Clinical trial NCT03572062: A Study to Evaluate the Safety and Immunogenicity of an Adjuvanted RSV Vaccine in Healthy Older 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 AN ADJUVANTED RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN HEALTHY OLDER ADULTS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Tract Infection
Keywords: Respiratory tract infection, RSV, Adjuvant, vaccine
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-06-28
Enrollment: 317
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel
Primary purpose: PREVENTION

Brief summary: The study will evaluate the safety, tolerability, and immunogenicity of up to 7 different RSV vaccine candidates, some with adjuvant, when administered concomitantly with seasonal inactivated influenza vaccine (SIIV) and may evaluate a second dose of RSV vaccine administered12 months after the initial dose.

In addition the study will evaluate a 2-dose regimen administered 2 months apart to 62 subjects.

Detailed description: The study will evaluate the safety, tolerability, and immunogenicity of up to 7 different RSV vaccine candidates, some with adjuvant, when administered concomitantly with SIIV. Healthy male and female subjects between 65 to 85 years of age will be enrolled. Subjects will receive 2 intramuscular injections to assess the concomitant administration of SIIV when given to subjects receiving one of the 3 RSV vaccine dose-level candidates formulated with or without an adjuvant.

If interim support implementation of revaccination, invited, consenting subjects will be revaccinated with the same dose and formulation of the RSV vaccine or placebo received at Visit 1, concomitantly with SIIV. The safety, tolerability, and immunogenicity of the second dose will be evaluated through 12 months after revaccination.

62 subjects will be randomized 1:1 to receive a dose of high dose adjuvanted RSV vaccine or placebo followed by a second dose 2 months later. Safety, tolerability, and immunogenicity will be evaluated. The subjects will be enrolled before the influenza season. There will be no concomitant SIIV administration.

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 and nonchildbearing-potential female adults aged 65 to 85 years at the time of enrollment (signing of the ICD).
5. Subjects must have received the primary vaccination (RSV vaccine or placebo) at Visit 1 and have signed and dated the ICD for participating in the revaccination stage (applies to Primary Study Cohort - Stage 2 subjects).

Exclusion Criteria:

1. 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.
2. Participation in other studies involving investigational product within 28 days prior to study entry and/or during study participation.
3. Known infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
4. Previous vaccination with any licensed or investigational RSV vaccine before enrollment into the study, or planned receipt throughout the study of nonstudy RSV vaccine.
5. Vaccination with any influenza vaccine within 6 months (182 days) before investigational product administration (applies to Primary Study Cohort - Stages 1 and 2).
6. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product(s), including natural rubber latex. In addition, a history of severe allergic reaction (eg, anaphylaxis) to any substance, including documented allergy to egg proteins (egg or egg products) or chicken proteins.
7. Subjects with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
8. 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.Inhaled/nebulized, intra-articular, intrabursal, or topical (epidural, skin or eyes) corticosteroids are permitted.
9. 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 syndrome, idiopathic thrombocytopenic purpura, autoimmune glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).
10. Receipt of blood/plasma products or immunoglobulin, from 60 days before investigational product administration or planned receipt throughout the study.
11. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
12. Female subjects of childbearing potential or who are pregnant or breastfeeding; fertile male subjects who are unwilling to use a highly effective method of contraception for at least 28 days after the last dose of investigational product.
13. 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.
14. Planned donation of blood volumes of approximately 470 mL within 12 weeks after Vaccination 1 (applies to subjects having additional blood drawn for cellular assays).

Primary outcomes:
measure: Primary Cohort: Percentage of Participants With Local Reactions Within 14 Days After Vaccination 1
timeFrame: Within 14 days after Vaccination 1
measure: Primary Cohort: Percentage of Participants With Systemic Events Within 14 Days After Vaccination 1
timeFrame: Within 14 days after Vaccination 1
measure: Primary Cohort: Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination 1
timeFrame: Within 1 month after Vaccination 1
measure: Primary Cohort: Percentage of Participants With Medically Attended Adverse Events (MAEs) and Serious Adverse Events (SAEs) Through 12 Months After Vaccination 1
timeFrame: Up to 12 months after Vaccination 1
Secondary outcomes:
measure: Primary Cohort: Geometric Mean Titers (GMT) of Respiratory Syncytial Virus Subgroup A (RSV A) and Respiratory Syncytial Virus Subgroup B (RSV B) Neutralizing Antibodies Before and 1 Month After Vaccination 1
timeFrame: Before vaccination and 1 Month after Vaccination 1
measure: Primary Cohort: Hemagglutination Inhibition Assay (HAI) and Neutralizing Antibody Geometric Mean Titers for All Strains Following the Seasonal Inactivated Influenza Vaccine (SIIV) Before and 1 Month After Vaccination 1
timeFrame: Before vaccination and 1 Month after Vaccination 1
Other outcomes:
Locations:
city: South Miami
country: United States
facility: Qps Mra, Llc
state: Florida
city: Peoria
country: United States
facility: Optimal Research, LLC
state: Illinois
city: Fremont
country: United States
facility: Synexus Clinical Research US
state: Nebraska
city: Omaha
country: United States
facility: Quality Clinical Research, Inc.
state: Nebraska
city: Maroubra
country: Australia
facility: Australian Clinical Research Network
state: New South Wales
city: Merewether
country: Australia
facility: AIM Centre (Hunter Diabetes Centre)
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital (Infectious Diseases and Microbiology)
state: New South Wales
city: Taringa
country: Australia
facility: Data Health Australia Pty Limited (Trading as AusTrials)
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health
state: Victoria
city: Camberwell
country: Australia
facility: Emeritus Research Pty. Ltd.
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
city: Ivanhoe
country: Australia
facility: Doctors of Ivanhoe
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health
state: Western Australia
city: Spearwood
country: Australia
facility: TrialsWest
state: Western Australia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Baber J, Arya M, Moodley Y, Jaques A, Jiang Q, Swanson KA, Cooper D, Maddur MS, Loschko J, Gurtman A, Jansen KU, Gruber WC, Dormitzer PR, Schmoele-Thoma B. A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults. J Infect Dis. 2022 Dec 13;226(12):2054-2063. doi: 10.1093/infdis/jiac189.