Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2/V114-026)

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the safety and immunogenicity of a 3-dose schedule (2-dose primary series followed by a toddler dose) of pneumococcal conjugate vaccine (PCV) as one of the currently recommended schedules by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) on Immunizations and practiced in many countries. The primary hypotheses are that V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes based on response rates and on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; that V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on the response rates and on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 3; and that Vaxelis™ administered concomitantly with V114 is non-inferior to Vaxelis™ administered concomitantly with Prevenar 13™ at 30 days following Dose 3 for each antigen included in Vaxelis™.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Active-comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 3-dose Regimen of V114 in Healthy Infants (PNEU-PED-EU-2)

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Drug: V114
* Drug: Prevenar 13™
* Drug: Vaxelis™
* Drug: M-M-R®II
* Drug: VARIVAX™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female, approximately 3 months of age, from 70 days to 111 days inclusive, at the time of signing the informed consent. Has 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: Was born prior to 37 weeks of gestation. Has a history of invasive pneumococcal disease (IPD) or known history of other culture positive pneumococcal disease. Has a known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV), any component of the licensed pediatric vaccines to be administered concomitantly in the study, or any diphtheria toxoid containing vaccine. Has any contraindication to the concomitant study vaccines being administered in the study. Has a known or suspected impairment of immunological function. Has a history of congenital or acquired immunodeficiency. Has, or his/her mother has, a documented human immunodeficiency virus (HIV) infection. Has, or his/her mother has, a documented hepatitis B surface antigen - positive test. Has known or history of functional or anatomic asplenia. Has failure to thrive based on the clinical judgement of the investigator. Has a bleeding disorder contraindicating intramuscular vaccination. Has a 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). Has a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders. Has received a dose of any pneumococcal vaccine prior to study entry. Has received >1 dose of monovalent hepatitis B vaccine or hepatitis B-based combination vaccine prior to study entry. Has received a dose of any acellular pertussis- or whole cell pertussis-based combination vaccines, Haemophilus influenza type b conjugate vaccine, poliovirus vaccine, or any other combination thereof, prior to study entry. Has received a blood transfusion or blood products, including immunoglobulins. Has 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; these will be reviewed on a case by-case basis for approval by the Sponsor. Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study. Reasons may include, but are not limited to, being unable to keep appointments or planning to relocate during the study. Is or has an immediate family member (e.g., parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study.

Ages Eligible for Study
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Minimum Age: 70 Days
Maximum Age: 111 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: Treatment
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 Visit 1, 2, and 4 (approximately 3, 5, and 12 months of age). As part of the study design, participants will also receive other pediatric vaccines, including Vaxelis™ (0.5 mL single dose at Visits 1, 2, and 4); M-M-R™II (0.5 mL single dose at Visit 4); and VARIVAX™ (0.5 mL single dose at Visit 4, except participants in Norway and Denmark, who will receive a second dose of VARIVAX™ at Visit 5, according to local vaccination requirements). | Drug: V114<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F, serotype 6B and aluminum phosphate adjuvant in each 0.5 mL dose.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;Drug: Vaxelis™<br>* Intramuscular 0.5 mL single dose<br>Drug: M-M-R®II<br>* Subcutaneous 0.5 mL single dose<br>* Other names: Measles, Mumps, and Rubella Virus Vaccine Live;Drug: VARIVAX™<br>* Subcutaneous 0.5 mL single dose<br>* Other names: Varicella Vaccine Live;|
| Active Comparator: Prevenar 13™<br>Participants will receive a single 0.5 mL IM injection of Prevenar 13™ at Visit 1, 2, and 4 (approximately 3, 5, and 12 months of age). As part of the study design, participants will also receive other pediatric vaccines, including Vaxelis™ (0.5 mL single dose at Visits 1, 2, and 4); M-M-R™II (0.5 mL single dose at Visit 4); and VARIVAX™ (0.5 mL single dose at Visit 4, except participants in Norway and Denmark, who will receive a second dose of VARIVAX™ at Visit 5, according to local vaccination requirements). | Drug: Prevenar 13™<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, serotype 6B in each 0.5. mL dose.<br>* Other names: Prevnar 13™;Drug: Vaxelis™<br>* Intramuscular 0.5 mL single dose<br>Drug: M-M-R®II<br>* Subcutaneous 0.5 mL single dose<br>* Other names: Measles, Mumps, and Rubella Virus Vaccine Live;Drug: VARIVAX™<br>* Subcutaneous 0.5 mL single dose<br>* Other names: Varicella Vaccine Live;|

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. | Day 1 to Day 14 after each 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). | Day 1 to Day 14 after each 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 approximately 6 months after Dose 3 (up to approximately 16 months) | 
| Percentage of Participants Meeting Serotype-specific Immunoglobulin G (IgG) Threshold Value of ≥0.35 μg/mL 30 Days After Dose 3 | The geometric mean concentration (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 Prevenar 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. | 30 days after Dose 3 | 
| Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) 30 Days After Dose 3 | 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 Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex electrochemiluminescence (ECL) assay. | 30 days after Dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting Specified Vaxelis™ Antigen Reponses 30 Days After Dose 3 | Antigen-specific response rates in participants administered V114 concomitantly with Vaxelis™ were compared with response rates in participants administered Prevenar 13™ concomitantly with Vaxelis™, and the percentages of participants meeting specified Vaxelis™ antigen responses recorded. Antigens in Vaxelis™ include: diphtheria toxoid, tetanus toxoid, pertussis toxin (PT), pertussis filamentous hemagglutinin (FHA), pertussis fimbriae 2/3 (FIM 2/3), pertussis pertactin (PRN), Haemophilus influenzae type b polyribosylribitol phosphate (Hib-PRP), hepatitis B surface antigen (HBsAg), and poliovirus serotypes 1, 2, and 3. | 30 days after Dose 3 | 
| Percentage of Participants Meeting Serotype-specific IgG Threshold Value of ≥0.35 μg/mL 30 Days After Dose 2 | 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 Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay. | 30 days after Dose 2 | 
| GMC of Serotype-specific IgG 30 Days After Dose 2 | 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 Prevenar 13™ and 2 serotypes (22F and 33F) unique to V114 were quantitated from participants' sera by a multiplex ECL assay. Immunoglobulin G for the 15 serotypes contained in V114 vaccine was determined using a PnECL assay. | 30 days after Dose 2 | 
| Percentage of Participants Meeting Specified Opsonophagocytic Activity (OPA) Responses 30 Days After Dose 3 | OPA for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes unique to V114 (22F and 33F) was measured using a multiplex opsonophagocytic assay (MOPA). | 30 days after Dose 3 | 
| Geometric Mean Titers (GMTs) of Serotype-specific OPA 30 Days After Dose 3 | Sera from participants was used to measure GMT of the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevenar 13™ and 2 serotypes unique to V114 (22F and 33F) was determined using a MOPA. | 30 days after Dose 3 |