ObjectivesPrimary Efficacy:To demonstrate the efficacy of RSVpreF in preventing LRTI-RSV in the first RSV season following vaccination.Primary Safety:To describe the safety profile of RSVpreF as measured by the percentage of participants reporting…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy:
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
1. VE, defined as the relative risk reduction of first-episode LRTI-RSV cases
with >=2
LRTI signs/symptoms in the RSVpreF group compared to the placebo group in the
first RSV season (starting on Day 15 after study vaccination) and in compliance
with the key protocol criteria (evaluable efficacy population).
2. VE, defined as the relative risk reduction of first-episode LRTI-RSV cases
with >=3 LRTI signs/symptoms in the RSVpreF group compared to the placebo group
in the first RSV season (starting on Day 15 after study vaccination).
Primary Safety:
In participants receiving study intervention:
1. The proportion of participants reporting prompted local reactions within 7
days following study intervention administration in a subset of participants.
2. The proportion of participants. reporting prompted systemic events within 7
days following study intervention administration in a subset of participants.
3. The proportion of participants reporting AEs through 1 month following study
intervention administration.
4. The proportion of participants reporting NDCMCs throughout the study.
5. The proportion of participants reporting SAEs throughout the study.
Secondary outcome
Key Secondary Efficacy:
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
VE, defined as the relative risk reduction of first- episode sLRTI-RSV cases in
the RSVpreF group compared to the placebo group in the first RSV season
(starting on Day 15 after study vaccination).
Secondary Efficacy:
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
- VE, defined as the relative risk reduction of first-episode LRTI-RSV cases
with >=2 LRTI signs/symptoms in the RSVpreF group compared to the placebo group:
• starting on Day 15 after study vaccination through 2 RSV seasons.
• starting on Day 15 after study vaccination through 3 RSV seasons.
VE, defined as the relative risk reduction of first- episode LRTI-RSV cases
with >=3 LRTI signs/symptoms in the RSVpreF group compared to the placebo group
• starting on Day 15 after study vaccination through 2 RSV seasons.
• starting on Day 15 after study vaccination through 3 RSV seasons.
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
• VE, defined as the relative risk reduction of first-episode LRTI-RSV cases
with >=2 LRTI signs/symptoms in the RSVpreF group compared to the placebo group,
in the second RSV season and in the third RSV season.
• VE, defined as the relative risk reduction of first-episode LRTI-RSV cases
with >=3 LRTI signs/symptoms in the RSVpreF group compared to the placebo group,
in the second RSV season and in the third RSV season.
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
- VE, defined as the relative risk reduction of first-episode ARI-RSV cases in
the RSVpreF group compared to the placebo group:
• in the first RSV season (from Day 15), in the second RSV season, and in the
third RSV season.
• starting on Day 15 after study vaccination through the first 2 RSV seasons,
and through all 3 RSV seasons,.
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
- VE, defined as the relative risk reduction of first-episode sLRTI-RSV cases
in the RSVpreF group compared to the placebo group:
• from Day 15 through the 2 RSV seasons.
• starting on Day 15 after study vaccination through 3 RSV seasons.
In participants in compliance with the key protocol criteria (evaluable
efficacy population):
- VE, defined as the relative risk reduction of first- episode sLRTI-RSV cases
in the RSVpreF group compared to the placebo group, in the second RSV season
and in the third RSV season.
Secondary Immunogenicity:
In the immunogenicity subset participants in compliance with the key protocol
criteria (evaluable immunogenicity population):
1. GMT of NT for RSV A and RSV B at each time point after vaccination.
2. GMT of NT for RSV A and RSV B before vaccination.
3. GMFR of NT for RSV A and RSV B from before vaccination to each time point
after vaccination.
4. GMC of RSVpreF-binding IgG at each time point after vaccination.
5. GMC of RSVpreF-binding IgG before vaccination.
6. GMFR of RSVpreF-binding IgG from before vaccination to each time point after
vaccination.
Background summary
RSV is an important cause of severe respiratory disease in older adults and is
associated with a high morbidity and mortality. After RSV natural infection,
immunity is considered to be short-lived. Currently, there is no licensed
vaccine to prevent RSV disease. Current treatments consist primarily of
supportive care. The only available prophylactic measure is an RSV fusion
glycoprotein (F)-specific monoclonal, which is limited to use in high-risk
infants and requires costly, monthly injections. Therefore, there is an
important unmet medical need to develop an effective vaccine to boost the
immune response sufficiently to protect older adults against RSV disease.
The vaccine investigated in this study is a bivalent RSV prefusion F subunit
vaccine (RSVpreF) developed by Pfizer. The RSV F glycoprotein facilitates
fusion of the virion and host cell membrane through a dramatic transition from
an unstable but highly immunogenic prefusion conformation to the more stable
postfusion state. Preclinical studies show that prefusion F elicits much higher
neutralizing antibody titers than postfusion F and that the most potent
neutralizing antibodies from postinfection human sera target the prefusion
form. RSVpreF is composed of engineered, stabilized, trimeric, prefusion F
glycoproteins matching the 2 subgroups (A and B) to help ensure the broadest
coverage against RSV illness.
