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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: Placebo; Drug: ALS-008176

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Northmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Heal.-Monash Lung&Sleep
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• New Zealand
  • Wellington
    • Newtown, Wellington, New Zealand, 6021
      • Wellington Regional Hospital
• Singapore
  • Singapore, Singapore, 188770
    • Raffles Hospital
• Taiwan
  • New Taipei City, Taiwan, 235
    • Taipei Med. Uni-Shuang Ho Hosp
• United States
  • Florida
    • Eustis, Florida, United States, 32726
      • Lake Internal Med. Assoc.
    • Hialeah, Florida, United States, 33013
      • The Research Center, Inc.
    • Miami, Florida, United States, 33186
      • JDH Medical Group LLC
    • Port Saint Lucie, Florida, United States, 34952
      • St Lucie Medical Center
    • Tampa, Florida, United States, 33606
      • Tampa Genereal Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Lung Clinic, PSC
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hosp. Ped
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri- Clinical Research Center
    • Saint Louis, Missouri, United States, 63110
      • Washington Univ School of Med

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Identical Placebo Comparator	Drug: Placebo; Identical placebo tablets
Experimental: ALS-008176; ALS-008176 tablets	Drug: ALS-008176; ALS-008176 tablets

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

Collaborators and Investigators

• Sponsor: Alios Biopharma Inc.
• Investigators: Study Director: Abbie Oey, Alios Biopharma Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2016
• Primary Completion (Actual): October 31, 2016
• Study Completion (Actual): October 31, 2016

Study Registration Dates

• First Submitted: January 29, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 4, 2016

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: ALS-8176-510

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No