax | From first dose to study day 28 | PK parameters in plasma following repeat dose administration: Cmax |
Countries
Australia, New Zealand, Singapore, Taiwan, United States
Outcome results
None listed