A Study of V419 Given Concomitantly With Prevnar 13™ and RotaTeq™ (V419-006)

Study Overview
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Brief Summary
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This study will determine whether three manufacturing lots of V419 (PR5I) induce similar immune responses to all of the antigens contained in V419 when given concomitantly with Prevnar13™ and RotaTeq™.

Detailed Description
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This study is partially Double-Blinded in that the participants' parents/guardians, investigator/study site personnel, and Sponsor's representatives will be blinded to the lot of V419 the participant is randomized to receive, but not to the participant's treatment group (V419 or control).

Official Title
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A Phase III Randomized, Partially Double-Blind, Active-Comparator-Controlled, Lot-to-Lot Consistency Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 6 Months Concomitantly With Prevnar 13™ and RotaTeq ™

Conditions
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Bacterial Infections, Virus Diseases

Intervention / Treatment
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* Biological: V419
* Biological: PENTACEL™
* Biological: Prevnar 13™
* Biological: RotaTeq™
* Biological: Recombivax HB vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Participant is a healthy infant Participant has received one dose of monovalent hepatitis B vaccine prior to 1 month of age Exclusion Criteria : Participant has received more than one dose of monovalent hepatitis B vaccine or hepatitis B based combination vaccine prior to study entry Participant has been vaccinated with any acellular pertussis or whole cell pertussis based combination vaccines, haemophilus influenzae type b conjugate, poliovirus, pneumococcal conjugate or pneumococcal polysaccharide, rotavirus, measles, mumps, rubella, or varicella vaccines or any combination of the above Participant has had an illness with fever within 24 hours of study enrollment Participant was vaccinated with any non-study vaccine (i.e. inactivated, conjugated or live virus vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 15 days or more prior to enrollment Participant or his/her mother has hepatitis B surface antigen (HBsAg) seropositivity (by medical history) Participant has a history of haemophilus influenzae type B, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus, or pneumococcal infection

