To evaluate the clinical outcomes, antiviral activity, safety, tolerability, PK, and PK/PD of JNJ 53718678 in adult (ie, adult cohort) and adolescent (ie, adolescent cohort) HSCT recipients with an RSV upper respiratory tract infection (URT)I.The…
ID
Source
Brief title
Condition
- Other condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Health condition
allogene / autologe hematopoietische stamceltransplantaties
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the effect of JNJ 53718678 on the development of RSV lower tract
respiratory infections (LRTIs) in adult hematopoietic stem cell transplant
(HSCT) recipients with RSV upper respiratory tract infection (URTI), as
measured by the proportion of participants who develop RSV LRTI (see definition
below) per the Endpoint Adjudication Committee (EAC)*s assessment through Visit
Day 28.
Secondary outcome
Proportion of Participants who Develop RSV-associated Lower Respiratory Tract
Complication (LRTC)
Number of Participants with Adverse Events (AEs)
Percentage of Participants with Abnormal Clinical Laboratory Findings
Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings
Percentage of Participants with Abnormal Vital Signs Findings
Proportion of Participants Progressing to Respiratory Failure (of any Cause)
Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in
Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC*s
Assessment
Proportion of Participants Progressing to Respiratory Failure (of any Cause)
Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death,
(all-cause Mortality)
Proportion of Participants Progressing to Death (All-cause Mortality), in
Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC*s
Assessment
Proportion of Participants Progressing to Death (All-cause Mortality)
Proportion of Participants Progressing to Respiratory Failure (of any Cause)
Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who
Develop RSV LRTI or RSV-associated LRTC per the EAC*s Assessment
Proportion of Participants Progressing to Respiratory Failure (of any Cause)
Requiring Mechanical Ventilation (Invasive or Noninvasive)
Number of Supplemental Oxygen (O2) Free Days
Incidence of Supplemental Oxygen Requirement
Duration of Supplemental Oxygen
Change from Baseline in Respiratory Rate
Change from Baseline in Heart Rate
Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)
Change from Baseline in Body Temperature
Proportion of Participants Hospitalized (of Participants who Were not
Hospitalized at Baseline)
Proportion of Participants Re-hospitalized
Total Length of Hospital Stay
Total Time in the Intensive Care Unit (ICU)
Incidence of Grade 3 and Grade 4 Adverse Events (AEs)
Incidence of Respiratory AEs
Incidence of Thoracic-related AEs
Incidence of Antibiotic use in Participants who Develop and in Those who do not
Develop RSV LRTI or RSV-Associated LRTC per the EAC*s Assessment
Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity
and Impact Questionnaire (RiiQ) Symptom Scale
Change from Baseline in Severity of Symptoms Reported by Participants in the
RiiQ Symptom Scale Through Day 28
Time to Resolution of Respiratory Illness as Assessed by Patient Global
Impression of Severity (PGI-S) Scale
Change from Baseline in Patient Global Impression of Health (PGI-H) Scale
Through Day 28
Change from Baseline in Patient Global Impression of Change (PGI-C) Scale
Through Day 28
Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours
Postdose (AUC [0-24]) of JNJ-53718678
Trough Plasma Concentration (Ctrough) of JNJ-53718678
Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678
Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral
Activity
Association of Plasma Concentration-time Data of JNJ-53718678 and Safety
Parameters
Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical
Outcomes
RSV Viral Load and Change from Baseline Over Time
RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline)
Time to Undetectable RSV Viral Load
Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint
Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed
by 5-level EuroQol 5-Dimension (EQ-5D-5L) through Day 28
Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through
Day 28
Change from Baseline in the RSV F Gene Sequence
Background summary
RSV is recognized as major respiratory pathogen in infants and young children
and causes upper and lower respiratory illness among all age groups, often
going undiagnosed. Immunocompromised (IC) participants have a reduced ability
to combat infection due to an impaired or weakened immune system. Within the IC
population, HSCT recipients are generally regarded as having a particularly
high risk for more severe disease caused by RSV, representing a substantial
unmet need for antiviral treatment of RSV infections in this participant
population. JNJ-53718678 is an investigational, potent small molecule
respiratory syncytial virus (RSV) specific fusion inhibitor. The study will
include a Screening Period (Day -2 to Day 1), a Treatment Period (Day 1 to Day
21), and a Follow-up Period (1 year). Assessments like chest X-ray, pulse/heart
rate, respiratory rate, electrocardiogram (ECG), etc will be performed. Safety
and efficacy will be assessed through the study. The total study duration for
each participant will be approximately 49 days.
Study objective
To evaluate the clinical outcomes, antiviral activity, safety, tolerability,
PK, and PK/PD of JNJ 53718678 in adult (ie, adult cohort) and adolescent (ie,
adolescent cohort) HSCT recipients with an RSV upper respiratory tract
infection (URT)I.
The primary objective of the study is to evaluate the effect of JNJ-53718678 on
the development of RSV lower tract respiratory infections (LRTIs) in adult
hematopoietic stem cell transplant (HSCT) recipients with RSV upper respiratory
tract infection (URTI).
Study design
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter
study to evaluate the clinical outcomes, antiviral activity, safety,
tolerability, PK, and PK/PD of JNJ 53718678 in adult (ie, adult cohort) and
adolescent (ie, adolescent cohort) HSCT recipients with an RSV URTI.
The study will include a Screening Period (Day -2 to Day 1), a Treatment Period
(Day 1 to Day 21), and a Follow-up Period (1 year). The total study duration
for each participant will be approximately 49 days, after which a long term
follow up period takes place up to 1 year after start of study enrollment.
Intervention
Participants greater than or equal to (>=) 18 to less than or equal to (<=) 75
years of age will receive 250 milligram (mg) JNJ-53718678 twice daily (bid) for
21 days (without coadministration with moderate or strong CYP3A4 inhibitors),
or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong
CYP3A4 inhibitors with the exception of posaconazole), or 125 mg once daily
(qd) for 21 days (when coadministered with posaconazole), or matching placebo
for 21 days.
Study burden and risks
Side effects of standard of care, side effects of study assessments and side
effects/unknown risks associated with the use of JNJ-53718678. throughout
participation in this study. Study enrollments may result in additional
hospital visits in comparison to the stand of care. It is possible that
study-related visit may take longer than usual visits. Subjects are requested
to complete a maximum of 11 study visits during a period of 49 days
(outpatients), which is followed by a long term follow up period until 1 year
after enrollment. A study visit may take approximately 1 - 2 hours, the
screening visits takes approximately 4-5 hours. For patients that are
hospitalized all study procedures are done during admission.
Several measures have been taken to safeguard the safety and health of study
participants throughout the study.
The study will include the following evaluations of safety and tolerability:
- AEs
- clinical laboratory tests (central)
- ECG 12-lead
- vital signs: 1) vital signs assessments performed as part of the clinical
course of RSV infection-related assessments (body temperature, heart rate,
respiratory rate, and SpO2), 2)additional vital signs assessments: systolic
blood pressure (SBP), diastolic blood pressure (DBP)
- physical examination of all body systems (at Screening) (including height and
body weight measurements), direct physical examination, and skin examination
Clinically relevant findings resulting from the physical examination will be
reported as AE. Safety and tolerability will be evaluated throughout the study
from signing of the ICF until the last study related activity.
An Independent Data Monitoring Committee (IDMC) will be established to monitor
and review data in an unblinded manner on a regular basis to ensure the
continuing safety of the participants enrolled in this study. The committee
will meet periodically to review safety data and will meet to review the
results from the interim analysis. After the review, the IDMC will provide
recommendations to the Sponsor Committee, who will be responsible for decision
making, considering the IDMC recommendation, and who will communicate these
decisions to the study team.
An interim analysis will be performed when approximately 50% of the planned
participants in the adult cohort have completed the Day 28 assessments (or
discontinued earlier). This interim analysis will include safety, testing for
futility, early superiority, and a sample size re-estimation.
There are currently no direct-acting antiviral agent approved for prevention or
treatment of RSV infections in HSCT recipients. Since RSV infections in at risk
populations are associated with significant morbidity and mortality, there is a
substantial unmet medical need for effective and safe treatments in HSCT
recipients. This clinical trial will contribute to development of a potential
new treatment to address this unmet medical need and may result in the
registration of JNJ-53718678 as a treatment for RSV infections in an early
stage.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- Male or female
- 18 to 75 years of age, inclusive
- Received an autologous or allogeneic hematopoietic stem cell transplant
(HSCT) using any conditioning regimen
- Absolute lymphocyte count (ALC) less than (<) 1,000 cells/microliter (mL)
- Participant has laboratory confirmed RSV diagnosis within 48 hours of
randomization
- New onset of at least 1 of the following respiratory symptoms within 4 days
prior to the anticipated start of dosing: nasal congestion, rhinorrhea, cough
or pharyngitis (sore throat), and/or worsening of one of these chronic
(associated with previously existing diagnosis, example, chronic rhinorrhea,
seasonal allergies, chronic lung disease) respiratory symptoms within 4 days
prior to the anticipated start of dosing
- Peripheral capillary oxygen saturation (SpO2) greater than or equal to (>=)
92 percent (%) on room air
Exclusion criteria
- Admitted to the hospital primarily for a lower respiratory tract disease of
any cause as determined by the investigator
- Requires supplemental oxygen at Screening or any time between Screening and
randomization
- Documented to be positive for other respiratory viruses (limited to
influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus,
or coronavirus) within 7 days prior to or at the Screening visit, if determined
by local SOC testing (additional testing is not required)
- Clinically significant bacteremia or fungemia within 7 days prior to or at
Screening that has not been adequately treated, 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 | EUCTR2019-001551-39-NL |
| ClinicalTrials.gov | NCT04221412 |
| CCMO | NL71137.056.19 |