Safety and Immunogenicity of 20vPnC Coadministered With SIIV in Adults ≥65 Years of Age

Study Overview
=================
Brief Summary
-----------------
Study of the safety and immunogenicity of 20vPnC and influenza vaccine administered at the same visit or separately

Official Title
-----------------
A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (20VPNC) WHEN COADMINISTERED WITH SEASONAL INACTIVATED INFLUENZA VACCINE (SIIV) IN ADULTS ≥65 YEARS OF AGE

Conditions
-----------------
Pneumococcal Disease

Intervention / Treatment
-----------------
* Biological: Experimental 20-valent pneumococcal conjugate vaccine (20vPnC)
* Other: Saline
* Biological: Influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants ≥65 years of age at the time of consent Adults determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study, including adults with preexisting stable disease Adults who have no history of ever receiving a pneumococcal vaccine, or have a history of receiving a licensed pneumococcal vaccination ≥6 months prior to first study vaccination. Exclusion Criteria: History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) Previous vaccination with any investigational pneumococcal vaccine, or planned receipt of any licensed or investigational pneumococcal vaccine through study participation. Vaccination with any influenza or pneumococcal vaccine <6 months before investigational product administration, or planned receipt of any licensed or investigational non-study influenza vaccine during study participation. -- Serious chronic disorder, that in the investigator's opinion would make the participant inappropriate for entry into the study Other acute or chronic medical or psychiatric condition 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

Ages Eligible for Study
-----------------
Minimum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Coadministration Group<br>Participants receive injections of pneumococcal vaccine (20vPnC) and influenza vaccine at the same visit, and then receive an injection of saline 1 month later. | Biological: Experimental 20-valent pneumococcal conjugate vaccine (20vPnC)<br>* Experimental 20-valent pneumococcal conjugate vaccine (20vPnC)<br>Other: Saline<br>* Normal saline for injection<br>Biological: Influenza vaccine<br>* Seasonal inactivated influenza vaccine (SIIV)<br>|
| Active Comparator: Separate Administration Group<br>Participants receive injections of saline and influenza vaccine at the same visit, and then receive an injection of 20vPnC 1 month later. | Biological: Experimental 20-valent pneumococcal conjugate vaccine (20vPnC)<br>* Experimental 20-valent pneumococcal conjugate vaccine (20vPnC)<br>Other: Saline<br>* Normal saline for injection<br>Biological: Influenza vaccine<br>* Seasonal inactivated influenza vaccine (SIIV)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions Within 10 Days After Vaccination With 20vPnC | Local reactions were collected at the 20vPnC injection sites after Vaccination 1 and Vaccination 2 and were recorded by the participants using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm) and severe (>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Percentage of participants with local reactions at the 20vPnC injection site in the Coadministration group and the Separate administration group and the associated 2-sided 95% confidence interval (CI) based on the Clopper and Pearson method was presented. | Within 10 days after Vaccination 1 for Coadministration group and within 10 days after Vaccination 2 for Separate Administration group | 
| Percentage of Participants With Systemic Events Within 7 Days After Each Vaccination By Each Vaccine | Systemic events including fever, fatigue, headache, muscle pain and joint pain were recorded by participants using an e-diary. Fever was defined as temperature >=38.0 degree Celsius (C) and categorized as >=38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, 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). Percentage of participants with systemic events within 7 days after each vaccination and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. | Within 7 days after each vaccination | 
| Percentage of Participants With Adverse Events (AEs) Within 1 Month After Each Vaccination by Each Vaccine | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | Within 1 month after each vaccination | 
| Percentage of Participants With Serious Adverse Events (SAEs) From the First Vaccination up to 6 Months After Last Vaccination | An SAE was defined as any untoward medical occurrence that, at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect or that is considered to be an important medical event. Percentage of participants with SAEs and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. | From Day 1 up to 6 months after last Vaccination (i.e. up to 7 months) | 
| Percentage of Participants With Newly Diagnosed Chronic Medical Condition (NDCMC) up to 6 Months After Last Vaccination | An NDCMC was defined as a significant disease or medical condition, not previously identified, that is expected to be persistent or is otherwise long-lasting in its effects. Percentage of participants with NDCMC and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. | Up to 6 months after last Vaccination (i.e. up to 7 months) | 
| Model-Based Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) at 1 Month After Vaccination With 20vPnC | OPA titers were measured from serum samples for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F,8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F. GMTs and 2-sided CIs were calculated by exponentiating the LS means and the corresponding CIs based on analysis of log-transformed OPA titers using a regression model | 1 month after the 20vPnC administration in each group (1 month after Vaccination 1 in the Coadministration group and 1 month after Vaccination 2 in the Separate Administration group). | 
| Model-Based Hemagglutination Inhibition (HAI) Strain Specific Geometric Mean Titers (GMT) at 1 Month After Vaccination With SIIV | HAI titers to the influenza strains (A/H1N1, A/H3N2, B/Victoria, and B/Phuket) in the SIIV administered sera samples was collected and reported in this outcome measure at 1 month after Vaccination 1. GMTs and 2-sided CIs were calculated by exponentiating the LS means and the corresponding CIs based on analysis of log-transformed HAI titers using a regression model. | At 1 month after Vaccination 1 with SIIV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Greater Than or Equal to (≥4) Fold Rise in Serotype-Specific Opsonophagocytic Activity (OPA) Titers From Before Vaccination to 1 Month After Vaccination With 20vPnC | OPA titers were measured from serum samples for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F,8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F. Percentage of participants with >=4 fold rise in serotype-specific OPA titers from before vaccination to 1 month after vaccination with 20vPnC and the associated 2-sided 95% CI based on the Clopper and Pearson method was presented. | Before Vaccination 1 to 1 month after 20vPnC vaccination in both groups (i.e., 1 month after Vaccination 1 in Coadministration group and 1 month after Vaccination 2 in Separate Administration group) | 
| Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Fold Rise (GMFR) From Before Vaccination to 1 Month After Vaccination With 20vPnC | OPA titers were measured from serum samples for serotypes: 1, 3, 4, 5, 6A, 6B, 7F,8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with 20vPnC. GMFRs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the OPA titers or fold rises and the corresponding CIs. | Before Vaccination 1 to 1 month after 20vPnC vaccination in both groups (i.e., 1 month after Vaccination 1 in Coadministration group and 1 month after Vaccination 2 in Separate Administration group) | 
| Hemagglutination Inhibition (HAI) Strain Specific Geometric Mean Fold Rise (GMFR) Before Vaccination to 1 Month After Vaccination With SIIV | HAI titers were measured from serum samples for serotypes A/H1N1, A/H3N2, B/Victoria, B/Phuket. GMFR was calculated as geometric mean of fold rise from before vaccination on Day 1 to 1 month after vaccination with SIIV. GMFRs were calculated for participants with non-missing values both before and after vaccination. | Before Vaccination 1 to 1 month after Vaccination 1 with SIIV |