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

Phase 3

Completed

• Conditions: Bacterial Infections; Virus Diseases
• Interventions: Biological: PR5I; Biological: Rotavirus vaccine; Biological: Prevenar 13™; Biological: INFANRIX™ hexa

• Registration Number: NCT01480258
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-23
• Study First Submitted: 2011-11-23
• Study First Submitted QC: 2011-11-23
• Study First Posted: 2011-11-28
• Primary Completion: 2013-10-09
• Study Completion: 2013-10-09
• Status Verified: 2019-03
• Results First Submitted: 2019-03-11
• Results First Submitted QC: 2019-03-11
• Last Update Submitted: 2019-03-11
• Results First Posted: 2019-04-02
• Last Update Posted: 2019-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1315

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PR5I	Rotavirus vaccine	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.
INFANRIX™ hexa	Rotavirus vaccine	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.
INFANRIX™ hexa	Prevenar 13™	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.
PR5I	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.
PR5I	Prevenar 13™	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.
INFANRIX™ hexa	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.

Primary Outcome Measures

Name	Time	Method
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)	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

Name	Time	Method
Percentage of Participants Reporting Unsolicited ISRs From D1 to D15 After Any Vaccination	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.
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)	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.
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)	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.
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)	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.
Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination	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.
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)	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.
Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination	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.
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)	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.