Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults.

JRCT ID: jRCT2051210096

Registered date:01/10/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Lower Respiratory Tract Illness
• Date of first enrollment: 06/10/2021
• Target sample size: 30000
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Biological: RSVpreF
RSV vaccine (RSVpreF)

Biological: Placebo
Placebo

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Number of first episode of RSV-associated moderate to severe lower respiratory tract illness (msLRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
2.Proportion of participants reporting prompted local reactions within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
Local reactions included pain at injection site, redness and swelling recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm and severe: >10 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfere with daily activity and severe: prevented daily activity
3.Proportion of participants reporting prompted systemic events within 7-days after vaccination [ Time Frame: Within 7 days after vaccination ]
Systemic reactions:fever, fatigue/tiredness, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and any systemic event recorded by participants in an e-diary. Fever: greater than equal to (>=)38.0 degrees (deg) Celsius (C), mild (>=38.0 to 38.4 deg C, >38.4 to 38.9 deg C), moderate (>38.9 to 40.0 deg C and >40.0 deg C), severe (>38.9 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: requires intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h.
4.Proportion of participants reporting AE within 1-month after vaccination [ Time Frame: Within 1 month after vaccination (up to 35 days) ]
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events.
5.Proportion of participants reporting SAE throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
6.Proportion of participants reporting NDCMC throughout the study [ Time Frame: Throughout the study duration (an average of 30 months) ]
An NDCMC is defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects (eg, asthma).

Secondary Outcome

1.Number of first episode of msLRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
2.Number of first episode of msLRTI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
3.Number of first episode of msLRTI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
4.Number of first episode of msLRTI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
1 to 4: Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. msLRTI-RSV is defined as an ARI with 2 or more of the lower respiratory signs/symptoms lasting more than 1 day during the same illness, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
5.Number of first episode of RSV-associated ARI (ARI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
6.Number of first episode of ARI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
7.Number of first episode of ARI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
8.Number of first episode of ARI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
9.Number of first episode of ARI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
5 to 9: Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. ARI-RSV is defined as an ARI with at least 1 signs/symptoms lasting more than 1 day, plus RT-PCR-confirmed RSV infection within 7 days of ARI symptom onset.
10.Number of first episode of RSV-associated severe LRTI (sLRTI-RSV) in the first RSV season [ Time Frame: From Day 15 after vaccination until the end of season 1 visit (an average of 6 months) ]
11.Number of first episode of sLRTI-RSV in the second RSV season [ Time Frame: During the second RSV season (an average of 6 months) ]
12.Number of first episode of sLRTI-RSV in the third RSV season [ Time Frame: During the third RSV season (an average of 6 months) ]
13.Number of first episode of sLRTI-RSV through first 2 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 2 visit (an average of 12 months of surveillance) ]
14.Number of first episode of sLRTI-RSV across 3 RSV seasons [ Time Frame: From Day 15 after vaccination until the end of season 3 visit (an average of 18 months of surveillance) ]
10 to 14: Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)-confirmed RSV A and/or RSV B- associated acute respiratory illness (ARI) is assessed. sLRTI-RSV is defined as msLRTI-RSV with at least 1 of the conditions: 1)Hospitalization due to msLRTI-RSV; 2)New/increased oxygen supplementation; 3)New/increased mechanical ventilation
15.Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B neutralizing titers [ Time Frame: Before vaccination, 1-month after vaccination, before season 2 (approximately 12 months after vaccination), before season 3 (approximately 24 months after vaccination) ]
RSV A and RSV B neutralizing titers (NT), expressed as Geometric Mean Titers (GMTs), and geometric mean fold rise (GMFR). The NTs were calculated as the interpolated reciprocal of the serum dilution resulting in 50% reduction in the number of viral focus forming units when compared to the control without test serum.

16.RSV prefusion-F-binding specific antibody responses (IgG) [ Time Frame: Before vaccination, 1-month after vaccination, before season 2 (approximately 12 months after vaccination), before season 3 (approximately 24 months after vaccination) ]
RSV prefusion-F-binding specific antibody responsee IgG, expressed as Geometric Mean Concentrations (GMCs), and GMFR. The IgG were quantified for RSV A and RSV B separately by incubating test sample sera with streptavidin-coated Luminex.

Key inclusion & exclusion criteria

• Age minimum: >= 60age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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 the protocol.
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 the protocol, 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.
*Female participants must not be of childbearing potential.

Exclude criteria

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 an investigational product within 28 days prior to consent and/or through and including the 6-months 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.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05035212