A Phase 2a Study to Evaluate Orally Administered ALS-008176 in Adults Hospitalized With a Respiratory Syncytial Virus

Study Overview
=================
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.

Official Title
-----------------
A Phase 2a, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Orally Administered ALS-008176 in Adults Hospitalized With a Respiratory Syncytial Virus-Related Illness

Conditions
-----------------
Respiratory Syncytial Virus Infections

Intervention / Treatment
-----------------
* Drug: ALS-008176
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is ≥50 years of age. 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. 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. 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. 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. 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: Subject is undergoing peritoneal dialysis, hemodialysis or hemofiltration or has an estimated glomerular filtration rate (GFR, determined by Cockcroft-Gault Formula) <30 mL/min. 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. 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. Subject has a known history of human immunodeficiency virus (HIV) or chronic, active hepatitis infection. ALT >3×ULN AND bilirubin >2×ULN (direct >35%) OR ALT>5×ULN Subjects who have been hospitalized for >72 hours at the time of randomization. Subjects anticipated to be hospitalized for <24 hours after randomization. Subjects who are not expected to survive for <48 hours. 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. 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. Subjects unwilling to undergo regular nasal swab procedures or with any physical abnormality which limits the ability to collect regular nasal specimens. Subjects that are considered by the investigator to be immunocompromised over the past 12 months, whether due to underlying medical condition or medical therapy. 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. Female subject that is pregnant or breastfeeding 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. 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).

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Identical Placebo Comparator | Drug: Placebo<br>* Identical placebo tablets<br>|
| Experimental: ALS-008176<br>ALS-008176 tablets | Drug: ALS-008176<br>* ALS-008176 tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of RSV RNA | 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. | From prior to first dose to study day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from baseline to non-detectability of RSV from nasal swab | Time from baseline to non-detectability of RSV from nasal swab | From prior first dose to study day 28 | 
| Percent of subjects with undetectable RSV by qPCR | 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 | From study day 3, and every two days until study day 7 | 
| Peak post-baseline viral load | Peak post-baseline viral load from nasal swab | From before first dose to study day 28 | 
| Rate of decline from baseline in viral load during treatment from nasal swab | Rate of decline from baseline in viral load during treatment from nasal swab | From before first dose to study day 2 | 
| Duration of hospital stay | Duration of hospital stay | From first dose to study day 28 | 
| 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 | 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). | From screening to study day 28 | 
| PK parameters: Cmax | PK parameters in plasma following repeat dose administration: Cmax | From first dose to study day 28 | 
| PK parameters: tmax | PK parameters in plasma following repeat dose administration: tmax | From first dose to study day 28 | 
| PK parameters: AUClast | PK parameters in plasma following repeat dose administration: AUClast | From first dose to study day 28 | 
| PK parameters: t1/2 | PK parameters in plasma following repeat dose administration: t1/2 | From first dose to study day 28 | 
| PK parameters: AUC0 tau | PK parameters in plasma following repeat dose administration: AUC0 tau | From first dose to study day 28 |