A Phase 2 clinical trial investigating the anti-virus effects, kinetics and safety of GS-5806 in adults with RSV (Respiratory Syncytial Virus) infection.

• Register: EUCTR
• Last refreshed on: 8 January 2018
• Main ID: EUCTR2014-002474-36-NL
• Date of registration: 04/12/2014
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A Phase 2 clinical trial investigating the anti-virus effects, kinetics and safety of GS-5806 in adults with RSV (Respiratory Syncytial Virus) infection.
• Scientific title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients with Respiratory Syncytial Virus (RSV) Infection of the Upper Respiratory Tract.
• Date of first enrolment: 10/02/2015
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002474-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Canada, France, Germany, Israel, Japan, Korea, Republic of, Netherlands, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male and female subjects 18 to 75 years of age. In Japan subjects must be 20 to 75 years of age. In Singapore subjects must be
21 to 75 years of age
2. Received an autologous or allogeneic HCT using any conditioning
regimen
3. Documented to be RSV-positive as determined by local testing (eg,
PCR, DFA, RVP assay, or culture) using an upper respiratory tract sample collected = 6 days prior to Day 1 or as determined at Screening as per Section 6.1.1
4. New onset of at least 1 of the following respiratory symptoms for = 7 days prior to Day 1: nasal congestion, runny nose, cough, or sore throat, or worsening of one of these chronic (associated with a previously existing diagnosis, eg, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms = 7 days prior to Day 1
5. No evidence of new abnormalities consistent with LRTI on a chest Xray relative to the most recent chest X-ray, as determined by the local radiologist. If a chest X-ray is not available or was not obtained during standard care < 48 hours prior to Screening, a chest X-ray must be obtained for Screening
6. O2 saturation = 92% on room air
7. An informed consent document signed and dated by the subject or a legal guardian of the subject and the investigator or his/her designee. In Sweden ICFs signed by a legal guardian must also be signed by a close relative of the subject
8. A negative urine or serum pregnancy test is required for female
subjects (unless surgically sterile or greater than two years postmenopausal)
9. Male and female subjects of childbearing potential must agree to
contraceptive requirements as described in Appendix 5
10. Willingness to complete necessary study procedures and have
available a working telephone or email
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion criteria:
Related to concomitant or previous medication use:
1. Use of non-marketed (according to region) investigational agents within 30 days, OR use of any investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of Screening, whichever is longer, OR use of any investigational RSV vaccines after HCT.
2. Use of a moderate or strong cytochrome P450 enzyme (CYP) inducer including but not limited to rifampin, St. John’s Wort, carbamazepine, phenytoin, efavirenz, bosentan, etravirine, modafinil, and nafcillin, within 2 weeks prior to the first dose of IMP
Related to medical history:
3. Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the investigator
4. Pregnant, breastfeeding, or lactating females
5. Unable to tolerate nasal sampling required for this study, as determined by the investigator
6. Known history of HIV/AIDS with a CD4 count <200 cells/µL within the last month
7. 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:
8. Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus) within 7 days prior to the Screening visit, as determined by local testing (additional testing is not required)
9. Clinically significant bacteremia or fungemia within 7 days prior to Screening that has not been adequately treated, as determined by the investigator
10. Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated, as determined by the investigator
11. Excessive nausea/vomiting at Screening, as determined by the investigator, or an inability to swallow pills that precludes oral administration of the IMP (for subjects without an NG tube in place)
12. Any condition which, in the opinion of the investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints
Related to allergies:
13. Known hypersensitivity or allergy to the IMP, its metabolites, or formulation excipients (microcrystalline cellulose, mannitol, croscarmellose sodium, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol and talc)
14. History of hypersensitivity, anaphylactic reaction, Stevens-Johnson Syndrome, or toxic epidermal necrolysis response to sulfa drugs
Related to laboratory results:
15. Creatinine clearance < 30 mL/min (calculated using the Cockcroft-Gault method)
16. Clinically significant ALT/AST, as determined by the investigator
17. Clinically significant TB, as determined by the investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Virus (RSV) Infection of the upper respiratory tract.
MedDRA version: 19.0 Level: LLT Classification code 10039247 Term: RSV infection System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: GS-5806
Product Code: GS-5806
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: presatovir
CAS Number: 1353625-73-6
Current Sponsor code: GS-5806
Other descriptive name: GS-5806
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To evaluate the effect of presatovir on progression to respiratory
failure, or all-cause mortality
- To evaluate the PK, safety, and tolerability of presatovir

Timepoint(s) of evaluation of this end point: Change in nasal RSV viral load: Day 1 to day 9 (daily measure)
Development of LRTC: day 28

Main Objective: co-primary objectives of this study are:
To evaluate the effect of presatovir on RSV viral load and development of LRTC in RSV-positive autologous or allogeneic HCT recipients with acute URTI symptoms

Primary end point(s): The co-primary endpoints are:
Time-weighted average change in nasal RSV viral load (log10
copies/mL) from Baseline (Day 1) to Day 9 as measured by RT-qPCR
Proportion of subjects who develop a LRTC through Day 28, defined as one of the below, as determined by the adjudication committee:
-Primary RSV LRTI
-Secondary bacterial LRTI
-Lower respiratory tract infection due to unusual
pathogens
-Lower respiratory tract complication of unknown
etiology

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 28.

Secondary end point(s): Proportion of subjects who develop a LRTC through Day 28, defined as one of the below, as determined by the adjudication committee:
- Primary RSV LRTI
- Secondary bacterial LRTI
- Lower respiratory tract infection due to unusual pathogens
- Lower respiratory tract infection, noninfectious or of unknown etiology

Proportion of subjects developing respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) through Day 28

Proportion of all-cause mortality through Day 28

Secondary ID(s)

GS-US-218-0108

2014-002474-36-SE

Source(s) of Monetary Support

Gilead Sciences, Inc.