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 | 19.0 |
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 presatovir (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 presatovir on change in the FLU-PRO score from Baseline
The effect of presatovir on the length of hospital stay
The effect of presatovir 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 presatovir |
|
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 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
- Willingness to perform necessary study procedures and have available a working telephone or email
- Documented to be RSV-positive as per protocol Section 6.1.1 |
|
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
-Chronic use (> 28 days of use) of oral prednisone equivalent to > 20 mg/day. Chronic prednisone doses equivalent to ≤ 20 mg/day is acceptable. Short courses (≤ 28 days prior to Screening) of oral prednisone equivalent to > 20 mg/day is acceptable if used > 14 days prior to 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 moderate or strong cytochrome P450 (CYP) enzyme 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:
-Pregnant, breastfeeding, or lactating females
- Subjects requiring > 50% supplemental oxygen (while the subject is awake) at Screening
- Subjects with a 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
- Subjects with 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
- Known MERS-CoV infection or known coinfection with other coronavirus
- 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 Sreening, as determined by the investigator.
- Positive bacteremia or fungemia at the current admission
- 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 and 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 time-weighted 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) |
- Time-weighted 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 | 36 |
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 |
Hong Kong |
Israel |
Korea, Republic of |
Netherlands |
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 |