A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiratory Tract Infections

Intervention / Treatment
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* Biological: Formulation A
* Biological: Formulation B
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Healthy adults who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study. Willing and able to comply with scheduled visits, vaccination plan, laboratory tests, and other study procedures. 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. Sentinel-cohort subjects only: Male and female adults aged 18 to 85 years at the time of enrollment (signing of the ICD). 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: Sentinel-cohort subjects only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality. 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. 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. Participation in other studies involving investigational product within 28 days prior to study entry and/or during study participation. Known infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV). Previous vaccination with any licensed or investigational RSV vaccine, or planned receipt throughout the study of nonstudy RSV vaccine. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product(s). Immunocompromised subjects with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination. 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. 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). Receipt of blood/plasma products or immunoglobulin, from 60 days before investigational product administration or planned receipt throughout the study. 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. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. Women who are pregnant or breastfeeding. Expanded-cohort subjects only: Vaccination with any influenza vaccine within 6 months (182 days) before investigational product administration. Expanded-cohort subjects only: Allergy to egg proteins (egg or egg products) or chicken proteins.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sentinel Arm 1<br>Low dose formulation A | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Sentinel Arm 2<br>Mid dose formulation A | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Sentinel Arm 3<br>High dose formulation A | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Sentinel Arm 4<br>Low dose formulation B | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Sentinel Arm 5<br>Mid dose formulation B | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Sentinel Arm 6<br>High dose formulation B | Biological: Formulation B<br>* RSV vaccine<br>|
| Placebo Comparator: Sentinel Arm 7<br>Placebo | Biological: Placebo<br>* Placebo<br>|
| Experimental: Expanded Arm 8<br>Low dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 9<br>Mid dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 10<br>High dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 11<br>Low dose formulation B and SIIV | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 12<br>Mid dose formulation B and SIIV | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 13<br>High dose formulation B and SIIV | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 14<br>Low dose formulation A and placebo | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 15<br>Mid dose formulation A and placebo | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 16<br>High dose formulation A and placebo | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 17<br>Low dose formulation B and placebo | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 18<br>Mid dose formulation B and placebo | Biological: Formulation B<br>* RSV vaccine<br>|
| Experimental: Expanded Arm 19<br>High dose formulation B and placebo | Biological: Formulation B<br>* RSV vaccine<br>|
| Placebo Comparator: Expanded Arm 20<br>placebo and placebo | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Local Reactions Within 14 Days After Vaccination | Local reactions included pain at injection site, redness and swelling recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: 2.5 to 5.0 cm, moderate: greater than (>) 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. | Within 14 days after vaccination | 
| Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With Local Reactions Within 14 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: interfered with daily activity and severe: prevented daily activity. | Within 14 days after vaccination | 
| Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With Local Reactions Within 14 Days After Vaccination 1 | 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. | Within 14 days after vaccination 1 on Day 1 | 
| Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With Local Reactions Within 14 Days After Vaccination 1 | 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: interfered with daily activity and severe: prevented daily activity. | Within 14 days after vaccination 1 on Day 1 | 
| Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Systemic Reactions Within 14 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. | Within 14 days after vaccination | 
| Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With Systemic Reactions Within 14 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: >= 38.0 deg 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 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. | Within 14 days after vaccination | 
| Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With Systemic Reactions Within 14 Days After Vaccination 1 | 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: >= 38.0 deg 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 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. | Within 14 days after vaccination 1 on Day 1 | 
| Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With Systemic Reactions Within 14 Days After Vaccination 1 | 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: >= 38.0 deg 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 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. | Within 14 days after vaccination 1 on Day 1 | 
| Sentinel Cohort: Percentage of Participants (Aged 18 to 49 Years) With Adverse Events (AEs) Within 1 Month After Vaccination | 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. Serious adverse event (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. | Within 1 month after vaccination (up to 35 days) | 
| Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With AEs Within 1 Month After Vaccination | 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. 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. | Within 1 month after vaccination (up to 35 days) | 
| Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With AE Within 1 Month After Vaccination 1 | 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. 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. | Within 1 month after vaccination 1 (up to 35 days) | 
| Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With AE Within 1 Month After Vaccination | 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. 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. | Within 1 month after vaccination 1 (up to 35 days) | 
| 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 | MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. 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. | Upto 12 months after vaccination (up to 378 days) | 
| Sentinel Cohort: Percentage of Participants (Aged 50 to 85 Years) With MAEs and SAEs Upto 12 Months After Vaccination | MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. 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. | Upto 12 months after vaccination (upto 378 days) | 
| Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With MAEs and SAEs Upto 12 Months After Vaccination 1 | MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. 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. | Upto 12 months after vaccination 1 (upto 378 days) | 
| Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With MAEs and SAEs 12 Months After Vaccination 1 | MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. 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. | Upto 12 months after vaccination 1 (upto 378 days) | 
| Expanded Cohort: Percentage of Participants (Aged 18 to 49 Years) With AEs Within 1 Month After Vaccination 2 | 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. | Within 1 month after vaccination 2 (upto Day 70) | 
| Expanded Cohort: Percentage of Participants (Aged 65 to 85 Years) With AEs Within 1 Month After Vaccination 2 | 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. | Within 1 month after vaccination 2 (upto Day 70) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | GMTs of RSV A and RSV B antigens were measured using neutralizing assay. The neutralizing titer lower limit of quantitation (LLOQ) values were: A = 50 and B = 70. Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. | Before vaccination, and 2 weeks and 1, 2, 3, 6 and 12 months after vaccination | 
| Sentinel Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 50 to 85 Years) | GMTs of RSV A and RSV B antigens were measured using neutralizing assay. The neutralizing titer LLOQ values were: A = 50 and B = 70. Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. | Before vaccination, and 2 weeks and 1, 2, 3, 6 and 12 months after vaccination | 
| Expanded Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 18 to 49 Years) | GMTs of RSV A and RSV B antigens were measured using neutralizing assay. The neutralizing titer LLOQ values were: A = 50 and B = 70. Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. | Before vaccination, 1, 2, 3, 6 and 12 months after vaccination | 
| Expanded Cohort: GMTs of RSV A and RSV B Antigens Following Vaccination in Participants (Aged 65 to 85 Years) | GMTs of RSV A and RSV B antigens were measured using neutralizing assay. The neutralizing titer LLOQ values were: A = 50 and B = 70. Assay results below the LLOQ were set to 0.5*LLOQ. Titers were expressed in terms of 1/dilution. | Before vaccination, 1, 2, 3, 6 and 12 months after vaccination | 
| 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) | The HAI titer LLOQ value for each strain was 10. Assay values below LLOQ were set to 0.5* LLOQ for analysis. Titers were expressed in terms of 1/dilution. | Before vaccination and 1 Month after SIIV vaccination | 
| 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) | The HAI titer LLOQ value for each strain was 10. Assay values below LLOQ were set to 0.5* LLOQ for analysis. Titers were expressed in terms of 1/dilution. | Before vaccination and 1 Month after SIIV vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory tract infections, RSV, vaccine