E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus (RSV) Infection |
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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. |
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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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039247 |
E.1.2 | Term | RSV infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 the study is to evaluate the antiviral effect of GS-5806 in healthy adults infected with RSV-A Memphis 37b (RSV). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the effect of GS-5806 on various viral load-related and symptom-related endpoints, to evaluate the safety and tolerability of GS 5806, and to evaluate the pharmacokinetic (PK) profile of GS-5806 among subjects who have been inoculated with RSV. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Healthy males and females
2. Age 18 to 45 years inclusive
3. Body mass index of 18 to 33 kg/m2 inclusive; total body weight ≥ 50 kg.
4. Agreement to use acceptable contraceptive methods if they are heterosexually active
5. An informed consent document signed and dated by the subject and Investigator
6. Sero-suitable for challenge strain of RSV
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E.4 | Principal exclusion criteria |
1. Presence of any significant acute or chronic, uncontrolled medical illness, that in the view of the Investigator(s), is associated with increased risk of complications of respiratory viral illness
2. Any history during adulthood of asthma, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, reactive airway disease, or any chronic lung condition of any etiology
3. History or evidence of autoimmune disease or known impaired immune responsiveness (of any cause)
4. Confirmed positive human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) test
5. Recent (within the last 3 years of the screening visit) and/or recurrent history of clinically significant autonomic dysfunction (eg, recurrent episodes of fainting, palpitations, etc.)
6. Any significant abnormality altering the anatomy of the nose or nasopharynx
7. Any clinically significant history of epistaxis
8. Any nasal or sinus surgery within 6 months of inoculation
9. Significant history of any tobacco use at any time (≥ total 10 pack year history [eg, 1 pack a day for 10 years])
10. Venous access inadequate for phlebotomy demands of the study
11. Abnormal pulmonary function in the opinion of the Investigator as evidenced by clinically significant abnormalities in spirometry
12. Receipt of any investigational drug within 3 months prior to inoculation, or prior participation in a clinical trial of any RSV IMP, prior participation in a clinical trial using RSV or any other respiratory human viral challenge within 1 year prior to inoculation, or receipt of more than 4 investigational drugs within the previous 12 months
13. Known allergy to components of the Challenge Virus inoculum
14. Symptoms of hay fever on admission into the Quarantine Unit or prior to inoculation
15. Intending to travel within the next 3 months to countries for which vaccinations are recommended
16. Health care workers (including doctors, nurses, medical students and allied healthcare professionals) anticipated to have patient contact within 2 weeks of human viral challenge. Healthcare workers should not work with patients until 14 days after challenge or until their symptoms are fully resolved (whichever is the longer). In particular, any health care workers who work in units housing, elderly, disabled or severely immuno-compromised patients (eg, bone marrow transplant units) will be excluded from participating in the study
17. Those employed or immediate relatives of those employed at RVL or Gilead Sciences
18. Confirmed positive drug screen for class A drugs of abuse or alcohol that cannot be satisfactorily explained (eg, recent use of codeine tablets)
19. Presence of a household member or close contact with someone (for an additional 2 weeks after discharge from the isolation facility) who:
• is less than 3 years of age
• has any known immunodeficiency
• is receiving immunosuppressant medications
• is undergoing or soon to undergo cancer chemotherapy within 28 days of viral inoculation
• has diagnosed emphysema or COPD, is elderly residing in a nursing home, or has severe lung disease or medical condition that may the conditions listed (not exhaustively) in Appendix 2; or
• has received a transplant (bone marrow or solid organ)
20. Any laboratory test or electrocardiogram (ECG) which is abnormal and deemed by the Investigator(s) to be clinically significant
21. Pregnant or nursing, or has a positive pregnancy test at any point in the study, or male subjects whose partners are pregnant
22. Presence of any significant respiratory symptoms existing on the day of inoculation or between admission for quarantine and viral inoculation. History suggestive of respiratory infection within 14 days prior to admission into the Quarantine Unit
23. Acute use (ie, within 7 days prior to human viral challenge) of any medication or other product (prescription or over-the-counter [OTC]), for symptoms of hay fever, rhinitis, nasal congestion, or respiratory tract infection
24. Receipt of systemic glucocorticoids, antiviral drugs, and immunoglobulins (Igs), or any other cytotoxic or immunosuppressive drug within 6 months prior to dosing. Receipt of any systemic chemotherapy agent at any time
25. Receipt of blood or blood products, or loss (including blood donations) of 450 mL or more of blood, during the 3 months prior to inoculation
26. Any other finding in the medical interview, physical exam, or screening investigations that, in the opinion of the Investigator, General Practitioner (GP) or Sponsor deem the subject unsuitable for the study
27. Known allergy to components of the IMP (anhydrous citric acid or mannitol) or apple juice
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the area under the curve (AUC) viral load as measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay from the first viral load measurement post initial dose of investigational medicinal product (IMP) through Day 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Post initial dose of IMP, twice daily (AM and PM), through Day 12 |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are:
• AUC of viral load post challenge through Day 12 as measured by the qRT-PCR assay
• Total weight of mucus produced post initial dose of IMP through last administration of IMP
• AUC of change from baseline of symptoms post initial dose of IMP
Other Endpoints of Interest.
• AUC of viral load from the first viral load measurement post initial dose of IMP through last administration
• Duration of viral shedding from initial dose of IMP to last positive viral load detection (through Day 12)
• Delta peak viral load, as measured by the difference between the viral load on day of peak (for each subject) and the viral load on the 1st detection of viral shedding (for that subject)
• Absolute peak viral load
• Time to peak viral load, as measured from initial dose of IMP
• Time to resolution of viral shedding, as measured from day of peak viral load to last positive virus detection through Day 12
• Total weight of mucus produced post initial dose of IMP through Day 12
• AUC of symptoms after challenge
• AUC of symptoms after challenge until last administration of IMP
• Peak symptoms after challenge
• Peak symptoms post viral inoculation up to last dose of IMP
Viral load endpoints will be analyzed by both qRT-PCR and plaque assay measurement methods. Duration of viral shedding will be analyzed by qRT-PCR and plaque assay.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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LVLS.
Due to the design of the study, (viral challenge study), it may be necessary from a medical safety perspective to follow up any subject beyond the last scheduled visit as a duty of care and in line with International Conference on Harmonisation-E6 (ICH-E6). However, these discretionary follow up visits will not be considered part of the study data (unless this represents follow up and closure on an AE or SAE identified during the study period). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |