Study A: Validation of productive infection of RSV CHIMStudy B: Effectiveness and immunogenicity of local administration of palivizumab on prevention of experimental RSV infection
ID
Source
Brief title
Condition
- Viral infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study A:
1. Productive infection (defined as 2 positive viral detections by PCR assay on
2 consecutive sampling points during the quarantine, post RSV inoculation).
Study B will start if there is productive infection in 1/6 volunteers in Study
A and there are no serious adverse events related to viral inoculation. See
detailed protocol for transition to Study B if these criteria are not met.
Study B:
1. Area under the curve (AUC) for viral load as determined by quantitative PCR
from a daily nasal-wash sample from day 2 to day 14 similar to previous studies
(Devincenzo NEJM 2014, Devincenzo NEJM 2015).
Secondary outcome
Study A: Safety measured by self-reported and physician-reported local and
systemic adverse events; transmission of RSV to healthcare workers and fomites
Study B: Safety, pharmacokinetics, lung function over time, anti-drug
antibodies, immunologic endpoints (cytokines and leukocytes)
Background summary
Globally respiratory syncytial virus (RSV) is the second cause of death after
malaria in infants. RSV immunoprophylaxis with palivizumab is prohibitively
expensive and only administered to high risk children in developed countries.
There is a need to make palivizumab affordable through local administration. We
established preclinical proof of concept in mice: intranasal (IN) palivizumab
provides full protection against RSV for at least a week after administration.
We tested the stability and shelf-life of a of palivizumab in nose drop
formulation. In a phase I double-blind RCT we showed safety in healthy adult
volunteers. This study will provide clinical proof of concept that IN
administration will block RSV at the point of entry (Bouncer Hypothesis) in
experimental human infection. To mitigate the risks of large and costly
late-stage trials, an RSV controlled human infection model (CHIM) allows for a
rapid proof of concept that is also cost-effective to test for efficacy of the
proposed IN administration at an earlier stage. The World Health Organization
(WHO) has determined that CHIM contributes vital scientific knowledge and can
significantly accelerate clinical development.
Study objective
Study A: Validation of productive infection of RSV CHIM
Study B: Effectiveness and immunogenicity of local administration of
palivizumab on prevention of experimental RSV infection
Study design
Study A: Validation of RSV CHIM in healthy adult volunteers: Productive
infection in RSV CHIM; If there are 1/6 productive infections, then study B
will start
Study B: Phase II RCT: Non-therapeutic double-blind placebo-controlled
proof-of-concept trial of RSV prevention through IN administration of
palivizumab or placebo in healthy adult volunteers
Intervention
Study A: No intervention, only viral challenge.
Study B: 0,1mL nose drops per nostril (1mg/mL palivizumab or placebo)
administered one time each as a prophylaxis 2 hours before the viral challenge
Study burden and risks
This is a validation study. There are two main risks of CHIM that should be
considered (1) risk of severe infection in study subjects and (2) risk of
transmission from experimentally-infected individuals to researchers or the
broader public. Healthy young adults do not suffer from severe RSV infection,
but at most develop mild-to-moderate common cold symptoms after experimental
RSV infection. RSV CHIM has been used safely in clinical trial settings to test
antivirals. The potential risk of transmission of RSV from
experimentally-infected individuals to research staff and the wider public will
be addressed using infection control standard procedures and will be monitored.
These SOP*s will be developed and designed with the support of the Department
of Infection Control at UMCU (Dr. Annet Troelstra and Dr. Herman Wunderink).
The burden of the study includes 10 days of inpatient quarantine as well as
minimally invasive study procedures including viral inoculation, daily nasal
sampling (nasal lavage, scrape, nasopharyngeal swabs). There is no direct
benefit to patients who participate in the study. Study B: This is a
non-therapeutic study. The safety risks of CHIM are mitigated by evaluation of
Study A to continue to Study B. The main difference is that Study B will occur
in the outpatient setting. Measures will be taken to understand and carefully
limit transmission risk in Study A. Furthermore, volunteers will undergo
self-quarantine for a period of 10 days, be trained in transmission prevention
measures as outlined above in the protocol, and will be screened for children
<3 years of age in the household to limit transmission of RSV. Minimal risk is
associated with the IMP which have been previously evaluated by the Ethics
Committee in the Narsyn trial. Additional safety data has been collected in the
phase I and IIB trial. Risks are described in more detail in section 10.4. We
have shown the intranasal formulation to be safe in a phase I trial in healthy
adults. The burden of the study includes 10 days of self-quarantine. Study
procedures are non-invasive (nasal washes, nasosorption, lung function
measurements, nasal scrapes) except for 10 blood draws. There is no direct
benefit to patients who participate in the study.
POB 85090 Kamer E4.133.1
Utrecht 3508 AB
NL
POB 85090 Kamer E4.133.1
Utrecht 3508 AB
NL
Listed location countries
Age
Inclusion criteria
1. Healthy males or females
2. Age 18-55 years
3. Signed and dated informed consent form
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study: 1. Child younger than 3 years old living in
subject*s household 2. Person older than 65 years old or significant primary or
secondary immunodeficiency living in subjects household 3. Presence of
significant acute or chronic medical illness that is associated with increased
risk of respiratory viral illness related complications. These include but are
not limited to: a. Recent (within adulthood) history of asthma, COPD,
hypertension, reactive airway disease, or any other chronic lung illness b.
History or evidence of impaired immune responsivity or autoimmune disease c.
Confirmed hepatitis B (HBV), human immunodeficiency virus (HIV), or hepatitis C
(HCV) test 4. Adults with a nasal cold or obstructions which could interfere
with administration of the study intervention 5. Simultaneous use of other
nasal drops, sprays, or medications 6. Nasal surgery prior to or during the
trial 7. Positive COVID-test 48 hours prior to start of the study 8. Pregnancy
9. Symptoms of clear nasal congestion
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 | EUCTR2020-004137-21-NL |
| CCMO | NL78591.041.21 |