A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Two Lots of V114 in Healthy Infants (V114-008)

Study Overview
=================
Brief Summary
-----------------
This study is designed to evaluate the safety, tolerability, and immunogenicity of two different lots of V114 in healthy infants 6 to 12 weeks (>=42 days to <=90 days) of age. The primary hypothesis of the study is that the proportion of participants receiving V114 who have serotype specific IgG >=0.35 mcg/mL for each of pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F at 1 month after Dose 3 is non-inferior to that for recipients of Prevnar 13™.

Official Title
-----------------
A Phase II, Double-Blind, Randomized, Multicenter Trial to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Compared to Prevnar 13™ in Healthy Infants

Conditions
-----------------
Pneumococcal Infections

Intervention / Treatment
-----------------
* Biological: V114 Lot 1
* Biological: V114 Lot 2
* Biological: Prevnar 13™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infant approximately 2 months of age (42 days to 90 days), inclusive In good health Exclusion Criteria: Prior administration of any pneumococcal vaccine Known hypersensitivity to any component of the pneumococcal conjugate vaccine or any diphtheria toxoid-containing vaccine Known or suspected impairment of immunological function History of congenital or acquired immunodeficiency (eg, splenomegaly) Mother has documented human immunodeficiency virus (HIV) infection Mother has documented hepatitis B surface antigen-positive test result Known or history of functional or anatomic asplenia History of failure to thrive History of a coagulation disorder History of autoimmune disease Known neurologic or cognitive behavioral disorder Expects to require systemic corticosteroids within 30 days after each vaccination during the trial Prior administration of a blood transfusion or blood products, including immunoglobulin Participated in another clinical trial of an investigational product History of invasive pneumococcal disease or known history of other culture-positive pneumococcal disease

Ages Eligible for Study
-----------------
Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

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 |
| --- | --- |
| Experimental: V114 Lot 1<br>Infants will receive a 0.5 mL intramuscular injection of V114 Lot 1 at 2, 4, 6, and 12-15 months of age (Study Day 1, Month 2, Month 4, and Month 10-13) | Biological: V114 Lot 1<br>* Lot 1: Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose<br>* Other names: V114-1;|
| Experimental: V114 Lot 2<br>Infants will receive a 0.5 mL intramuscular injection of V114 Lot 2 at 2, 4, 6, and 12-15 months of age (Study Day 1, Month 2, Month 4, and Month 10-13) | Biological: V114 Lot 2<br>* Lot 2: Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose<br>* Other names: V114-2;|
| Active Comparator: Prevnar 13™<br>Infants will receive a 0.5 mL intramuscular injection of Prevnar 13™ at 2, 4, 6, and 12-15 months of age (Study Day 1, Month 2, Month 4, and Month 10-13) | Biological: Prevnar 13™<br>* Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg) in each 0.5 ml dose<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving the Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Threshold Value of ≥0.35 µg/mL for the 13 Common Serotypes in V114 and Prevnar 13™: 1 Month Post Vaccination 3 | Serotype-specific pneumococcal IgG antibody was measured using the Meso-Scale Discovery (MSD) Pneumococcal electrochemiluminescence assay (Pn ECL). The percentage of participants with serotype-specific IgG ≥0.35 µg/mL was summarized for each serotype. | 1 month post vaccination 3 (Month 5) | 
| Geometric Mean Concentration of Serotype-specific Pneumococcal IgG Antibody for the 13 Common Serotypes in V114 and Prevnar 13™ and the 2 Serotypes Unique to V114: 1 Month Post Vaccination 3 | Serotype-specific pneumococcal IgG antibody will be assayed using the Meso-Scale Discovery (MSD) Pn electrochemiluminescence assay. The geometric mean concentration (GMC) of serotype-specific IgG will be assessed. | 1 month post Vaccination 3 (Month 5) | 
| Percentage of Participants Who Experience at Least 1 Adverse Event | An adverse event (AE) is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with one or more AEs was assessed. | Up to 1 month post Vaccination 4 (up to 14 months) | 
| Percentage of Participants Who Discontinued From the Study Due to an Adverse Event | The percentage of participants who discontinued the study because of an AE (as defined above) was assessed. | Up to 1 month post Vaccination 4 (up to 14 months) | 
| Percentage of Participants With a Solicited Injection-site Adverse Event | Injection-site AEs solicited on the Vaccine Report Card were redness, swelling, hard lump, and pain/tenderness. The percentage of participants with 1 or more solicited injection-site AEs was assessed. | Up to 14 days post any vaccination | 
| Percentage of Participants With a Solicited Systemic Adverse Event | Systemic AEs solicited on the Vaccine Report Card were fever, irritability, drowsiness, hive/welts, and appetite loss. The percentage of participants with 1 or more solicited systemic AEs was assessed. | Up to 14 days post any vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration of Serotype-specific Pneumococcal IgG Antibody for the 13 Common Serotypes in V114 and Prevnar and the 2 Serotypes Unique to V114: Pre-vaccination 4 | Serotype-specific pneumococcal IgG antibody was assayed using the MSD Pn electrochemiluminescence assay. | Before Vaccination 4 (Month 10 to 13) | 
| Geometric Mean Concentration of Serotype-specific Pneumococcal IgG Antibody for the 13 Common Serotypes in V114 and Prevnar and the 2 Serotypes Unique to V114: 1 Month Post Vaccination 4 | Serotype-specific pneumococcal IgG antibody was assayed using the MSD Pn electrochemiluminescence assay. | 1 month post vaccination 4 (Month 11-14) |