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

Phase 2
Completed
Conditions
Respiratory Syncytial Virus Infections
Interventions
Drug: Placebo
Drug: ALS-008176
Registration Number
NCT02673476
Lead Sponsor
Alios Biopharma Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9
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.
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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).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboIdentical Placebo Comparator
ALS-008176ALS-008176ALS-008176 tablets
Primary Outcome Measures
NameTimeMethod
AUC of RSV RNAFrom 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 Outcome Measures
NameTimeMethod
PK parameters: AUC0 tauFrom first dose to study day 28

PK parameters in plasma following repeat dose administration: AUC0 tau

Time from baseline to non-detectability of RSV from nasal swabFrom prior first dose to study day 28

Time from baseline to non-detectability of RSV from nasal swab

PK parameters: t1/2From first dose to study day 28

PK parameters in plasma following repeat dose administration: t1/2

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 resultsFrom 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).

PK parameters: tmaxFrom first dose to study day 28

PK parameters in plasma following repeat dose administration: tmax

Peak post-baseline viral loadFrom 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 swabFrom before first dose to study day 2

Rate of decline from baseline in viral load during treatment from nasal swab

Duration of hospital stayFrom first dose to study day 28

Duration of hospital stay

PK parameters: CmaxFrom first dose to study day 28

PK parameters in plasma following repeat dose administration: Cmax

PK parameters: AUClastFrom first dose to study day 28

PK parameters in plasma following repeat dose administration: AUClast

Percent of subjects with undetectable RSV by qPCRFrom 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

Trial Locations

Locations (21)

Raffles Hospital

🇸🇬

Singapore, Singapore

St Lucie Medical Center

🇺🇸

Port Saint Lucie, Florida, United States

The Research Center, Inc.

🇺🇸

Hialeah, Florida, United States

University of Missouri- Clinical Research Center

🇺🇸

Columbia, Missouri, United States

JDH Medical Group LLC

🇺🇸

Miami, Florida, United States

Infectious Disease Specialists of Atlanta

🇺🇸

Atlanta, Georgia, United States

Kentucky Lung Clinic, PSC

🇺🇸

Hazard, Kentucky, United States

Bronson Methodist Hosp. Ped

🇺🇸

Kalamazoo, Michigan, United States

William Beaumont Hospital

🇺🇸

Troy, Michigan, United States

Westmead Hospital

🇦🇺

Northmead, New South Wales, Australia

Mater Adult Hospital

🇦🇺

South Brisbane, Queensland, Australia

The Queen Elizabeth Hospital

🇦🇺

Woodville South, South Australia, Australia

Monash Heal.-Monash Lung&Sleep

🇦🇺

Clayton, Victoria, Australia

The Royal Melbourne Hospital

🇦🇺

Parkville, Victoria, Australia

Wellington Regional Hospital

🇳🇿

Newtown, Wellington, New Zealand

Taipei Med. Uni-Shuang Ho Hosp

🇨🇳

New Taipei City, Taiwan

Washington Univ School of Med

🇺🇸

Saint Louis, Missouri, United States

Tampa Genereal Hospital

🇺🇸

Tampa, Florida, United States

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

Cairns Hospital

🇦🇺

Cairns, Queensland, Australia

Lake Internal Med. Assoc.

🇺🇸

Eustis, Florida, United States

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