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

NCT01341639 | Completed Phase 3 Results

• 2 other identifiers: V419-0072010-021490-37
• Study Type: interventional
• Target: 1,250
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Bacterial Infections; Virus Diseases

Keywords

combination vaccine; diphtheria; pertussis; tetanus; hepatitis B; Hep B; Haemophilus influenzae b; Hib; polio; poliovirus

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• 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

  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

  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

  Day 1 to Day 15 after any vaccination

• Percentage of Participants Reporting Solicited ISRs From Day 1 to Day 5 After Any Vaccination

  Day 1 to Day 5 after any vaccination

• Percentage of Participants Reporting Unsolicited ISRs From Day 1 to Day 15 After Any Vaccination

  Day 1 to Day 15 after any vaccination

Study Arms (2)

PR5I

EXPERIMENTAL

V419 + RotaTeq + Prevenar 13 + ProQuad

Biological: V419; Biological: RotaTeq; Biological: Prevenar 13; Biological: ProQuad™

INFANRIX™ hexa

ACTIVE COMPARATOR

INFANRIX™ hexa + RotaTeq + Prevenar 13 + ProQuad

Biological: INFANRIX™ hexa; Biological: RotaTeq; Biological: Prevenar 13; Biological: ProQuad™

Interventions

V419 BIOLOGICAL

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.

PR5I

INFANRIX™ hexa BIOLOGICAL

INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

INFANRIX™ hexa

RotaTeq BIOLOGICAL

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

INFANRIX™ hexa; PR5I

Prevenar 13 BIOLOGICAL

Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age

INFANRIX™ hexa; PR5I

ProQuad™ BIOLOGICAL

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

INFANRIX™ hexa; PR5I

Eligibility Criteria

• Age: 46 Days - 74 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infants able to attend all study visits
• Parent(s)/legal representative able to read, understand, and complete study questionnaires

You may not qualify if:

• 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

Sponsors & Collaborators

• MCM Vaccines B.V.: lead
• Merck Sharp & Dohme LLC: collaborator

Related Publications (1)

• Vesikari T, Becker T, Vertruyen AF, Poschet K, Flores SA, Pagnoni MF, Xu J, Liu GF, Stek JE, Boisnard F, Thomas S, Ziani E, Lee AW. A Phase III Randomized, Double-blind, Clinical Trial of an Investigational Hexavalent Vaccine Given at Two, Three, Four and Twelve Months. Pediatr Infect Dis J. 2017 Feb;36(2):209-215. doi: 10.1097/INF.0000000000001406.

  PMID: 27846055 DERIVED

MeSH Terms

Conditions

Bacterial Infections; Virus Diseases; Diphtheria; Whooping Cough; Tetanus; Hepatitis B; Haemophilus Infections; Poliomyelitis

Interventions

RotaTeq; 13-valent pneumococcal vaccine; measles, mumps, rubella, varicella vaccine

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Clostridium Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Pasteurellaceae Infections; Myelitis; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Neuromuscular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2011
• First Posted: April 26, 2011
• Study Start: May 26, 2011
• Primary Completion: March 13, 2013
• Study Completion: March 13, 2013
• Last Updated: April 30, 2019
• Results First Posted: April 10, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share