Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 4, and 11 to 12 Months (V419-008)

NCT01480258 | Completed Phase 3 Results

• 2 other identifiers: V419-0082010-021491-28
• Study Type: interventional
• Target: 1,315
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will determine whether participants who receive V419 (PR5I) at 2, 4, and 11 to 12 months of age have an acceptable response to the vaccine. This study will also determine whether the immune response to V419 is similar to that of participants who received a licensed vaccine control. The primary hypothesis is that participants who receive PR5I at 2, 4, and 11 to 12 months have an acceptable response rate to all PR5I-contained antigens at one month after the Toddler dose of PR5I.

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 (1)

• Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age)

  Acceptability response rates were defined as Ab titre ≥1.0 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥10 mIU/mL for Hepatitis (HBsAg); ≥0.1 IU/mL for diphtheria and tetanus; ≥8 (1/dil) for inactive poliovirus type (IPV) 1, 2 \& 3, and percentage of pertussis seroresponder participants (Pertussis toxoid \[PT\], Filamentous haemagglutinin \[FHA\], Fimbriae types 2 \& 3 \[FIM\] and Pertactin \[PRN\]) 1 month Post-Toddler dose of PR5I. Seroresponse was defined: (1) If pre-Dose 1 Ab concentration (cc) was \<LLOQ (lower limit of quantitation), postvaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, postvaccination Ab cc was ≥prevaccination levels. Due to the timing of the occurrence of protocol violation or the availability of each antigen serology testing result, the analysis populations may not have been identical for each antigen-specific analysis at each post-vaccination visit.

  1 month after Toddler dose of PR51 (post-toddler dose)

Secondary Outcomes (8)

• Non-inferiority of Antibody (Ab) Response Rate to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa

  1 month after the 2nd dose (post-infant dose 2)

• Superiority of Antibody (Ab) Response Rates to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa

  1 month after the 2nd dose (post-infant dose 2)

• Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa

  1 month after Toddler dose (post-toddler dose)

• Non-inferiority of Rotavirus Response (Geometric Mean Titer, GMT) One Month After the 2nd Dose of Rotarix (4 Months of Age) Administered Concomitantly With PR5I Versus INFANRIX Hexa

  1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2)

• Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination

  Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination)

Study Arms (2)

PR5I

EXPERIMENTAL

Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Biological: PR5I; Biological: Rotavirus vaccine; Biological: Prevenar 13™

INFANRIX™ hexa

ACTIVE COMPARATOR

Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age \[subset 1\] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age \[subset 2\]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Biological: Rotavirus vaccine; Biological: Prevenar 13™; Biological: INFANRIX™ hexa

Interventions

PR5I BIOLOGICAL

DTaP-HB-IPV-Hib (Diphtheria, tetanus, pertussis \[acellular, component\], hepatitis B \[recombinant DNA\], polio virus \[inactivated\], and Haemophilus influenza type b conjugate vaccine \[adsorbed\]) Vaccine 0.5 mL intramuscular injection at 2, 4, and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. PR5I is a liquid suspension hexavalent vaccine.

Also known as: V419, Vaxelis®

PR5I

Rotavirus vaccine BIOLOGICAL

Rotarix™ 1.5 mL oral dose at 2 and 4 months of age (subset 1, Italy and Sweden) or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age (subset 2, Finland)

INFANRIX™ hexa; PR5I

Prevenar 13™ BIOLOGICAL

Prevenar 13™ 0.5 mL intramuscular injection at 2, 4, and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine.

INFANRIX™ hexa; PR5I

INFANRIX™ hexa BIOLOGICAL

Combined Diphtheria-Tetanus-acellular Pertussis \[DTaP\], Hepatitis B \[HepB\], Poliovirus \[IPV\] and Haemophilus influenzae type b \[Hib\] Vaccine 0.5 mL intramuscular injection at 2, 4 and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. INFANRIX™ hexa is provided as 2 components (lyophilized Hib and liquid DTaP, IPV, and HepB). Prior to administration, the vaccine must be reconstituted by adding the liquid DTaP-HepB-IPV component to the vial containing the Hib pellet.

INFANRIX™ hexa

Eligibility Criteria

• Age: 46 Days - 89 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infant able to attend all study visits
• Parent(s)/legal representative are 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 study entry
• Vaccinated with any acellular pertussis or whole cell pertussis based combination vaccines, Haemophilus influenzae type b conjugate, poliovirus, pneumococcal conjugate or pneumococcal polysaccharide, rotavirus vaccine, or 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 enrolment
• Has a coagulation disorder
• Has developmental delay or neurological disorder
• Participant or his/her mother has a medical history of hepatitis B surface antigens (HBsAg) seropositivity
• History of Haemophilus influenzae type b, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus gastroenteritis, or invasive pneumococcal infection

Sponsors & Collaborators

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

Related Publications (1)

• Silfverdal SA, Icardi G, Vesikari T, 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 2, 4, and 11-12 months. Vaccine. 2016 Jul 19;34(33):3810-6. doi: 10.1016/j.vaccine.2016.05.054. Epub 2016 Jun 18.

  PMID: 27288217 DERIVED

MeSH Terms

Conditions

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

Interventions

Vaxelis; Rotavirus Vaccines; 13-valent pneumococcal 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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2011
• First Posted: November 28, 2011
• Study Start: November 23, 2011
• Primary Completion: October 9, 2013
• Study Completion: October 9, 2013
• Last Updated: April 2, 2019
• Results First Posted: April 2, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share