The primary objective of this study is as follows:* To evaluate the effect of presatovir (GS-5806) on nasal RSV viral load in RSV positive LT recipients with acute respiratory symptomsThe secondary objectives of this study are as follows: * To…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The co-primary efficacy endpoints are
* Time-weighted average change in log10 viral load from Day 1/Baseline through
Day 7 (DAVG7) as measured in nasal samples by RT-qPCR among subjects in the FAS
* Time-weighted average change in log10 viral load from Day 1/Baseline through
Day 7 (DAVG7) in a subset of FAS subjects whose duration of RSV symptoms prior
to the first dose of study medication is * median
Secondary outcome
Secondary endpoints are:
* Time-weighted average change in FLU-PRO score from Day 1/Baseline through Day
7
* Percent change from study baseline in FEV1% predicted value at Day 28/End of
Study
Background summary
Randomized, double-blind, placebo-controlled study evaluating the effect of
presatovir on efficacy, PK, safety, and tolerability in LT recipients with RSV
infection.
Study objective
The primary objective of this study is as follows:
* To evaluate the effect of presatovir (GS-5806) on nasal RSV viral load in RSV
positive LT recipients with acute respiratory symptoms
The secondary objectives of this study are as follows:
* To evaluate the effect of presatovir on clinical sequelae of RSV infection
and on measures of lung function
* To evaluate the pharmacokinetics (PK), safety, and tolerability of presatovir
Study design
All subjects will be permitted to receive the standard-of-care therapy for RSV
infection per their local medical practices, in addition to the investigational
medicinal product (IMP).
Subjects will be randomized in a 2:1 ratio to receive presatovir administered
as a 200-mg dose on Day 1/Baseline, followed by a 100 mg dose daily on Days 2
through 14, or placebo-to-match (PTM) once daily for a total of 14 days. All
subjects will be stratified by 2 factors:
* Treatment of RSV infection (yes or no) with ribavirin (oral, intravenous, or
aerosolized)
* Use of palivizumab or IVIG (yes or no)
At time of informed consent, subjects will be presented with the options to:
* Participate in optional DNA sampling for potential pharmacogenetic studies
* Participate in optional extended viral monitoring involving weekly nasal
sampling for an additional 28 days after Day 28/End of Study (to Day 56). This
sampling will be used to assess the duration of viral shedding and occurs only
if the Day 21 nasal sample is PCR-positive or inconclusive for RSV.
* Participate in optional nasal sampling for gene expression analyses on Days
1/Baseline, 5, 7, and 21
* Participate in optional 48-week data registry involving collection of
long-term clinical data to explore potential associations between RSV infection
(and treatment) and the onset of lung transplant complications
Intervention
Subjects will be randomized in a 2:1 ratio to receive presatovir administered
as a 200-mg dose on Day 1/Baseline, followed by a 100 mg dose daily on Days 2
through 14, or placebo-to-match (PTM) once daily for a total of 14 days.
Study burden and risks
Burden:
- Blood sampling: 6x
- Questions and questionnaires: every visit
- Nasale sample: every visit
- PK sample: 4x
- ECG: 2 or 3x
- saturation: 9x
- spirometry: 9x
There are risks involved with taking presatovir.
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. Most and less observed side
effects reported by any presatovir healthy volunteer are listed below.
Most Observed
* Bloody nose 8%
* Diarrhea 4%
Less Observed
* Rash (itching) 3%
* Headache 3%
* Lower value on breathing test 3%
* Constipation 3%
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.
Flowers Building, Granta Park, Abington -
Cambridge CB21 6GT
GB
Flowers Building, Granta Park, Abington -
Cambridge CB21 6GT
GB
Listed location countries
Age
Inclusion criteria
1) Males and females * 18 years of age who have received a LT (single or double) or heart/lung
transplant > 90 days prior to Screening
2) Confirmed to be RSV-positive by local polymerase chain reaction (PCR) testing (starting
from when the upper or lower respiratory tract sample is obtained) * 7 days prior to IMP
administration on Day 1/Baseline
3) New onset or acute worsening, if the symptom is chronic, of at least 1 of the following
respiratory symptoms * 7 days prior to IMP administration on Day 1/Baseline: nasal
congestion, earache, runny nose, cough, sore throat, shortness of breath, or wheezing
4) An informed consent document signed and dated by the subject
5) A negative local urine or serum pregnancy test for female subjects of childbearing potential
at Screening within 1 day prior to IMP administration. When available, existing local
pregnancy test results obtained prior to Screening may be used, provided the testing was
completed within 1 day prior to IMP administration.
6) Agreement from male and female subjects of childbearing potential who engage in
heterosexual intercourse to use protocol specified method(s) of contraception as described in
Appendix 6
7) Ability and willingness to complete necessary study procedures
Exclusion criteria
1) Use of any 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 prior investigational RSV vaccines
2) Use of a strong or moderate 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
3) Use of any of the following lympholytic treatment within the stated time frame:
anti-thymocyte globulin (ATG), < 3 months; anti-lymphoblast globulin (ALG), < 3 months;
muromonab-CD3 (OKT3), < 3 months; rituximab < 6 months; alemtuzumab < 9 months
Related to transplant history:
4) Recipient of any other organ transplant prior to Screening, with the exception of a LT
(single or double) or heart/lung transplant
5) Recipient of a hematopoietic cell transplant at any time
6) Presence of BOS Stage 3 at Screening defined as a FEV1 of 50% or less of baseline
Related to medical condition at Screening:
7) Respiratory failure requiring invasive mechanical ventilation
8) Evidence of shock requiring vasopressors
9) Known viral coinfection (including but not limited to influenza, metapneumovirus, human
rhinovirus, parainfluenza, cytomegalovirus, or coronavirus) in the upper or lower respiratory
tract * 14 days prior to Screening unless discussed with the medical monitor and deemed
acceptable
10) Active systemic infection or infectious pneumonia of any etiology (ie, bacterial, viral
[other than RSV] or fungal), including aspiration pneumonia, that is considered clinically
significant by the investigator unless discussed with the medical monitor and deemed
acceptable
11) Pregnant or lactating females
12) Evidence of recent and rapidly deteriorating lung function, occurring before the onset of the
current viral respiratory infection, including but not limited to: acute lung allograft rejection,
rapidly-progressive CLAD, and rCLAD (as determined by the investigator)
13) Any condition which, in the opinion of the investigator, would prevent full participation in
this study or would interfere with the evaluation of the trial endpoints
Related to allergies:
14) 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)
15) History of hypersensitivity, anaphylactic reaction, Stevens-Johnson Syndrome, or toxic
epidermal necroylsis response to sulfa drugs
Related to laboratory values:
16) Clinically significant kidney dysfunction as defined by:
An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as calculated by the
Modification of Diet in Renal Disease (MDRD) study 4 parameter equation obtained from
screening laboratory measurements or via local laboratory measurements obtained * 7 days
prior to Screening. The eGFR may be manually calculated or the reported eGFR value may
be used, but any automatically calculated eGFR must be calculated using the MDRD
equation.
17) Clinically significant liver function test abnormalities as defined by an ALT or AST
> 5 times the ULN obtained in screening laboratory measurements or via local laboratory
measurements obtained * 7 days prior to Screening
18) Clinically significant elevations in total bilirubin (TB), as determined by the investigator
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 | EUCTR2015-002287-16-NL |
CCMO | NL59391.078.16 |