Study objective
Objectives
Primary Efficacy:
To demonstrate the efficacy of RSVpreF in preventing LRTI-RSV in the first RSV
season following vaccination.
Primary Safety:
To describe the safety profile of RSVpreF as measured by the percentage of
participants reporting local reactions, systemic events, AEs, and SAEs.
Key Secondary Efficacy:
To demonstrate the efficacy of RSVpreF in preventing RSV-associated severe
lower respiratory tract illness (sLRTI-RSV) in the first RSV season following
vaccination.
Secondary Efficacy:
To describe the efficacy of RSVpreF in preventing
- LRTI-RSV across multiple RSV seasons following vaccination
- LRTI-RSV in the second and third RSV seasons
- ARI-RSV at each RSV season and across multiple RSV seasons following
vaccination- sLRTI-RSV across multiple RSV seasons following vaccination
- sLRTI- RSV in the second and third RSV seasons.
Secondary Immunogenicity:
To describe the immune responses induced by RSVpreF following vaccination.
Study design
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled
study to assess the safety, immunogenicity, and efficacy of bivalent RSVpreF in
adults 60 years of age and older.
Intervention
Group 1. The people in this group will get the RSVpreF vaccine.
Group 2. The people in this group will get a placebo.
Study burden and risks
As of June 2021, RSVpreF has been studied in 3 completed and 3 ongoing clinical
trials in healthy adults and pregnant women and was shown to be well tolerated,
with an acceptable safety profile, and highly efficacious in the human
challenge model.
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Age
Inclusion criteria
1. Participants who are willing and able to comply with all scheduled visits,
vaccination plan, laboratory tests, lifestyle considerations, frequent symptom
assessment by mobile device application, and other study procedures, including
collection of nasal swabs by themselves and by study staff when indicated.
2. Healthy participants who are determined by medical history, physical
examination (if required), and clinical judgment of the investigator to be
eligible for inclusion in the study.
Note: Healthy participants with preexisting stable disease, defined as disease
not requiring significant change in therapy or hospitalization for worsening
disease during the 6 weeks before enrollment, can be included. Specific
criteria for participants with known stable infection with HIV, HCV, or HBV can
be found in Section 10.8.
3. Adults who are ambulatory and live in the community, or in assisted-living
or long-term care residential facilities that provide minimal assistance, such
that the participant is primarily responsible for self-care and activities of
daily living.
4. Capable of giving signed informed consent as described in Section 10.1,
which includes compliance with the requirements and restrictions listed in the
ICD and in this protocol.
5. Male or female participants >=60 years of age.
* Male participants able to father children must agree to use a highly
effective method of contraception from the time of informed consent through at
least 28 days after study intervention administration (see Section 10.3.1).
* Female participants must not be of childbearing potential (see Section
10.3.3).
Exclusion criteria
1. Bleeding diathesis or condition associated with prolonged bleeding that
would, in the opinion of the investigator, contraindicate intramuscular
injection.
2. History of severe adverse reaction associated with a vaccine and/or severe
allergic reaction (eg, anaphylaxis) to any component of the study
intervention(s) or any related vaccine.
3. Serious chronic disorder including metastatic malignancy, end-stage renal
disease with or without dialysis, clinically unstable cardiac disease, or any
other disorder that, in the investigator*s opinion, excludes the participant
from participating in the study.
4. Immunocompromised individuals with known or suspected immunodeficiency, as
determined by history and/or laboratory/physical examination.
5. Other medical or psychiatric condition including recent (within the past
year) or active suicidal ideation/behavior or laboratory abnormality that may
increase the risk of study participation or, in the investigator*s judgment,
make the participant inappropriate for the study.
6. Participation in other studies involving study intervention within 28 days
prior to consent and/or through and including the 6-month follow-up visit
(Visit 3). Note: This criterion does not apply to participants who are
participating in a follow-up period for another study involving a study
intervention that is an investigational drug or vaccine, if receipt of the last
dose was at least 12 months prior to consenting for this study and there is no
further dosing anticipated from the previous study during the participant's
participation in this study.
7. Individuals who receive chronic systemic treatment with immunosuppressive
therapy, including cytotoxic agents, monoclonal antibodies, systemic
corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from
60 days before study intervention administration or planned receipt throughout
the study. If systemic corticosteroids have been administered short term (<14
days) for treatment of an acute illness, participants should not be enrolled in
the study until corticosteroid therapy has been discontinued for at least 28
days before study intervention administration. Inhaled/nebulized,
intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are
permitted. Note: Participants with COPD or asthma can be enrolled if chronic
corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.
8. Receipt of blood/plasma products or immunoglobulin within 60 days before
study intervention administration.
9. Previous vaccination with any licensed or investigational RSV vaccine or
planned receipt during study participation.
10. Investigator site staff or Pfizer employees directly involved in the
conduct of the study, site staff otherwise supervised by the investigator, and
their respective family members.
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 | EUCTR2021-003693-31-NL |
| CCMO | NL78577.000.21 |
| Other | US IND number 17931; NCT05035212 |