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

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ClinicalTrials.gov Identifier: NCT01480258
Recruitment Status : Completed
First Posted : November 28, 2011
Results First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
MCM Vaccines B.V.

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.

Condition or disease Intervention/treatment Phase
Bacterial Infections Virus Diseases Biological: PR5I Biological: Rotavirus vaccine Biological: Prevenar 13™ Biological: INFANRIX™ hexa Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1315 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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, 4, and 11 to 12 Months
Actual Study Start Date : November 23, 2011
Actual Primary Completion Date : October 9, 2013
Actual Study Completion Date : October 9, 2013


Arm Intervention/treatment
Experimental: PR5I

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
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.
Other Names:
  • V419
  • Vaxelis®

Biological: Rotavirus vaccine
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)

Biological: Prevenar 13™
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.

Active Comparator: INFANRIX™ hexa

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
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)

Biological: Prevenar 13™
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.

Biological: INFANRIX™ hexa
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.




Primary Outcome Measures :
  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) [ Time Frame: 1 month after Toddler dose of PR51 (post-toddler dose) ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 1 month after the 2nd dose (post-infant dose 2) ]
    Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

  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 [ Time Frame: 1 month after the 2nd dose (post-infant dose 2) ]
    Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by RIA 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

  3. 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 [ Time Frame: 1 month after Toddler dose (post-toddler dose) ]
    Percentage of participants with pre-specified Ab titre for PRP, HBsAg, diphtheria, tetanus, IPV1, 2 & 3, and percentage of pertussis seroresponder participants (PT, FHA, FIM and PRN) 1 month post-toddler dose were calculated based on the method by Miettinen and Nurminen stratified by country. Seroresponse was defined: (1) If pre-Dose 1 Ab cc was <LLOQ, post-vaccination Ab cc was ≥LLOQ, (2) If pre-Dose 1 Ab cc was ≥LLOQ, post-vaccination Ab cc was ≥pre-vaccination 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.

  4. 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 [ Time Frame: 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2) ]
    Antibody titres expressed in units/mL were measured for Rotavirus IgA by Enzyme Immunoassay (EIA), 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2). The 95% CI for GMT was based on the t-distribution of the natural log-transformed antibody titer.

  5. Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination [ Time Frame: Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination) ]
    Injection-site and systemic AEs were reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 (D1) to D15 after each vaccination. Solicited injection site and systemic AEs were reported daily from D1 to D5 after each vaccination. AEs at injection sites were always considered as vaccine-related (V-related) (Injection-Site Reactions [ISRs]). The investigator had to assess whether systemic AEs were related or not to the vaccine. All AEs (related and unrelated) are displayed here.

  6. Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination [ Time Frame: Up to 5 days (Day 1 to Day 5 following vaccination) ]
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions [ISRs]). Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from D1 to D5 after vaccination.

  7. Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination [ Time Frame: From D1 to D15 after any vaccination ]
    Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions {ISRs]). Unsolicited ISRs occurring from Day 1 (D1) to D15 after any vaccination were reported daily on the VRC by the parent(s) or legal representative. Unsolicited ISRs with incidence ≥1% are reported below.

  8. Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination [ Time Frame: Up to 5 days (from D1 to D5 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 had to assess whether these systemic AEs were related or not to the vaccines. All (related and unrelated) are displayed here.



Information from the National Library of Medicine

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Ages Eligible for Study:   46 Days to 89 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy infant able to attend all study visits
  • Parent(s)/legal representative are 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01480258


Sponsors and Collaborators
MCM Vaccines B.V.
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: MCM Vaccines B.V.
ClinicalTrials.gov Identifier: NCT01480258     History of Changes
Other Study ID Numbers: V419-008
2010-021491-28 ( EudraCT Number )
V419-008 ( Other Identifier: Merck )
First Posted: November 28, 2011    Key Record Dates
Results First Posted: April 2, 2019
Last Update Posted: April 2, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by MCM Vaccines B.V.:
combination vaccine
diphtheria
pertussis
tetanus
hepatitis B
Hep B
Haemophilus influenzae b
Hib
polio
poliovirus

Additional relevant MeSH terms:
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Bacterial Infections
Virus Diseases
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs