The primary objective of this study is to evaluate the effects ofpresatovir (GS-5806) on RSV viral load in RSV-positive adults hospitalizedwith acute respiratory infectious symptoms.The secondary objectives of this study are to evaluate:- The effect…
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Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the time-weighted average change in log10 viral load
from Baseline (Day 1) to Day 5 as measured by qRT-PCR.
Secondary outcome
The key secondary endpoints are:
- Time-weighted average change in the FLU-PRO score from Baseline 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
Additional exploratory endpoints are discussed in Section 3.1.
Pharmacokinetics:
- GS-5806 concentration in plasma at 2 hours +/- 30 minutes following IMP
administration
- GS-5806 concentration in plasma at Days 3 and 5
- The following plasma PK parameters will be calculated for GS-5806 (as
appropriate): Clast, Tlast, and AUClast.
Background summary
RSV infection is a cause of respiratory disease in the adult population.
Respiratory syncytial virus (RSV), a member of the family Paramyxoviridae, is
an enveloped virus with a negative single-strand ribonucleic acid (RNA) genome.
Among adults, the 2 populations that are at higher risk for RSV infection are
the immunocompromised and the elderly. Recently, RSV infection is becoming more
recognized in the elderly population. RSV is responsible for 10.6%, 11.4%,
5.4% and 7.2% of hospitalizations for pneumonia, chronic obstructive pulmonary
disease (COPD), congestive heart failure (CHF), and asthma respectively.
Currently there are no effective approved prophylactic or therapeutic treatment
options for the adult population.
There is a significant unmet medical need for a safe, convenient, and effective
treatment for RSV infection. The only approved antiviral therapy for RSV,
ribavarin, is approved for use in pediatric populations, but is rarely used in
clinical practice due to its limited efficacy and
concerning safety profile. There is no approved antiviral therapy for RSV
infection among adults, where the current standard of care is supportive.
Study objective
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.
The secondary objectives of this study are to evaluate:
- 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
Study design
Randomized, double-blind, placebo-controlled study evaluating the effect of
GS-5806 on RSV viral load, PK, safety, and tolerability in hospitalized adults
with RSV infection.
Intervention
GS-5806 50 mg tablets administered orally
- Dose Day 1 GS-5806: 200 mg (four 50mg tablets)
IMP must be administered after the subject has been fasting for at least 2
hours. The subject will remain in a fasting condition for
approximately 1 hour after dosing.
Study burden and risks
In the study some assessments (such as blood samples, physical exam and urine
collection) are related to this medical scientific research study and are
additional to the treatment patients might have received if they would not
participate in this study.
GS-5806 COMMON ADVERSE EVENTS
Presatovir has been given to almost 340 adults of whom 294 were healthy adult
volunteers. Adults were treated with presatovir for as long as 7 days. No
healthy adult treated with presatovir experienced a serious drug side effect or
a side effect leading to stopping the study.
Adverse events reported by healthy volunteers who received presatovir are
listed below:
Most Observed:
• Bloody nose 8%
• Diarrhea 4%
Less Observed:
• Rash, itchy 3%
• Headache 3%
• Lower value on breathing test 3%
• Constipation 3%
Least Observed:
• Common cold 2%
• Nausea 2%
• Dizziness 2%
• Rash, red 2%
• Stuffy nose 1%
• Sore throat 1%
• Lightheaded 1%
• Back pain 1%
• High liver function test 1%
• Stomach pain 1%
These adverse events were generally mild. Most cases of bloody nose and itchy
rash were due to study related procedures such as nasal swabs and adhesive
tape, and not the study drug.
There is always a l chance that people get an allergic reaction to a drug they
have not taken earlier. Serious allergic reactions that can be life-threatening
may occur. Some things that happen during any allergic reaction to any type of
medication are:
• rash
• having a hard time breathing
• wheezing when you breathe
• sudden drop in blood pressure
• swelling around the mouth, throat, or eyes
• fast pulse
• sweating
Possible Side Effects of Study Procedures
Nasal Swabs: Inserting the swab into the patients nostril may cause
discomfort, irritation, or a tickling sensation in the nostril. It can make
patients cough or make their eyes water. Very rarely, the inside of the nostril
may be irritated by the swab, which may cause slight bleeding. If this happens,
the swab will be taken out right away.
ECGs: Sticky sensors called electrodes will be placed on the chest. After an
ECG, there may be mild irritation, slight redness, and itches at the places on
your skin where the sensors were placed. patients may have to have their chest
shaved for this procedure.
Blood Samples: Drawing blood from a vein may cause local pain, bruising,
occasional light-headedness, fainting, and very rarely, infection at the site
of the blood draw
Urine Test: For females who could become pregnant, providing urine for a
pregnancy test might make them feel embarrassed.
Questionnaires: Patients will fill out a questionnaire and the questions might
make them feel uncomfortable or upset.
The study doctor or other study staff will fill out a health questionnaire and
a health-care assessment form by asking them questions. Answering the questions
might make them feel uncomfortable or upset.
UKNOWN/UNEXPECTED RISKS AND DISCOMFORTS
There may be other risks that do not happen often or that we don*t know about
yet. This could include severe or life-threatening allergic reactions or
interactions with other drugs. Adverse events can sometimes be irreversible or
fatal.
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Seattle WA98102
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Age
Inclusion criteria
1. >= 18 years of age at Screening
2. Willing to adhere to protocol specific requirements for contraception
3. Subject is a current inpatient
4. 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
5. Documented to be RSV-positive as per protocol Section 6.1.1
Exclusion criteria
Related to concomitant or previous medication use:
1. Use of any investigational medicinal products in the 28 days prior to Visit 1, OR use of any investigational monocalonal antibody within 4 months or 5 half-lives of Visit 1 whichever is longer, OR use of any investigational RSV vaccine ever
2. Chronic use (> 28 days of use) of systemic immunosuppressive agents (see Section 4.3) during the 28 days prior to Screening, or anticipated use during the 28 days following Screening
3. 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.
4. 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 condition:
5. Influenza positive as determined by local diagnostic test
6 Known MERS-CoV infection or known coinfection with other coronavirus;7. Subjects requiring > 50% supplemental oxygen (while subject is awake) at Screening
8. Subjects with a Clinical Frailty Score (CFS) > 7 at Baseline
8. Requirement for mechanical ventilation, not including noninvasive ventilation
9. Clinically significant bacteremia or fungemia that has not been adequately treated prior to Screening, as determined by the investigator.
10. Inadequate treatment of confirmed bacterial, fungal, or non- RSV pneumonia, as determined by the investigator
15. Excessive nausea/vomiting at admission, as determined by investigator, that precludes administration of an orally administered Investigational Medicinal Product (IMP)
16. Subjects with an unstable medical condition, as determined by the investigator, that precludes participation in the study;Related to allergies:
* Documented history of acute (anaphylaxis) or delayed (Stevens-Johnson syndrome or epidermal necrolysis) allergy to sulfa drugs
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002137-58-NL |
| ClinicalTrials.gov | NCT02135614 |
| CCMO | NL49680.056.14 |