Primary ObjectivesThe primary objectives are to evaluate in infants who are hospitalized with RSV infection:• the pharmacokinetics of JNJ-53718678 after multiple oral doses;• the safety and tolerability of JNJ-53718678 when administered for 7 days.…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints are:
• the pharmacokinetic parameters of JNJ-53718678;
• the safety/tolerability data including, but not limited to, AEs, physical
examinations, vital
signs, ECGs, and clinical laboratory results.
Secondary outcome
The secondary endpoints are:
• RSV viral load as measured by qRT-PCR in nasal swabs will be used to
determine the following;
-AUC of RSV viral load over time;
-viral load over time, peak viral load, and time to peak viral load;
-proportion of subjects reaching undetectability of virus between first
administration of study drug and Day 28.
•RSV clinical course endpoints including:
-Length of hospital stay from admission to discharge;
-Need and duration of supplemental oxygen requirement (type and duration [h]);
-Need and duration of ICU stay;
-Need and duration of non-invasive ventilator support (eg, continuous positive
airway
pressure [CPAP]);
-Number of hours until saturation >92% on room air;
-Need and duration of endotracheal mechanical ventilation;
-Evolution of respiratory rate, SpO2, and body temperature;
-Evolution of RSV symptoms as assessed by the clinician COA;
-Amount of food intake, hydration, and feeding by IV.
Exploratory endpoints are:
• Evolution of RSV symptoms as assessed by the parent/caregiver COA;
• Relationship between various pharmacokinetic parameters and RSV clinical
course and
antiviral endpoints;
• Impact of viral genotype on antiviral response;
• Sequence analysis of the RSV F-gene before treatment (at baseline), during
treatment, and
post-treatment, as applicable;
• Presence of co-infections at Screening and detected retrospectively. The
methodology that
will be used to detect co-infections will be described in a separate
laboratory manual;
• Time to clinical stability.
Background summary
RSV is considered the most important virus causing acute lower respiratory
tract infection (LRTI) and is a major cause of hospital admissions and death in
young children worldwide. Infants that are born prematurely or close to the RSV
season and/or suffering from bronchopulmonary dysplasia or congenital heart
disease are at the highest risk of developing severe RSV-related acute LRTI. In
addition, RSV infection results in substantial illness and morbidity in the
elderly and adults with underlying chronic illnesses, underlying disorders of
cellular immunity, or suppressed immune systems.
Despite the large medical and economic burden, treatment options for
RSV-associated bronchiolitis and pneumonia are limited: prophylactic treatment
with passive immunization with the humanized monoclonal antibody palivizumab,
treatment with ribavirin, and supportive treatment such as oxygenation and
mechanical ventilation are available. There is an unmet medical need for
prophylactic (pre- and post-exposure) as well as therapeutic treatment in both
children and adults.
Study objective
Primary Objectives
The primary objectives are to evaluate in infants who are hospitalized with RSV
infection:
• the pharmacokinetics of JNJ-53718678 after multiple oral doses;
• the safety and tolerability of JNJ-53718678 when administered for 7 days.
Secondary Objectives
The secondary objectives are to evaluate in infants who are hospitalized with
RSV infection:
• the impact of JNJ-53718678 when administered for 7 days on the clinical
course of RSV
infection, as assessed by the clinician;
• the antiviral activity of JNJ-53718678 when administered for 7 days.
Exploratory Objectives
The exploratory objectives are to assess in infants who are hospitalized with
RSV infection:
• the relationship between the pharmacokinetics and the pharmacodynamics after
repeated
oral dosing of JNJ-53718678 for 7 days;
• the evolution of viral resistance under JNJ-53718678 treatment;
• the impact of the viral genotype on the antiviral response;
• the impact of JNJ-53718678 when administered for 7 days on the clinical
course of RSV
during and following hospitalization as assessed by the subject*s
parent(s)/caregiver(s) in the
electronic clinical outcome assessments (COAs) through end of
follow-up.
Study design
This is a Phase 1b, double-blind and placebo-controlled (except for the 1st
cohort within each age group which is open-label), randomized, multicenter,
multiple ascending dose study in infants who are hospitalized with RSV
infection.
Intervention
Subjects will be dosed orally once daily (qd) or twice daily (bid), depending
on the assigned dose regimen, during 7 days (Day 1-Day 7). Dosing should occur
approximately at the same time(s) each day.
Each cohort in Part 1 will consist of 5 subjects (4 subjects receiving
JNJ-53718678 and 1 subject receiving placebo), except for the first cohort of
each age group which will contain only 4 subjects (4 subjects receiving
JNJ-53718678). As such, each age group will include a minimum of 12 and a
maximum of 20 subjects who will receive JNJ-53718678 treatment, and a minimum
of 2 and a maximum of 4 subjects who will receive placebo, depending on the
number of cohorts per age group.
