E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus (RSV) Infection |
|
E.1.1.1 | Medical condition in easily understood language |
Respiratory Syncytial Virus (RSV) Infection is a respiratory virus that
infects the lungs and breathing passages. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039247 |
E.1.2 | Term | RSV infection |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the effects of
GS-5806 on RSV viral load in RSV-positive adults hospitalized
with acute respiratory infectious symptoms. |
|
E.2.2 | Secondary objectives of the trial |
The effect of GS-5806 on change in the FLU-PRO score
from Baseline
The effect of GS-5806 on the length of hospital stay
The effect of GS-5806 on the rate of unplanned healthcare
encounters (clinic visits, emergency room visits, urgent care
visits, and rehospitalizations) related to a respiratory illness
after discharge
The pharmacokinetics (PK), safety, and tolerability of GS-
5806 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
An informed consent document signed and dated by the subject or a legal guardian of the subject and Investigator or his/her designee
Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 5 of the protocol.
Male subjects must agree to use condoms during heterosexual intercourse and avoid sperm donation while enrolled in the study and for at least 90 days after administration of the last dose of study medication.
All subjects must refrain from blood donation while enrolled in the study and for 30 days after the last dose of IMP.
≥ 18 years of age at Screening
Willing to adhere to protocol specific requirements for contraception
Subject is a current inpatient
New onset or acute worsening of at least 1 upper or lower respiratory infectious symptom ≤ 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
Willingness to perform necessary study procedures and have available a working telephone or email
Documented to be RSV-positive at the current admission within 72 hours of Screening, or as evaluated at Screening |
|
E.4 | Principal exclusion criteria |
Related to concomitant or previous medication use:
- Use of any investigational medicinal product in the 28 days prior to screening, OR use of any investigational monoclonal antibody within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccine ever
- Chronic use (> 28 days of use) of systemic immunosuppressive agents (i.e. alkylating agents, calcineurin inhibitors, immunophilin-binding but not a calcineurin inhibitor, antimetabolites, polyclonal antibodies, monoclonal antibodies) during the 28 days prior to Screening, or anticipated use during the 28 days following Screening
- Use of oral prednisone or other corticosteroid equivalent to:
- >20mg/day for > 14 days prior to screening is not permitted.
- >20mg/day for ≤ 14 days, including corticosteroids received during current hospitalization (ie, bolus doses), is permitted.
- ≤20mg/day, regardless of duration, is permitted.
- Subjects taking a strong CYP inducer including but not limited to rifampin, St John’s wort, carbamazepine, and phenytoin
Related to medical history:
-Pregnant, breastfeeding, or lactating females
-Subjects requiring > 50% supplemental oxygen (while the subject is awake) at Screening
- Subjects with a CFS > 7 at Baseline
- Any clinically significant history of a bleeding disorder (as determined by the
investigator) at any time in the past or epistaxis (as determined by the investigator) within 30 days prior to screening
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
- Known history of HIV/AIDS and a known CD4 count < 200 cells/μl
- 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:
- Influenza-positive as determined by local diagnostic test
- New onset of arrhythmia during current admission
-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
- New cerebrovascular accident or stroke documented at the current admission
- Admission for trauma or emergent or planned surgeries
- Excessive nausea/vomiting at admission, as determined by the investigator, that precludes administration of an orally administered IMP
- Subjects with an unstable medical condition, as determined by the investigator, that preclude participation in the study
Related to allergies:
- Known allergy to components of the IMP (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
Related to laboratory results at Screening:
-Serum creatinine clearance < 40 ml/min
-AST/ALT > 2x ULN
- Total bilirubin > 2x ULN
- Hemoglobin (Hb) < 8 mg/dL
- WBC < 2000 cells/μL
-Neutrophil count < 1500 cells/μL
- Platelet count of < 50,000/μL |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The daily average change in log10 viral load from Baseline (Day 1) to Day 5. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
-Daily average change in the FLU-PRO score from Baseline (Day 1) to Day 5
- Duration of hospital stay following IMP administration
- 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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
New Zealand |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |