Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-029)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V114 in healthy infants. The primary hypotheses are that: 1) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on response rates at 30 days following Dose 3; 2) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes compared with the lowest response rate of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 3) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes based on anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin g (IgG) geometric mean concentrations (GMCs) at 30 days following Dose 3; 4) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on the anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13™, excluding serotype 3, at 30 days following Dose 3; 5) V114 is non-inferior to Prevnar 13™ for the 13 shared serotypes between V114 and Prevnar 13™ based on anti-PnPs serotype-specific IgG GMCs at 30 days following Dose 4; and 6) V114 is non-inferior to Prevnar 13™ for the 2 unique V114 serotypes based on anti-PnPs serotype-specific IgG GMCs of the 2 unique V114 serotypes compared with the lowest IgG GMC of any of the shared serotypes in Prevnar 13, excluding serotype 3, at 30 days following Dose 4.

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 4-dose Regimen of V114 in Healthy Infants (PNEU-PED)

Conditions
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Pneumococcal Infections, Pneumococcal Vaccines

Intervention / Treatment
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* Biological: V114
* Biological: Prevnar 13™
* Biological: RotaTeq™
* Biological: Pentacel™
* Biological: RECOMBIVAX HB™
* Biological: VAQTA™
* Biological: MMR II™
* Biological: VARIVAX™
* Biological: HIBERIX™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is healthy (based on a review of medical history and physical examination) in the clinical judgement of the investigator 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: Has a 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. 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. Had a recent febrile illness (rectal temperature ≥38.1°C [=100.5°F] or axillary temperature ≥37.8°C [=100.0°F]) occurring within 72 hours prior to receipt of study vaccine.

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 receive 4 total 0.5 mL intramuscular (IM) vaccinations at  2, 4, 6, and 12 to 15 months of age. Participants will receive other vaccinations (i.e., RotaTeq™, Pentacel™, RECOMBIVAX HB™, VAQTA™, M-M-R II™, VARIVAX™, and HIBERIX™) as part of their vaccination schedule. | Biological: V114<br>* V114 15-valent pneumococcal conjugate vaccine containing 13 serotypes present in Prevnar 13® (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and 2 unique serotypes (22F and 33F) in each 0.5 mL intramuscular administration.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;Biological: RotaTeq™<br>* A total of 3 RotaTeq™ 2 mL oral dosings at  2,  4, and  6 months of age.<br>Biological: Pentacel™<br>* A total of 3 Pentacel™ 0.5 mL IM dosings at  2,  4, and  6 months of age.<br>Biological: RECOMBIVAX HB™<br>* A total of 3 RECOMBIVAX HB™ 0.5 mL IM dosings at  2,  4, and  6 months of age.<br>Biological: VAQTA™<br>* One VAQTA™ 0.5 mL IM dosing at 12 to 15 months of age.<br>Biological: MMR II™<br>* One MMR II™ 0.5 mL subcutaneous (SC) dosing at 12 to 15 months of age.<br>Biological: VARIVAX™<br>* One VARIVAX™ 0.5 mL SC dosing at 12 to 15 months of age.<br>Biological: HIBERIX™<br>* One HIBERIX™ 0.5 mL IM dosing at Visit 5.<br>|
