Efficacy, Pharmacokinetics, and Safety of Presatovir in Hospitalized Adults With Respiratory Syncytial Virus (RSV) Infection

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hospitalized Adults With Respiratory Syncytial Virus (RSV) Infection

The primary objective of this study is to evaluate the effects of presatovir on respiratory syncytial virus (RSV) viral load in RSV-positive adults who have been hospitalized with acute respiratory infectious symptoms.

Participants will receive 1 dose of presatovir on Day 1 and followed for 27 days postdose. Nasal swabs will be collected at each study visit (excluding Day 28) and assayed for change in viral load as the primary endpoint.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infection
• Intervention / Treatment: Drug: Presatovir; Drug: Presatovir placebo

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia
      • John Hunter Hospital
    • Westmead, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Redcliffe, Queensland, Australia
      • Redcliffe Hospital
    • Southport, Queensland, Australia
      • Gold Coast Hospital
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Medical Center
    • Frankston, Victoria, Australia
      • Frankston Hospital
• Belgium
  • Anderlecht, Belgium
    • Universite Liebre de Bruxelles - Hopital Erasme
• France
  • Brest, France
    • CHRU Brest - Hospital Cavale Blanche
  • Clamart, France
    • Hopital d'Instructions des Armees Percy
  • Colombes, France
    • Hôpital Louis Mourier
  • Paris, France
    • Hopital Tenon
  • Paris, France
    • Hopital Saint Louis - Service de Pneumologie
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France
      • Hopital Foch
• Israel
  • Beer Sheva, Israel
    • Soroka Medical Center
  • Holon, Israel
    • Edith Wolfson Medical Center
  • Jerusalem, Israel
    • Hadassah University Hospital Ein Kerem
  • Kefar-Sava, Israel
    • Meir Medical Center
  • Nahariya, Israel
    • Western Galilee Hospital-Nahariya
  • Nazareth, Israel
    • The Nazareth hospital
  • Petah Tikva, Israel
    • Rabin Medical Center
  • Ramat Gan, Israel
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel
    • Sourasky Medical Center
• Italy
  • Milano, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Soon Chun Hyang University Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
• Netherlands
  • Zutphen, Netherlands
    • Gelre Ziekenhuizen
• New Zealand
  • Auckland, New Zealand
    • Middlemore Hospital
  • Hamilton, New Zealand
    • Waikato Hospital
  • Bay Of Plenty
    • Tauranga, Bay Of Plenty, New Zealand
      • Tauranga Hospital
• Poland
  • Wroclaw, Poland
    • Centrum Badan Klinicznych
• United Kingdom
  • Southampton, United Kingdom
    • Southampton University Hospitals NHS Trust
  • Telford, United Kingdom
    • Princess Royal Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States
      • Northwestern Memorial Hospital
  • Maryland
    • Annapolis, Maryland, United States
      • Anne Arundel Medical Center
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Health System
    • Royal Oak, Michigan, United States
      • William Beaumont
  • New York
    • New York, New York, United States
      • New York Presbyterian Hospital
    • Rochester, New York, United States
      • Rochester General Hospital
  • Tennessee
    • Nashville, Tennessee, United States
      • Vanderbilt Medical Group and Clinic
  • Washington
    • Seattle, Washington, United States
      • University of Washington
  • Wisconsin
    • Marshfield, Wisconsin, United States
      • Marshfield Clinic Research Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Current inpatient

• New onset of acute respiratory infectious symptoms, or acute worsening of chronic symptoms related to ongoing respiratory disease for ≤ 5 days prior to screening:

  • Upper respiratory tract symptoms: nasal congestion, runny nose, sore throat, or earache
  • Lower respiratory tract symptoms: cough, sputum production, wheezing, dyspnea, or chest tightness
• Documented to be RSV-positive at the current admission within 72 hours of screening, or as evaluated at screening

Key Exclusion Criteria:

• Related to concomitant or previous medication use:

  • Use of oral prednisone or other corticosteroid equivalent to:

    • > 20 mg/day for > 14 days prior to screening is not permitted.
    • > 20 mg/day for ≤ 14 days, including corticosteroids received during current hospitalization (ie, bolus doses), is permitted.
    • ≤ 20 mg/day, regardless of duration, is permitted.
  • Individuals taking a moderate or strong cytochrome P450 enzyme (CYP) inducer including but not limited to rifampin, St John's Wort, carbamazepine, phenytoin, efavirenz, bosentan, etracirine, modafinil, and nafcillin within 2 weeks prior to the first dose of study drug

• Related to medical history:

  • Pregnant, breastfeeding, or lactating females
  • Individuals requiring > 50% supplemental oxygen (while the individual is awake) at screening
  • Individuals with a Clinical Frailty Scale (CFS) > 7 at Baseline
  • Known significant abnormality altering the anatomy of the nose or nasopharynx that in, the opinion of the investigator, will preclude obtaining adequate nasal swab sampling in either nasal passage
  • Waiting for or recently (within the past 12 months) received a bone marrow, stem cell, or solid organ transplant, or who have received radiation or chemotherapy within 12 months prior to Screening
  • Individuals with HIV/AIDS and a known CD4 count < 200 cells/uL
  • History of severe dementia or Alzheimer's disease
  • History of drug and/or alcohol abuse that, in the opinion of the investigator, may prevent adherence to study activities

• Related to medical condition at screening:

  • Influenza-positive as determined by local diagnostic test
  • Known Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection or known coinfection with other coronavirus
  • Use of mechanical ventilation during the current admission, not including noninvasive ventilation
  • Clinically significant bacteremia or fungemia that has not been adequately treated prior to Screening, as determined by the investigator
  • Inadequate treatment of confirmed bacterial, fungal, or non-RSV pneumonia, as determined by the investigator
  • Excessive nausea/vomiting at admission, as determined by the investigator, that precludes administration of an orally administered study drug

• Related to allergies:

  • Known allergy to components of the study drug (microcrystalline cellulose, mannitol, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol and talc)
  • Documented history of acute (anaphylaxis) or delayed (Stevens-Johnson syndrome or epidermal necrolysis) allergy to sulfa drugs

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Presatovir; Participants will receive a single dose of presatovir.	Drug: Presatovir; Presatovir 200 mg (4 x 50 mg tablets) administered orally; Other Names: GS-5806
PLACEBO_COMPARATOR: Presatovir placebo; Participants will receive a single dose of presatovir placebo.	Drug: Presatovir placebo; Presatovir placebo tablets administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-Weighted Average Change in Respiratory Syncytial Viral (RSV) Load From Baseline to Day 5	The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.	Baseline to Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Average Change in the Flu-PRO Score From Baseline to Day 5	The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms). The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.	Baseline to Day 5
Number of Hospitalization-Free Days Following Presatovir Administration		Up to Day 28
Rate of Unplanned Medical Encounters	The adjusted rate of unplanned medical encounters (clinic visits, emergency room visits, urgent care visits, and rehospitalizations) related to a respiratory illness after initial hospital discharge through Day 28 will be assessed. Event rate was calculated as the total number of unplanned medical encounters divided by the total number of participants. The mean values presented were adjusted for stratification factor.	Up to Day 28

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 9, 2014
• Primary Completion (ACTUAL): March 27, 2017
• Study Completion (ACTUAL): April 12, 2017

Study Registration Dates

• First Submitted: May 8, 2014
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (ESTIMATE): May 12, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 24, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Disease Attributes; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Respiratory Syncytial Virus Infections
• Other Study ID Numbers: GS-US-218-1227; 2014-002137-58 (EUDRACT_NUMBER)

Drug and device information, study documents

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