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

Respiratory Syncytial Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02135614
• Other study ID #: GS-US-218-1227
• Secondary ID: 2014-002137-58
• Status: Completed
• Phase: Phase 2
• Start date: June 9, 2014
• Est. completion date: April 12, 2017

Study information

• Verified date: May 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: April 12, 2017
• Est. primary completion date: March 27, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Respiratory Syncytial Virus Infection
• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Drug:
• Presatovir
Presatovir 200 mg (4 x 50 mg tablets) administered orally
• Presatovir placebo
Presatovir placebo tablets administered orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Israel,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Number of Hospitalization-Free Days Following Presatovir Administration		Up to Day 28
Secondary	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