A Study of Pneumococcal Conjugate Vaccine (V114) Compared to a Marketed Vaccine (V114-003)

Study Overview
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Brief Summary
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This study will evaluate whether the aluminum-adjuvanted or the non-adjuvanted formulation of the candidate pneumococcal vaccine (V114) is non-inferior to Prevnar 13® based on immune responses to the 13 serotypes in common Prevnar 13®

Official Title
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A Multicenter, Double-Blind Study of the Safety, Tolerability, and Immunogenicity of Pneumococcal Conjugate Vaccine (V114) Compared to Prevnar 13™ in Healthy Infants

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114 Aluminum-adjuvanted
* Biological: V114 Non-adjuvanted
* Biological: Prevnar 13®


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy infants ≥ 42 days to ≤ 89 days. Participant's parent/legal guardian understands the study procedures, alternate treatments available and risks involved with the study, and voluntarily agrees to allow the child to participate by giving written informed consent. Afebrile, with a rectal temperature <38.1°C (<100.5°F) or axillary temperature <37.8°C (<100.0°F) on day of vaccination. Participant's parent/legal guardian is able to read, understand, and complete study questionnaires (i.e., the Vaccination Report Card). Participant is able to attend all scheduled visits and to comply with the study procedures. Participant's parent/legal guardian has access to a telephone. Exclusion Criteria: Prior administration of any pneumococcal vaccine. Known hypersensitivity to any component of the pneumococcal conjugate vaccine. Known or suspected impairment of immunological function. Participant has a history of congenital or acquired immunodeficiency (e.g., splenomegaly). Participant or his/her mother has documented human immunodeficiency virus (HIV) infection. Functional or anatomic asplenia. History of autoimmune disease including multiple sclerosis (MS), systemic lupus, polymyositis, inclusion body myositis, dermatomyositis, Hashimoto's thyroiditis, Sjogren's syndrome, rheumatoid arthritis, other autoimmune disorders. Known neurologic or cognitive behavioral disorders including multiple sclerosis (MS), MS-like disease, encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive developmental disorder, and related disorders. Use of any immunosuppressive therapy (Note: topical and inhaled/nebulized steroids are permitted). Participants on intramuscular, oral, or intravenous corticosteroid treatment should be excluded if they are receiving or expected to receive in the period from 30 days prior to Visit 1 through Visit 6 (30 days post-dose 4) more than 2 mg/kg per day of prednisone (or its equivalent), or more than 20 mg/d if they weigh more than 10 kg and are not otherwise immunocompromised. Excluded immunosuppressive therapies also include chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation, or autoimmune disease. Participant has received other licensed non-live vaccines within the 14 days before receipt of study vaccine. Participant has received a licensed live virus vaccine within the 30 days prior of receipt of study vaccine. Prior receipt of a blood transfusion or blood products, including immunoglobulins. Investigational drugs or vaccines received within the 2 months before receipt of study vaccine. Participation in another clinical study within 42 days before the beginning or anytime during the duration of the current clinical study. History of invasive pneumococcal disease (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease. A recent febrile illness (rectal temperature ≥38.1°C [≥100.5°F]) occurring within 72 hours before receipt of study vaccine. History of failure to thrive. Participant has a coagulation disorder contraindicating IM vaccination. Participant and his/her mother have documented hepatitis B surface antigen-positive. Any infant who cannot be adequately followed for safety according to the protocol plan. Participant's parent/legal guardian is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study. Any other reason that in the opinion of the investigator may interfere with the evaluation required by the study.

