Clinical trial NCT03529773: A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults
Official title: A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING, FIRST-IN-HUMAN STUDY TO DESCRIBE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN HEALTHY ADULTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Tract Infections
Keywords: Respiratory tract infections, RSV, vaccine
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-05-18
Enrollment: 1235
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel
Primary purpose: PREVENTION

Brief summary: The study will describe the safety, tolerability, and immunogenicity of up to 6 RSV vaccine formulations when administered alone or concomitantly with seasonal inactivated influenza vaccine (SIIV).

Detailed description: The study will describe the safety, tolerability, and immunogenicity of up to 6 RSV vaccine formulations when administered alone or concomitantly with SIIV. Healthy male and female subjects divided into 2 age groups (18-49 years of age and 50-85 years of age in the sentinel cohort and 18-49 years of age and 65-85 years of age in the expanded cohort) will be enrolled. Age groups will run in parallel. Subjects in the sentinel cohort in each age group will receive one of two RSV vaccine formulations at one of 3 antigen dose levels or placebo. Subjects in the expanded cohort in each age group will receive one of two RSV vaccine formulations at one of 3 antigen dose levels with and without SIIV.

Eligibility criteria: Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject has been informed of all pertinent aspects of the study.
2. Healthy adults who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.
3. Willing and able to comply with scheduled visits, vaccination plan, laboratory tests, and other study procedures.
4. Male subject who is able to father children and willing to use a highly effective method of contraception as outlined in this protocol until at least 28 days after the last dose of investigational product; female subject who is of childbearing potential and at risk for pregnancy and who is willing to use a highly effective method of contraception as outlined in this protocol until at least 28 days after the last dose of investigational product; male subject not able to father children; female subject not of childbearing potential.
5. Sentinel-cohort subjects only: Male and female adults aged 18 to 85 years at the time of enrollment (signing of the ICD).
6. Expanded-cohort subjects only: Male and female adults aged 18 to 49 years of age or 65 to 85 years at the time of enrollment (signing of the ICD).

Exclusion Criteria:

1. Sentinel-cohort subjects only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
2. Sentinel-cohort subjects only: Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (HBc Abs), or hepatitis C virus antibodies (HCV Abs) at the screening visit.
3. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
4. Participation in other studies involving investigational product within 28 days prior to study entry and/or during study participation.
5. Known infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
6. Previous vaccination with any licensed or investigational RSV vaccine, or planned receipt throughout the study of nonstudy RSV vaccine.
7. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product(s).
8. Immunocompromised subjects with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
9. Subjects who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (\<14 days) for treatment of an acute illness, subjects should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before investigational product administration. Intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
10. Subject with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).
11. Receipt of blood/plasma products or immunoglobulin, from 60 days before investigational product administration or planned receipt throughout the study.
12. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
13. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
14. Women who are pregnant or breastfeeding.
15. Expanded-cohort subjects only: Vaccination with any influenza vaccine within 6 months (182 days) before investigational product administration.
16. Expanded-cohort subjects only: Allergy to egg proteins (egg or egg products) or chicken proteins.

