A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety and tolerability of V114 and Prevnar 13™ in healthy infants. This study will include both full-term infants (≥37 weeks gestational age) and premature infants (<37 weeks gestational age). Premature infants will be included in a Premature Infant Immunogenicity Substudy, which will assess immunogenicity and safety following administration of V114 or Prevnar 13™.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety and Tolerability of V114 in Healthy Infants (PNEU-LINK)

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: Prevnar 13™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy (based on a review of medical history and physical examination) based on the clinical judgment of the investigator Male or female approximately 2 months of age, from 42 days to 90 days inclusive, at the time of obtaining the informed consent Have a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent. Exclusion Criteria: History of Invasive Pneumococcal Disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease Known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV) or any diphtheria toxoid containing vaccine Known or suspected impairment of immunological function History of congenital or acquired immunodeficiency Has or his/her mother has a documented human immunodeficiency virus (HIV) infection Known or history of functional or anatomic asplenia Failure to thrive based on the clinical judgment of the investigator Known coagulation disorder contraindicating intramuscular vaccination History of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Behcet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, type 1 diabetes mellitus, or other autoimmune disorders) Known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders Received a dose of any pneumococcal vaccine prior to study entry Received a blood transfusion or blood products, including immunoglobulins, before receipt of first dose of study vaccine Participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included. Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study Has an immediate family member who is investigational site or Sponsor staff directly involved with this study.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 90 Days

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V114<br>Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 at approximately 2 months of age (Vaccination 1); approximately 4 months of age (Vaccination 2); approximately 6 months of age (Vaccination 3); and approximately 12-15 months of age (Vaccination 4). | Biological: V114<br>* V114 pneumococcal capsular polysaccharide 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>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;|
| Active Comparator: Prevnar 13™<br>Participants will receive a single 0.5 mL IM injection of Prevnar 13™ at approximately 2 months of age (Vaccination 1); approximately 4 months of age (Vaccination 2); approximately 6 months of age (Vaccination 3); and approximately 12-15 months of age (Vaccination 4). | Biological: Prevnar 13™<br>* Prevnar 13™ pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each) and 6B (4.4 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 With a Solicited Injection-site Adverse Event | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs included injection-site erythema (redness), injection-site induration (hard lump), injection-site pain (tenderness), and injection-site swelling. | Up to Day 14 after each study vaccination | 
| Percentage of Participants With a Solicited Systemic Adverse Event | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs included decreased appetite, irritability, somnolence (drowsiness), and urticaria (hives or welts). | Up to Day 14 after each study vaccination | 
| Percentage of Participants With a Vaccine-related Serious Adverse Event | A serious adverse event (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. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were summarized. | Up to 6 months after Vaccination 4 (up to 19 months after Vaccination 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) at 30 Days After Vaccination 3 (Premature Infants Only) | The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy. | 30 days after Vaccination 3 (approximately 5 months after Vaccination 1) | 
| GMC of Serotype-specific IgG Before Vaccination 4 (Premature Infants Only) | The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy. | Before Vaccination 4 (10-13 months after Vaccination 1) | 
| GMC of Serotype-specific IgG at 30 Days After Vaccination 4 (Premature Infants Only) | The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy. | 30 days after Vaccination 4 (11-14 months after Vaccination 1) | 
| Percentage of Participants Meeting Serotype-specific IgG Threshold of ≥0.35 μg/mL 30 Days After Vaccination 3 (Premature Infants Only) | The GMC of IgG serotype-specific antibodies to the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a pneumococcal electrochemiluminescence (PnECL) assay. This endpoint was part of a Premature Infant Immunogenicity Substudy. | 30 days after Vaccination 3 (approximately 5 months after Vaccination 1) |