Safety, Tolerability, and Immunogenicity of V419 Given Concomitantly With Prevnar 13™ and RotaTeq™ (V419-005)

Study Overview
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Brief Summary
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This is a study to assess the safety, tolerability, and immunogenicity of V419 (PR5I) when administered as an infant series at 2, 4, and 6 months of age followed by a toddler dose of DAPTACEL™, Prevnar 13™ and PedvaxHIB™ at 15 months of age. The study will determine whether subjects who receive V419 have a similar immune response to the vaccine compared to subjects who receive licensed component vaccine controls.

Official Title
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A Phase III Randomized, Open-Label, Active-Comparator Controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V419 in 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: DAPTACEL™
* Biological: PedvaxHIB™
* Biological: Prevnar 13™
* Biological: RotaTeq™
* Biological: PENTACEL™
* Biological: Recombivax HB vaccine
* Biological: ActHIB™


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 or at 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, or any combination of the above Participant has had a fever ≥38.0°C (≥110.4°F) within 24 hours of study enrollment Participant was vaccinated with any non-study vaccine (i.e., inactivated, conjugated, live virus vaccine) within 30 days prior to study enrollment, except for inactivated influenza vaccine which will be permitted 15 days or more prior to enrollment Participant 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V419<br>V419 0.5 mL intramuscular injection (IM) at 2, 4, and 6 months of age; Daptacel™ 0.5 mL IM at 15 months of age; PedvaxHIB™ 0.5 mL IM at 15 months 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) 0.5 mL intramuscular injection at 2, 4, and 6 months of age<br>Biological: DAPTACEL™<br>* DAPTACEL™ 0.5 mL intramuscular injection at 15 months of age<br>Biological: PedvaxHIB™<br>* PedvaxHIB™ 0.5 mL intramuscular injection at 15 months of age<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>* Other names: V260;|
| Active Comparator: Control<br>Pentacel™ 0.5 mL IM at 2, 4, and 6 months of age; Recombivax HB vaccine 0.5 mL IM at 2 and 6 months of age; Daptacel™ 0.5 mL IM at 15 months of age; ActHIB™ 0.5 mL IM at 15 months 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: DAPTACEL™<br>* DAPTACEL™ 0.5 mL intramuscular injection at 15 months of age<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>* Other names: V260;Biological: PENTACEL™<br>* PENTACEL™ 0.5 mL intramuscular injection 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>Biological: ActHIB™<br>* ActHIB™ 0.5 mL intramuscular injection at 15 months of age<br>|

What is the study measuring?
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Primary 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 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 milli International units (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 International unit (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 Enzyme-linked Immunosorbent Assay (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. 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) | 
| 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 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 <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 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 <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 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 <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 4 (Month 16) | 
| Geometric Mean Concentration of Antibodies to Pertussis Toxin | Participant serum samples were collected for testing with an ELISA for antibodies to pertussis toxin. | 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. | 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. | 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. | Postdose 4 (Month 16) | 

Secondary 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 Immunoglobulin A (IgA) Antibodies to Rotavirus | Participant serum samples were collected for testing with an Enzyme-linked Immunosorbent assay for IgA antibodies to rotavirus. | 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: Pyrexia, Vomiting, Crying abnormal, Somnolence, Decreased appetite, 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: Pyrexia, >=39.5°C (>=103.1°F) rectal; Vomiting, >=6 episodes per 24 hours or requiring parenteral hydration; Crying abnormal, >3 hours; Somnolence, Sleeping most of the time or difficult to wake up; Decreased appetite, Refuses >=3 feeds or refuses most feeds; Irritability, Inconsolable. | Up to 5 days after any infant vaccination (up to 6 months) | 
| Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug | Solicited systemic adverse events: pyrexia, vomiting, crying abnormal, somnolence, decreased appetite, and irritability. Adverse events deemed related to study drug were those judged to be definitely related, probably related, or possibly related by the investigator. | Up to 5 days after any infant vaccination (up to 6 months) | 
| Percentage of Participants Reporting One or More Solicited Adverse Events Related to Study Drug | Solicited systemic adverse events: pyrexia, vomiting, crying abnormal, somnolence, decreased appetite, and irritability. Adverse events deemed related to study drug were those judged to be definitely related, probably related, or possibly related by the investigator. | Up to 5 days after each 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) | 
| Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion | The percentage of participants with one or more adverse events (AE), serious adverse events (SAE), and vaccine-related SAE (pyrexia, febrile convulsion, and convulsion) is reported. | Up to 15 days after any infant vaccination (up to 6 months) | 
| Percentage of Participants With Pyrexia, Febrile Convulsion, or Convulsion | The percentage of participants with one or more adverse events (AE), serious adverse events (SAE), and vaccine-related SAE (pyrexia, febrile convulsion, and convulsion) is reported. | Up to 181 days after any infant vaccination (up to 12 months) | 

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