Recruitment for Cohort f (Part 2 of the study) can start for a particular age
group as soon as the last cohort of Part 1 for that respective age group has
been completed through Day 7 and the safety/tolerability data and full
pharmacokinetic data for the selected dose regimen has been reviewed and the
DRC recommended the start of Cohort f for that respective age group. Dose
and/or dosing regimen will be adapted or determined, as applicable, based on
the review of the safety/tolerability and pharmacokinetic data integrating all
data available at the time of the data review (completed and ongoing age
groups/cohorts).
Study burden and risks
The subjects receive JNJ-53718678 during 7 days. Furthermore, nasal swabs and
blood (max 5 times) will be taken from the subjects. The subjects will be in
the hospital for two nights and visits will take place on day 7, 14 and 28
(will take 2 hours).
A recent study shows that children who are hospitalized, almost always are
hospitalized at least 2 nights and often longer. So there is no additional
burden on the hospitalization.
The total blood volume to be collected is considered to be in line with
generally acceptable guidelines for the collection of blood samples for these
age groups.11 For each pharmacokinetic sample 30 microliter of blood is
required. The amount of blood for the safety samples will depend on
local practice (eg, heel or finger prick versus venous sample), however sites
are encouraged to limit the volume as much as possible.
The maximum amount of blood drawn from each subject for study-specific purposes
will not exceed 3 mL/kg body weight over the duration of the study.
The other sampling (nasal swab) is kept as minimal as possible in order to keep
the burden as low as possible.
No specific safety concerns were identified based on the currently available
clinical data.
Eastgate Village, Little Island, CO Cork 1
Cork 0000 Eastgate
IE
Eastgate Village, Little Island, CO Cork 1
Cork 0000 Eastgate
IE
Listed location countries
Age
Inclusion criteria
1. Each subject*s legally acceptable representative (ie, parent(s)/legal guardian/caregiver) must sign an ICF indicating that he or she understands the purpose of and procedures required for the study, are willing for their child to participate in the study, are willing for their child to remain in the hospital for the first 3 days of dosing (even if not clinically indicated), and are willing/able to adhere to the prohibitions and restrictions specified in the protocol (see Section 4.3) and study procedures.
2. Subject has presented at the hospital for suspected RSV infection within 72 hours prior to screening completion (ie, randomization).
3. Subject has been hospitalized for this suspected RSV infection.
4. Subject is a boy or a girl, who is >1 month to <=24 months of age on the day of randomization.
5. Subject has been diagnosed with RSV infection using a polymerase chain reaction (PCR)-based assay, preferably commercially available locally.
Note: in case there is no commercially available PCR-based assay at the site, the
Sponsor should be consulted for agreement on the assay to be used.
6. Subject was born after a normal term pregnancy (>=37 weeks and 0 days).
7. With the exception of the RSV-related illness, subject is otherwise in good health without any significant medical illness on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination, skin examination, medical history, vital signs, ECG, and the results of blood biochemistry, blood coagulation, and hematology tests performed at Screening. If there are abnormalities, the subject may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject*s source documents and initiated by the Investigator.
Note: Procedures that are standard of care and performed within 72 hours prior to screening completion (ie, randomization) may be used in determining study eligibility.
Exclusion criteria
1. Subject is upon current admission initially hospitalized in the ICU and/or in need of invasive endotracheal mechanical ventilation.
2. Subject has a history of any illness or a concurrent illness that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject or that could prevent, limit or confound the protocol-specified assessments. This may include, but is not limited to, bacteremia, gross abnormalities, organ dysfunction, or severe comorbidity.
Note: The use of intravenous fluids is not exclusionary as long as the Investigator believes the patient*s gastrointestinal tract still functions properly (i.e., is able to absorb drugs or nutrition).
3. Subjects who had major surgery within the 28 days prior to randomization or planned major surgery through the course of the study.
4. Subject has major congenital anomalies (eg, AV shunt) or known cytogenetic disorders (eg, Down*s syndrome).
Note: Open ductus arteriosus and open foramen ovale are not exclusionary as not considered major anomalies.
5. Subject has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection.
6. Subject has known or suspected hepatitis B or C infection.
7. Subject has known allergies, hypersensitivity, or intolerance to JNJ-53718678 or its excipients.
Design
Recruitment
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 | EUCTR2015-002003-28-NL |
| ClinicalTrials.gov | NCT02593851 |
| CCMO | NL57881.000.16 |