Primary outcomes:
measure: Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Local Reactions Within 14 Days After Vaccination
timeFrame: Within 14 days after vaccination
measure: Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With Local Reactions Within 14 Days After Vaccination
timeFrame: Within 14 days after vaccination
measure: Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With Local Reactions Within 14 Days After Vaccination 1
timeFrame: Within 14 days after vaccination 1 on Day 1
measure: Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With Local Reactions Within 14 Days After Vaccination 1
timeFrame: Within 14 days after vaccination 1 on Day 1
measure: Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Systemic Reactions Within 14 Days After Vaccination
timeFrame: Within 14 days after vaccination
measure: Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With Systemic Reactions Within 14 Days After Vaccination
timeFrame: Within 14 days after vaccination
measure: Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With Systemic Reactions Within 14 Days After Vaccination 1
timeFrame: Within 14 days after vaccination 1 on Day 1
measure: Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With Systemic Reactions Within 14 Days After Vaccination 1
timeFrame: Within 14 days after vaccination 1 on Day 1
measure: Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Adverse Events (AEs) Within 1 Month After Vaccination
timeFrame: Within 1 month after vaccination (up to 35 days)
measure: Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With AEs Within 1 Month After Vaccination
timeFrame: Within 1 month after vaccination (up to 35 days)
measure: Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With AE Within 1 Month After Vaccination 1
timeFrame: Within 1 month after vaccination 1 (up to 35 days)
measure: Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With AE Within 1 Month After Vaccination
timeFrame: Within 1 month after vaccination 1 (up to 35 days)
measure: Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Medically Attended Adverse Events (MAEs) and Serious Adverse Events (SAEs) Upto 12 Months After Vaccination
timeFrame: Upto 12 months after vaccination (up to 378 days)
measure: Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With MAEs and SAEs Upto 12 Months After Vaccination
timeFrame: Upto 12 months after vaccination (upto 378 days)
measure: Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With MAEs and SAEs Upto 12 Months After Vaccination 1
timeFrame: Upto 12 months after vaccination 1 (upto 378 days)
measure: Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With MAEs and SAEs 12 Months After Vaccination 1
timeFrame: Upto 12 months after vaccination 1 (upto 378 days)
measure: Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With AEs Within 1 Month After Vaccination 2
timeFrame: Within 1 month after vaccination 2 (upto Day 70)
measure: Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With AEs Within 1 Month After Vaccination 2
timeFrame: Within 1 month after vaccination 2 (upto Day 70)
Secondary outcomes:
measure: Sentinel Cohort: Geometric Mean Titers (GMTs) of Respiratory Syncytial Virus Subgroup A (RSV A) and RSV B Antigens Following Vaccination in Participants (Aged 18 to 49 Years)
timeFrame: Before vaccination, and 2 weeks and 1, 2, 3, 6 and 12 months after vaccination
measure: Sentinel Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 50 to 85 Years)
timeFrame: Before vaccination, and 2 weeks and 1, 2, 3, 6 and 12 months after vaccination
measure: Expanded Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 18 to 49 Years)
timeFrame: Before vaccination, 1, 2, 3, 6 and 12 months after vaccination
measure: Expanded Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 65 to 85 Years)
timeFrame: Before vaccination, 1, 2, 3, 6 and 12 months after vaccination
measure: Expanded Cohort: Hemagglutination Inhibition Assay (HAI) Titers for All Strains Following Vaccination With Seasonal Inactivated Influenza (SIIV) Vaccine in Participants (Aged 18 to 49 Years)
timeFrame: Before vaccination and 1 Month after SIIV vaccination
measure: Expanded Cohort: Hemagglutination Inhibition Assay (HAI) Titers for All Strains Following Vaccination With Seasonal Inactivated Influenza (SIIV) Vaccine in Participants (Aged 65 to 85 Years)
timeFrame: Before vaccination and 1 Month after SIIV vaccination
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Anaheim
country: United States
facility: Anaheim Clinical Trials
state: California
city: La Mesa
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Center
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Sioux City
country: United States
facility: Meridian Clinical Research Dakota Dunes
state: Iowa
city: Augusta
country: United States
facility: Augusta Family Practice
state: Kansas
city: Augusta
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Newton
country: United States
facility: Axtell Clinic, P.A.
state: Kansas
city: Newton
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Binghamton
country: United States
facility: United Medical Associates
state: New York
city: Endwell
country: United States
facility: Regional Clinical Research, Inc.
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health/Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte, LLC
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Fort Worth
country: United States
facility: Texas Health Care, PLLC
state: Texas
city: Fort Worth
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research
state: Texas
city: Fort Worth
country: United States
facility: HealthFirst Medical Group
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. /Foothill Family Clinic South
state: Utah
city: South Jordan
country: United States
facility: J.Lewis Research, Inc. / Jordan River Family Medicine
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Walsh EE, Falsey AR, Scott DA, Gurtman A, Zareba AM, Jansen KU, Gruber WC, Dormitzer PR, Swanson KA, Radley D, Gomme E, Cooper D, Schmoele-Thoma B. A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine. J Infect Dis. 2022 Apr 19;225(8):1357-1366. doi: 10.1093/infdis/jiab612.
citation: Falsey AR, Walsh EE, Scott DA, Gurtman A, Zareba A, Jansen KU, Gruber WC, Dormitzer PR, Swanson KA, Jiang Q, Gomme E, Cooper D, Schmoele-Thoma B. Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Syncytial Virus Prefusion F Vaccine in Adults With Concomitant Inactivated Influenza Vaccine. J Infect Dis. 2022 Jun 15;225(12):2056-2066. doi: 10.1093/infdis/jiab611.