A Study to Evaluate the Safety and Immunogenicity of an Adjuvanted RSV Vaccine in Healthy Older Adults

Study Overview
=================
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.

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

Conditions
-----------------
Respiratory Tract Infection

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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 and nonchildbearing-potential female adults aged 65 to 85 years at the time of enrollment (signing of the ICD). 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: 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 before enrollment into the study, or planned receipt throughout the study of nonstudy RSV vaccine. Vaccination with any influenza vaccine within 6 months (182 days) before investigational product administration (applies to Primary Study Cohort - Stages 1 and 2). 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. 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.Inhaled/nebulized, intra-articular, intrabursal, or topical (epidural, 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 syndrome, idiopathic thrombocytopenic purpura, autoimmune 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. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. 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. 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. 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).

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: Arm 1<br>Low dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Arm 2<br>Low dose formulation B and SIIV | Biological: Formulation B<br>* Adjuvanted RSV vaccine<br>|
| Experimental: Arm 3<br>Mid dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Arm 4<br>Mid dose formulation B and SIIV | Biological: Formulation B<br>* Adjuvanted RSV vaccine<br>|
| Experimental: Arm 5<br>High dose formulation A and SIIV | Biological: Formulation A<br>* RSV vaccine<br>|
| Experimental: Arm 6<br>High dose formulation B and SIIV | Biological: Formulation B<br>* Adjuvanted RSV vaccine<br>|
| Experimental: Arm 7<br>High dose formulation C and SIIV | Biological: Formulation C<br>* RSV vaccine<br>|
| Placebo Comparator: Arm 8<br>Placebo and SIIV | Biological: Placebo<br>* Placebo<br>|
| Experimental: M0M2 Arm 1<br>High dose formulation B | Biological: Formulation B<br>* Adjuvanted RSV vaccine<br>|
| Placebo Comparator: M0M2 Arm 2<br>Placebo | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Cohort: Percentage of Participants With Local Reactions Within 14 Days After Vaccination 1 | Local reactions included redness, swelling, and pain at the injection site (left arm) recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units (range: 1 to 20, and greater than [>] 21). 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 activity), moderate (interferes with activity) and severe (prevented daily activity). | Within 14 days after Vaccination 1 | 
| Primary Cohort: Percentage of Participants With Systemic Events Within 14 Days After Vaccination 1 | Systemic events included fever, fatigue/tiredness, headache, vomiting, nausea, diarrhea, muscle pain and joint pain recorded by participants in an e-diary. Fever was graded as: mild (38.0 to 38.4 degrees [deg] Celsius [C]), moderate (38.5 to 38.9 deg C), severe (39 deg C to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle 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 (1-2 times in 24 hours [h]), moderate (>2 times in 24h) and severe (required intravenous hydration). Diarrhea was graded as: mild (2-3 loose stools in 24h), moderate (4-5 loose stools in 24h) and severe (6 or more loose stools in 24h). | Within 14 days after Vaccination 1 | 
| Primary Cohort: Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination 1 | An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. AEs included both serious and non-serious adverse events. | Within 1 month after Vaccination 1 | 
| Primary Cohort: Percentage of Participants With Medically Attended Adverse Events (MAEs) and Serious Adverse Events (SAEs) Through 12 Months After Vaccination 1 | An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. A SAE is any untoward medical occurrence at any dose: results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect. | Up to 12 months after Vaccination 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | GMTs of RSV A and RSV B antigens were measured using neutralizing assay. Titers above the lower limit of quantitation (LLOQ) were considered accurate and their quantitated values were reported. The neutralizing titer LLOQ values were: A = 50 and B = 70. Assay results below the LLOQ were set to 0.5 × LLOQ. | Before vaccination and 1 Month after Vaccination 1 | 
| 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 | The HAI and neutralizing titer LLOQ value for each strain was 1:10. Assay results below the LLOQ were set to 0.5 × LLOQ. The analysis was performed on following strains: H1N1 A/Michigan, H3N2 A/Brisbane, B/Phuket for HAI and H3N2/Brisbane for neutralizing assay. | Before vaccination and 1 Month after Vaccination 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Respiratory tract infection, RSV, Adjuvant, vaccine