| Active Comparator: Prevnar 13™<br>Participants receive 4 total 0.5 mL IM vaccinations at  2, 4, 6, and 12 to 15 months of age. Participants will also receive other vaccines (i.e., RotaTeq™, Pentacel™, RECOMBIVAX HB™, VAQTA™, M-M-R II™, VARIVAX™, and HIBERIX™) as part of their vaccination schedule. | Biological: Prevnar 13™<br>* Prevnar 13™ 13-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL IM administration.<br>Biological: RotaTeq™<br>* A total of 3 RotaTeq™ 2 mL oral dosings at  2,  4, and  6 months of age.<br>Biological: Pentacel™<br>* A total of 3 Pentacel™ 0.5 mL IM dosings at  2,  4, and  6 months of age.<br>Biological: RECOMBIVAX HB™<br>* A total of 3 RECOMBIVAX HB™ 0.5 mL IM dosings at  2,  4, and  6 months of age.<br>Biological: VAQTA™<br>* One VAQTA™ 0.5 mL IM dosing at 12 to 15 months of age.<br>Biological: MMR II™<br>* One MMR II™ 0.5 mL subcutaneous (SC) dosing at 12 to 15 months of age.<br>Biological: VARIVAX™<br>* One VARIVAX™ 0.5 mL SC dosing at 12 to 15 months of age.<br>Biological: HIBERIX™<br>* One HIBERIX™ 0.5 mL IM dosing at Visit 5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) in V114 Versus Prevnar 13™ | An AE is 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. Solicited injection-site AEs consisted of swelling, redness, pain or tenderness, and hard lump. | Up to 14 days after each vaccination with either V114 or Prevnar 13™ | 
| Percentage of Participants With Solicited Systemic AEs | An AE is 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. Solicited systemic AEs consisted of irritability, drowsiness, appetite lost, and hives or welts. | Up to 14 days after each vaccination with either V114 or Prevnar 13™ | 
| Percentage of Participants With Vaccine-Related Serious Adverse Events (SAEs) | An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an other important medical event. Any SAEs that are at least possibly related to vaccination are summarized. | From Day 1 up to 6 months after Vaccination 4 (up to 21 months) | 
| Percentage of Participants With Anti-Pneumococcal Polysaccharide (Anti-PnP) Immunoglobulin G (IgG) Antibody (Ab) ≥0.35 ug/mL One Month After Vaccination 3 | Anti-PnP serotype-specific IgG response rates for the 15 serotypes contained in V114 were measured with pneumococcal electrochemiluminescence (PnECL). The percentage of participants with IgG Ab ≥0.35 ug/mL are reported for each serotype. | One month after Vaccination 3 (Month 7) | 
| Geometric Mean Concentration (GMC) of Anti-PnP IgG Ab One Month After Vaccination 3 | The GMC of anti-PnP IgG Ab were measured with PnECL one month after vaccination 3 and reported for the 15 serotypes contained in V114. IgG GMCs were compared to the lowest in recipients of Prevnar 13™ excluding serotype 3 for the 2 serotypes unique to V114, and compared to the same serotypes for the 13 shared serotypes. | One month after Vaccination 3 (Month 7) | 
| GMC of Anti-PnP IgG Ab One Month After Vaccination 4 | The GMC of anti-PnP IgG Ab were measured with PnECL one month after vaccination 4 and reported for the 15 serotypes contained in V114. IgG GMCs were compared to the lowest in recipients of Prevnar 13™ excluding serotype 3 for the 2 serotypes unique to V114, and compared to the same serotypes for the 13 shared serotypes. | One month after Vaccination 4 (Month 13 to Month 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting Response Rate Criteria for Pentacel™-Specific (Anti-Diptheria Toxoid, Tetanus Toxoid, and Pertussis Antigens) Immunoglobulin G (IgG) Antibody (Ab) Geometric Mean Concentration (GMC) One Month After Vaccination 3 | Antibody responses to diphtheria toxoid, tetanus toxoid, and pertussis antigens were measured using Luminex Assay. The percentage of participants meeting specific criteria are summarized for each serotype. The serotype-specific response rate criteria are as follows: diphtheria toxoid: % ≥0.1 IU/mL; tetanus toxoid: % ≥0.1 IU/mL; pertussis toxin (PT): % ≥ 5 EU/mL; pertussis filamentous hemagglutinin (FHA): % ≥5 EU/mL; pertussis fimbrae types 2/3 (FIM 2/3): % ≥20 EU/mL; pertussis pertactin (PRN): % ≥5 EU/mL; poliovirus 1: % neutralizing antibody (NAb) ≥1:8 dilution; poliovirus 2: % NAb ≥1:8 dilution, poliovirus 3: % NAb ≥1:8 dilution; and Haemophilus influenzae Type B polyribosylribitol phosphate (Hib-PRP): % ≥0.15 ug/mL. | One month after Vaccination 3 (Month 7) | 
