Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4 and 12 Months (V419-007)

Study Overview
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Brief Summary
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This study will determine whether participants who receive the vaccine V419 at 2, 3, 4, and 12 months of age have an acceptable immune response to the vaccine. The study will also determine whether the immune response to V419 is similar to that of participants who receive a licensed vaccine control.

Official Title
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A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)

Conditions
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Bacterial Infections, Virus Diseases

Intervention / Treatment
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* Biological: V419
* Biological: INFANRIX™ hexa
* Biological: RotaTeq
* Biological: Prevenar 13
* Biological: ProQuad™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Healthy infants able to attend all study visits Parent(s)/legal representative able to read, understand, and complete study questionnaires Exclusion Criteria History of congenital or acquired immunodeficiency Received or is expected to receive immunosuppressive agents or systemic immunomodulatory steroids History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder Hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or concomitant study vaccines Has any chronic illness that could interfere with study conduct or completion Received any immune globulin, blood, or blood-derived products since birth Received a dose of hepatitis B vaccine prior to the study 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 thereof Fever within 24 hours prior to enrollment Received any non-study vaccine within 30 days prior to enrollment, except for inactivated influenza vaccine, which is permitted 14 days or more prior to enrollment Has a coagulation disorder Has developmental delay or neurological disorder Participant or his/her mother has a medical history of hepatitis B surface antigen (HBsAg) seropositivity History of measles, mumps, rubella, varicella, Haemophilus influenzae type B, hepatitis B, diphtheria, tetanus, pertussis, rotavirus, invasive pneumococcal, or poliomyelitis infection

Ages Eligible for Study
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Minimum Age: 46 Days
Maximum Age: 74 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PR5I<br>V419 + RotaTeq + Prevenar 13 + ProQuad | 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, 3, 4, and 12 months of age.<br>Biological: RotaTeq<br>* RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age<br>Biological: Prevenar 13<br>* Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age<br>Biological: ProQuad™<br>* ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age<br>|
| Active Comparator: INFANRIX™ hexa<br>INFANRIX™ hexa + RotaTeq + Prevenar 13 + ProQuad | Biological: INFANRIX™ hexa<br>* INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.<br>Biological: RotaTeq<br>* RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age<br>Biological: Prevenar 13<br>* Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age<br>Biological: ProQuad™<br>* ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 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 Vaccinated With PR5I With Acceptable Antibody (Ab) Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months | Antibody titres in the PR5I group were measured by Radioimmunoassay (RIA) for Haemophilus influenzae type b (PRP), Micrometabolic inhibition test (MIT) for diphtheria & poliovirus, and Enzyme-Linked Immunosorbent Assay (ELISA) for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits for PRP, diphtheria (80%), tetanus (90%), and IPV1, 2 & 3 (90%). | One month after post-dose 3 of PRI5 (5 months old) | 
| Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response or Seroresponse Rates to All Antigens Contained in the PR5I Vaccine One Month After the Toddler Dose at 13 Months | Antibody titres in the PR5I group were measured by RIA for PRP, MIT for diphtheria & poliovirus, enhanced Chemiluminescence assay (ECi)) for Hepatitis B surface antigen (HBsAg) and ELISA for tetanus, Pertussis toxoid (PT), Filamentous haemagglutinin (FHA), Fimbriae types 2 & 3 (FIM) & Pertactin (PRN). Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (PRP); ≥0.1 IU/mL; for diphtheria & tetanus; ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, FIM and PRN are reported. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the lower CI limits for PRP, PT, FHA, FIM, and PRN (75%); Diphtheria (80%); HBsAG, IPV 1, 2, 3 (90%). | One month after Toddler dose of PRI5 (13 months old) | 
| Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Haemophilus Influenzae Type b, Diphtheria, Tetanus, and Poliovirus Types 1, 2 & 3, at 5 Months | Antibody titres were measured by RIA for PRP, MIT for diphtheria & poliovirus, and ELISA for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Hib) (PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country. | One month after post-dose 3 of PRI5 (5 months old) | 
| Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response Rates to Hepatitis B and Seroresponse to Pertussis Antigens Pt, FHA and PRN One Month After the Toddler Dose at 13 Months Old | Antibody titres were measured by ECi for HBsAg and ELISA for PT, FHA, & PRN. Percentage of participants with an Ab titre ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, and PRN are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country. | One month after Toddler dose of PRI5 (13 months old) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Vaccinated With PR5I With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old | Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. 95% CI were calculated based on the exact binomial method by Clopper and Pearson. The immune response to ProQuad vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits: 90% for measles, mumps & rubella, and 76% for varicella. | One month after Toddler dose of PRI5 (13 months old) | 
| Percentage of Participants Vaccinated With PR5I Compared With INFANRIX™ Hexa With Acceptable Ab Response to Measles, Mumps, Rubella and Varicella One Month After the Toddler Dose of ProQuad at 13 Months Old | Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country. | One month after Toddler dose of PRI5 (13 months old) | 
| Percentage of Participants With Injection-site and Systemic Adverse Events (AEs) From Day 1 to Day 15 After Any Vaccination | Global safety was assessed by measuring injection-site and systemic AEs reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 to Day 15 (D1-D15) after each hexavalent vaccination. Solicited injection-site and systemic AEs were reported daily from Day 1 to Day 5 (D1-D5) after each hexavalent vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). The investigator assessed whether systemic AEs were related (V-related) or not to the vaccine. All AEs (related and unrelated) are reported. | Day 1 to Day 15 after any vaccination | 
| Percentage of Participants Reporting Solicited ISRs From Day 1 to Day 5 After Any Vaccination | Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from Day 1 (D1) to Day 5 (D5) after vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). | Day 1 to Day 5 after any vaccination | 
| Percentage of Participants Reporting Unsolicited ISRs From Day 1 to Day 15 After Any Vaccination | Unsolicited ISRs with incidence ≥1% after any vaccination were reported daily on the VRC by the parent(s) or legal representative from (D1-D15). AEs at injection sites were always considered as vaccine-related ISRs | Day 1 to Day 15 after any vaccination | 
| Percentage of Participants Reporting Solicited Systemic AE From Day 1 to Day 5 After Any Vaccination | Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator assessed whether these systemic AEs were related or not to the vaccines. All (related and unrelated) AEs are reported. | Day 1 to Day 5 after any vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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combination vaccine, diphtheria, pertussis, tetanus, hepatitis B, Hep B, Haemophilus influenzae b, Hib, polio, poliovirus