A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 When Administered Concomitantly With Influenza Vaccine in Adults 50 Years of Age or Older (V116-005, STRIDE-5)

Study Overview
=================
Brief Summary
-----------------
This a study of V116 in adults ≥50 years of age who concomitantly received Influenza vaccine. The primary objectives of this study are to evaluate the safety, tolerability, and immunogenicity of V116 when administered concomitantly with Quadrivalent Influenza vaccine (QIV) compared with V116 administered sequentially with QIV. The primary hypotheses state that immune responses to V116 and to QIV are non-inferior when administered concomitantly as compared with sequential administration as measured by serotype-specific opsonophagocytic activity (OPA) and hemagglutination inhibition (HAI) geometric mean titers (GMTs) at 30 days postvaccination.

Official Title
-----------------
A Phase 3 Randomized, Double-blind, Placebo-Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 When Administered Concomitantly With Influenza Vaccine in Adults 50 Years of Age or Older

Conditions
-----------------
Pneumonia, Pneumococcal

Intervention / Treatment
-----------------
* Biological: V116
* Biological: QIV
* Biological: Matching Placebo for V116


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females: Not pregnant or a breast feeding and not a woman of childbearing potential (WOCBP) or a WOCBP agrees to use contraception or remain abstinent Exclusion Criteria: Has a history of invasive pneumococcal disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years Has a known hypersensitivity to any component of V116 or any influenza vaccine, including diphtheria toxoid Has a known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease Has a coagulation disorder contraindicating intramuscular vaccination Has a known malignancy that is progressing or has required active treatment <3 years before enrollment Is expected to receive any pneumococcal vaccine during the study outside of the protocol Received any pneumococcal vaccine <12 months prior to enrollment (including pneumococcal 13-valent conjugate vaccine [PCV13] followed by pneumococcal 23-valent polysaccharide vaccine [PPSV23] and PPSV23 followed by PCV13) Had prior administration of PCV15 or PCV20 Received any influenza vaccine <6 months prior to enrollment or is expected to receive any influenza vaccine during the study outside of the protocol Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention ≥14 days before receipt of study vaccine Is currently receiving immunosuppressive therapy, including chemotherapeutic agents or other immunotherapies/immunomodulators used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease Received any nonlive vaccine ≤14 days before receipt of study vaccine or is scheduled to receive any nonlive vaccine ≤30 days after receipt of study vaccine Received any live virus vaccine ≤30 days before receipt of study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of study vaccine Received a blood transfusion or blood products, including immunoglobulin ≤6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product before the Day 30 postvaccination blood draw is complete Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study

Ages Eligible for Study
-----------------
Minimum Age: 50 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concomitant group (V116 + QIV followed by placebo)<br>Participants will receive a single 0.5 mL intramuscular (IM) injection of V116 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30 | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>Biological: QIV<br>* Single 0.5 mL IM injection<br>Biological: Matching Placebo for V116<br>* Single 0.5 mL of sterile saline IM injection<br>|
| Experimental: Sequential group (placebo + QIV followed by V116)<br>Participants will receive a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V116 on Day 30 | Biological: V116<br>* Pneumococcal 21-valent conjugate vaccine with 4 μg of each of the pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution<br>Biological: QIV<br>* Single 0.5 mL IM injection<br>Biological: Matching Placebo for V116<br>* Single 0.5 mL of sterile saline IM injection<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Solicited Injection-site Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The solicited injection-site AEs include tenderness/injection-site pain, injection-site redness/injection-site erythema, and injection-site swelling/injection-site swelling. | Up to 5 days post-vaccination | 
| Percentage of Participants with Solicited Systemic AEs | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The solicited systemic AEs include muscle aches all over body/myalgia, headache, and tiredness/fatigue. | Up to 5 days post-vaccination | 
| Percentage of Participants with Vaccine-related Serious Adverse Events (SAEs) | A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that were reported to be at least possibly related by the investigator to study vaccination will be summarized. | Up to  210 days | 
| Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Responses | Opsonophagocytic activity (OPA) for the serotypes in V116 will be determined using a multiplexed opsonophagocytic assay (MOPA). | 30 days after V116 vaccination (Day 30 for concomitant group and Day 60 for sequential group) | 
| GMT of Influenza Strain-specific Hemagglutination Inhibition (HAI) | Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) | The GMC of serotype-specific IgG for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using an pneumococcal electrochemiluminescence (Pn ECL) assay. | 30 days after V116 vaccination (Day 30 for concomitant group and Day 60 for sequential group) | 
| Geometric Mean Fold Rise (GMFR) of Serotype-specific OPA | Activity for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using a MOPA. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. | Day 1 (Baseline) and Day 30 post-vaccination for concomitant group. Day 1 (Baseline) and Day 60 post-vaccination for sequential group. | 
| Geometric Mean Fold Rise (GMFR) of Serotype-specific IgG | Activity for the serotypes contained in V116 (serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) will be determined using an Pn ECL assay. GMFR is defined as the geometric mean of the ratio of concentration at Day 30 after vaccination divided by concentration at baseline. | Day 1 (Baseline) and Day 30 post-vaccination for concomitant group. Day 1 (Baseline) and Day 60 post-vaccination for sequential group. | 
| GMFR in Influenza Strain-specific HAI | Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. GMFR is GMT 30 days after vaccination / GMT at Baseline. | Day 1 (Baseline) and Day 30 | 
| Percentage of Participants with Influenza Strain-specific HAI Titer ≥1:40 | Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. | Day 30 | 
| Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI | Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. | Day 30 |