| Pertussis Antigen Immunoglobulin G (IgG) Antibody (Ab) Geometric Mean Concentration (GMC) One Month After Vaccination 3 | Pertussis antibody GMCs were measured using Luminex Assay. | One month after Vaccination 3 (Month 7) | 
| Hepatitis A Antibody Response Rate One Month After Vaccination 4 | Antibody response rates to hepatitis A were measured with hepatitis A virus enzyme immunoassay (HAV EIA). The percentage of participants with hepatitis A antigen ≥10 mIU/mL are reported. | One month after Vaccination 4 (Month 13 to Month 16) | 
| Measles, Mumps, and Rubella Antibody Response Rate One Month After Vaccination 4 | Antibody responses to measles were measured with the bulk measles IgG enzyme immunoassay (EIA). Antibody responses to mumps were measured with enzyme-linked immunosorbent assay (ELISA). Antibody responses to rubella were measured with Bulk Rubella IgG EIA. The percentage of participants with measles antigen ≥255 mIU/ML; mumps antigen ≥10 mumps Ab units/mL; and rubella antigen ≥10 IU/mL, are reported. | One month after Vaccination 4 (Month 13 to Month 16) | 
| Varicella-Zoster Virus (VZV) Antibody Response Rate One Month After Vaccination 4 | Antibody responses to varicella-zoster virus were measured with glycoprotein enzyme-linked immunosorbent assay (gpELISA). The percentage of participants with VZV antigen ≥5 gpELISA units/mL are reported. | One month after Vaccination 4 (Month 13 to Month 16) | 
| Haemophilus Influenzae Type B Antibody Response Rate One Month After Vaccination 4 | Antibody responses to Haemophilus influenzae Type B polyribosylribitol phosphate (Hib PRP) were measured with ELISA. The percentage of participants with anti-HiB PRP antigen ≥0.15 ug/mL are reported. | One month after Vaccination 4 (Month 13 to Month 16) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 3 for 2 Unique V114 Seroptypes | Serotype-specific anti-PnP IgG GMCs for the 2 unique V114 serotypes were measured with PnECL. The GMCs for each serotype are reported. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Response Rates One Month After Vaccination 3 for 2 Unique V114 Seroptypes | Serotype-specific anti-PnP IgG response rates for the 2 unique V114 serotypes were measured with PnECL. The percentage of participants with IgG Ab ≥0.35 ug/mL are reported for each serotype. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMC) One Month After Vaccination 4 for 2 Unique V114 Seroptypes | Serotype-specific anti-PnP GMCs were measured with PnECL. The GMC for each serotype is reported. | One month after Vaccination 4 (Month 13 to Month 16) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) One Month After Vaccination 3 | Serotype-specific anti-PnP OPA GMTs were measured with multiplex opsonophagocytic assay (MOPA). The GMTs for each serotype are summarized. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype-Specific Opsonophagocytic Activity (OPA) Response Rates One Month After Vaccination 3 | Serotype-specific anti-PnP OPA GMTs were measured with MOPA. The percentage of participants meeting ≥0.35 ug/mL are reported for each serotype. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Response Rate One Month After Vaccination 3 | Serotype 3-specific anti-PnP IgG response rates were measured with PnECL. The percentage of participants with IgG Ab ≥0.35 ug/mL are reported for Serotype 3. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 3 | Serotype 3-specific anti-PnP GMC was measured with PnECL. | One month after Vaccination 3 (Month 7) | 
| Anti-Pneumococcal Polysaccharide (Anti-PnP) Serotype 3-Specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) One Month After Vaccination 4 | Serotype 3-specific anti-PnP GMC were measured with PnECL. | One month after Vaccination 4 (Month 13 to Month 16) |