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

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V114 Aluminum-adjuvanted<br>Four intramuscular (IM) doses at 0.5 mL of aluminum-adjuvanted V114 pneumococcal conjugate vaccine at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 Aluminum-adjuvanted<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.2 mcg each), serotype 6B (4.4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>|
| Experimental: V114 Non-adjuvanted<br>Four IM doses at 0.5 mL of non-adjuvanted V114 pneumococcal conjugate vaccine at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 Non-adjuvanted<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), and serotype 6B (4 mcg) in each 0.5 mL dose.<br>|
| Active Comparator: Prevnar 13®<br>Four IM doses at 0.5 mL of Prevnar 13® at 2, 4, 6, and 12 to 15 months of age. | Biological: Prevnar 13®<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), serotype 6B (4.4 mcg each) and aluminum phosphate adjuvant (125 mcg) in each 0.5. mL dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving the Immunoglobulin G (IgG) Serotype-specific ≥0.35 μg/mLThreshold Value for Postvaccination 3 | Percentage of participants meeting the serotype-specific IgG reference level (an antibody concentration measured by the pneumococcal polysaccharide electrochemiluminescence [Pn ECL] assay corresponding to the World Health Organization enzyme-linked immunosorbent assay [WHO ELISA] ≥ 0.35 μg/mL) (post-dose 3) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. | One month postvaccination 3 | 
| IgG Geometric Mean Concentrations (GMCs) for Postvaccination 3 | The IgG GMCs were evaluated as measured in the Pn ECL assay, for recipients of adjuvanted V114, non-adjuvanted V114, and Prevnar 13® (post-dose 3) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. | One month postvaccination 3 | 
| IgG GMCs for Postvaccination 4 | The IgG GMCs were evaluated as measured in the Pn ECL assay, for recipients of adjuvanted V114, non-adjuvanted V114, and Prevnar 13® (post-dose 4) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. | One month postvaccination 4 | 
| Number of Participants With an Adverse Event (AE) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse experience. | Up to Day 14 postvaccination | 
| Number of Participants With an Injection-site AE | Injection-site AEs reported by > 0% of participants in one or more vaccination groups were assessed. | Up to Day 14 postvaccination | 
| Number of Participants With a Systemic AE | Systemic AEs reported by > 0% of participants in one or more vaccination groups were assessed. | Up to Day 14 postvaccination | 
| Number of Participants With a Serious Adverse Event (SAE) | An SAE is an AE that results in death, is life threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. | Up to one month after last dose of study vaccine | 
| Number of Participants Who Discontinued the Study Due to an AE | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse experience. | Up to Day 14 postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Opsonophagocytic Killing Activity (OPA) Titer ≥ 8 as Measured by Fourfold Multiplexed Opsonization Assay (MOPA4) for Postvaccination 3 | The antibody responses as measured by MOPA4 (post-dose 3) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. Functional antibody activity was assessed only in a subset of the vaccinated participants, thus the study was not powered for assessing non-inferiority with respect to the OPA antibody responses. | One month postvaccination 3 | 
| Percentage of Participants With OPA Titer ≥ 8 as Measured by MOPA4 for Postvaccination 4 | The antibody responses as measured by MOPA4 (post-dose 4) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. Functional antibody activity was assessed only in a subset of the vaccinated participants, thus the study was not powered for assessing non-inferiority with respect to the OPA antibody responses. | One month postvaccination 4 | 
| OPA Geometric Mean Titers (GMTs) as Measured by MOPA4 for Postvaccination 3 | The antibody responses as measured by MOPA4 (post-dose 3) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. The OPA antibody responses included the percentage of participants with OPA titer and the GMTs. Functional antibody activity was assessed only in a subset of the vaccinated participants, thus the study was not powered for assessing non-inferiority with respect to the OPA antibody responses. | One month postvaccination 3 | 
| OPA GMTs as Measured by MOPA4 for Postvaccination 4 | The antibody responses as measured by MOPA4 (post-dose 4) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. Functional antibody activity was assessed only in a subset of the vaccinated participants, thus the study was not powered for assessing non-inferiority with respect to the OPA antibody responses. | One month postvaccination 4 | 
| Percentage of Participants Achieving the IgG Serotype-specific Threshold Value of ≥0.35 μg/mL for Postvaccination 4 | Percentage of participants achieving World Health Organization (WHO) predefined antibody threshold as measured by the pneumococcal polysaccharide electrochemiluminescence (Pn ECL) assay corresponding to the WHO enzyme-linked immunosorbent assay (ELISA) value of ≥ 0.35μg/mL (post-dose 4) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. | One month postvaccination 4 | 
| Percentage of Participants Achieving the IgG Serotype-specific Threshold Value of ≥1.0 μg/mL for Postvaccination 4 | Percentage of participants achieving WHO predefined antibody threshold as measured by the Pn ECL assay corresponding to the WHO enzyme-linked immunosorbent assay (ELISA) value of ≥ 1.0 μg/mL (post-dose 4) for the 13 serotypes in common with PREVNAR 13® (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) and the 2 serotypes (serotypes 22F and 33F) not in common with PREVNAR 13®. | One month postvaccination 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Invasive pneumococcal disease, Pneumonia, Pneumococcal conjugate vaccine