Ages Eligible for Study
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Minimum Age: 46 Days
Maximum Age: 89 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V419 Lot A<br>V419 (Lot A) 0.5 mL intramuscular injection (IM) at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age | Biological: V419<br>* V419 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [Meningococcal Outer Membrane Protein Complex], and Hepatitis B [Recombinant] Vaccine) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.<br>Biological: PENTACEL™<br>* PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group<br>Biological: Prevnar 13™<br>* Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age<br>Biological: RotaTeq™<br>* RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age<br>|
| Experimental: V419 Lot B<br>V419 (Lot B) 0.5 mL IM at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age | Biological: V419<br>* V419 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [Meningococcal Outer Membrane Protein Complex], and Hepatitis B [Recombinant] Vaccine) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.<br>Biological: PENTACEL™<br>* PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group<br>Biological: Prevnar 13™<br>* Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age<br>Biological: RotaTeq™<br>* RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age<br>|
| Experimental: V419 Lot C<br>V419 (Lot C) 0.5 mL IM at 2, 4, and 6 months of age; Pentacel™ 0.5 mL IM at 15 month of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; and RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age | Biological: V419<br>* V419 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [Meningococcal Outer Membrane Protein Complex], and Hepatitis B [Recombinant] Vaccine) (from one of three lots) 0.5 mL intramuscular injection at 2, 4, and 6 months of age.<br>Biological: PENTACEL™<br>* PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group<br>Biological: Prevnar 13™<br>* Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age<br>Biological: RotaTeq™<br>* RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age<br>|
| Active Comparator: Control<br>Pentacel™ 0.5 mL IM at 2, 4, 6, and 15 months of age; Prevnar 13™ 0.5 mL IM at 2, 4, 6, and 15 months of age; RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age; and Recombivax HB vaccine 0.5 mL IM at 2 and 6 months of age | Biological: PENTACEL™<br>* PENTACEL™ 0.5 mL intramuscular injection at 15 months of age in the V419 groups and at 2, 4, 6, and 15 months of age in the control group<br>Biological: Prevnar 13™<br>* Prevnar 13™ 0.5 mL intramuscular injection at 2, 4, 6, and 15 months of age<br>Biological: RotaTeq™<br>* RotaTeq™ 2 mL oral dose at 2, 4, and 6 months of age<br>Biological: Recombivax HB vaccine<br>* Recombivax HB vaccine 0.5 mL intramuscular injection at 2 and 6 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate Antigen | Participant serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate. | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Hepatitis B Surface Antigen | Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. The unit of measure is milli International Units/mL (mIU/mL). | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Diphtheria Toxin | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to diphtheria toxin. The unit of measure is International Units/mL (IU/mL). | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Tetanus Toxin | Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent Assay (ELISA) for anti-tetanus antibodies. | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Pertussis Toxin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. The unit of measure is ELISA units/mL (EU/mL). | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Pertussis Pertactin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Pertussis Fimbriae | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. | Postdose 3 (Month 7) | 
| Geometric Mean Titer for Antibodies to Poliovirus Type 1 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 1. The unit of measure is titer (reciprocal of highest dilution with neutralizing activity). | Postdose 3 (Month 7) | 
| Geometric Mean Titer for Antibodies to Poliovirus Type 2 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 2. | Postdose 3 (Month 7) | 
| Geometric Mean Titer for Antibodies to Poliovirus Type 3 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 3. | Postdose 3 (Month 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Responding to Polyribosylribitol Phosphate Antigen | Participant serum samples were collected for testing with a radioimmunoassay for antibodies to Haemophilus influenza type b capsular polysaccharide polyribosylribitol phosphate. Response was evaluated for a titer >=0.15 µg/mL and >=1.0 µg/mL. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Hepatitis B Surface Antigen | Participant serum samples were collected for testing with an enhanced chemiluminescence assay for antibodies to Hepatitis B Surface Antigen. Response was defined as a titer >=10 mIU/mL. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Diphtheria Toxin | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to diphtheria toxin. Response was defined as a titer >=0.1 IU/mL. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Tetanus Toxin | Participant serum samples were collected for testing with an ELISA for anti-tetanus antibodies. Response was defined as a titer >=0.1 IU/mL. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Pertussis Toxin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Response was defined as follows: 1) if the predose titer was <4 times the lower limit of quantitation (4X LLOQ) then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Pertussis Pertactin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Pertussis Fimbriae | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Poliovirus Type 1 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 1. Response is defined as a titer >=8. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Poliovirus Type 2 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 2. Response is defined as a titer >=8. | Postdose 3 (Month 7) | 
| Percentage of Participants Responding to Poliovirus Type 3 | Participant serum samples were collected for testing with a Micrometabolic Inhibition Test for neutralizing antibodies to Poliovirus Type 3. Response is defined as a titer >=8. | Postdose 3 (Month 7) | 
| Geometric Mean Concentration of Antibodies to Pertussis Toxin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Geometric Mean Concentration of Antibodies to Pertussis Filamentous Hemagglutinin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Geometric Mean Concentration of Antibodies to Pertussis Pertactin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Geometric Mean Concentration of Antibodies to Pertussis Fimbriae | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Percentage of Participants Responding to Pertussis Toxin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Percentage of Participants Responding to Pertussis Filamentous Hemagglutinin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis filamentous hemagglutinin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Percentage of Participants Responding to Pertussis Pertactin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis pertactin. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Percentage of Participants Responding to Pertussis Fimbriae | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis fimbriae. Response was defined as follows: 1) if the predose titer was <4X LLOQ then the postdose titer was >=4X LLOQ; 2) if the predose titer was >=4X LLOQ then the postdose titer was >= the predose titer. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 4 (Month 16) | 
| Geometric Mean Concentration of Antibodies to Pneumococcal Serotypes | Participant serum samples were collected for testing with a multiplex electrochemiluminescence-based detection assay for serotype-specific pneumococcal polysaccharide antibodies. Analysis for this outcome included only non-inferiority of V419 Lots A, B, and C Combined versus Control. | Postdose 3 (Month 7) | 
| Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions | Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Solicited injection site reaction: Pain, Cries when injected limb is moved or the movement of the injected limb is reduced; Erythema and Swelling, >5 cm. Grade 3 Solicited systemic reactions: Fever (Pyrexia), >=39.5°C rectal; Vomiting, >=6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Drowsiness (Somnolence), Sleeping most of the time or difficult to wake up; Appetite lost, Refuses >=3 feeds or refuses most feeds; Irritability, Inconsolable. | Up to 5 days after any infant vaccination (up to 6 months) | 
| Percentage of Participants With Elevated Temperature by Severity | Maximum temperature (all routes) was based on actual temperatures recorded with no adjustments to the measurement route. Maximum temperature (rectal) was required of all participants if the reading by another method was >=38.0°C. | Up to 5 days after any infant vaccination (up to 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tetanus, Diphtheria, Whooping Cough (pertussis), Poliomyelitis, Hepatitis B infection, Haemophilus influenzae type b infection