Immunogenicity and Safety of V419 (PR51) in Combination With MCC in Infants and Toddlers (V419-011)

Phase 3

Completed

Conditions: Neisseria Meningitidis
Bacterial Infections
Virus Diseases

Interventions: Biological: V419
Biological: PREVNAR 13®
Biological: MCC-TT
Biological: MCC-CRM
Biological: Hib-MCC
Biological: MMR Vaccine

Registration Number: NCT01553279

Lead Sponsor: MCM Vaccines B.V.

Brief Summary: The primary objectives of this study are to evaluate the immunogenicity and safety of concomitant administration of V419 (PR51) with 2 types of meningococcal serogroup C conjugate (MCC) vaccines to healthy infants at 3 and 4 months of age in terms of antibody seroprotection rate (SPR) to MCC. Participants also received a Haemophilus influenza type B (Hib)-MCC vaccination at 12 months of age. It was hypothesized that the SPR to MCC at 1 month post-dose 2 of either tetanus toxoid conjugated Meningo C (MCC-TT) or CRM197 conjugated Meningo C (MCC-CRM) vaccines would be acceptable when administered concomitantly with V419.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 284

Inclusion Criteria

Healthy infant 46 to 74 days of age (both inclusive)
Parent(s)/legal representative able to comply will the study procedures

Exclusion Criteria

Is participating in a study with an investigational compound or device since birth
Has a history of congenital or acquired immunodeficiency
Has a history of leukemia, lymphoma, malignant melanoma or myeloproliferative disorder
Has a chronic illness that could interfere with study conduct or completion
Has hypersensitivity to any of the vaccines components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines or contraindication to any of the study vaccines
Has a history, or mother has a history, of hepatitis B virus surface antigen (HBsAg) seropositivity
Has a coagulation disorder that contraindicate intramuscular injection
Has a history of vaccination with a hepatitis B, Haemophilus influenzae type b conjugate, diphtheria, tetanus, pertussis (acellular or whole-cell), poliovirus, pneumococcal conjugate or polysaccharide, meningococcal serogroup C conjugate, measles, mumps, or rubella containing vaccine(s)
Has a history of hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, poliomyelitis, invasive pneumococcal, meningococcal serogroup C, measles, mumps or rubella infection
Has received immune globulin, blood or blood-derived products, immunosuppressive agents systemic corticosteroids since birth
Has received vaccination with an inactivated (except influenza vaccine) or conjugated or live vaccine in the last 30 days or vaccination with an inactivated influenza vaccine in the last 14 days
Has received antipyretic, analgesic and non-steroidal anti-inflammatory medications in the last 48 hours
Has a febrile illness or body temperature ≥38.0°C in the last 24 hours

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
V419 and MCC-CRM	V419	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-CRM (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of an MMR vaccine (at 12 months of age).
V419 and MCC-CRM	PREVNAR 13®	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-CRM (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of an MMR vaccine (at 12 months of age).
V419 and MCC-CRM	Hib-MCC	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-CRM (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of an MMR vaccine (at 12 months of age).
V419 and MCC-CRM	MMR Vaccine	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-CRM (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of an MMR vaccine (at 12 months of age).
V419 and MCC-TT	PREVNAR 13®	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-TT (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of a measles, mumps, and rubella (MMR) vaccine (at 12 months of age).
V419 and MCC-TT	MMR Vaccine	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-TT (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of a measles, mumps, and rubella (MMR) vaccine (at 12 months of age).
V419 and MCC-TT	V419	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-TT (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of a measles, mumps, and rubella (MMR) vaccine (at 12 months of age).
V419 and MCC-TT	MCC-TT	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-TT (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of a measles, mumps, and rubella (MMR) vaccine (at 12 months of age).
V419 and MCC-TT	Hib-MCC	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-TT (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of a measles, mumps, and rubella (MMR) vaccine (at 12 months of age).
V419 and MCC-CRM	MCC-CRM	Participants received 3 doses of V419 (at 2, 3, and 4 months of age) and 2 doses of MCC-CRM (at 3 and 4 months of age), followed by a single dose of Hib-MCC at 12 months of age. As routine vaccination, participants also received 2 doses of Prevnar 13® (at 2 and 4 months of age) and 1 dose of an MMR vaccine (at 12 months of age).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Anti-Meningococcal Serogroup C (Anti-MCC) Antibody (Ab) Titre ≥1:8 Dil One Month After MCC-TT or MCC-CRM (Part 1)	Month 5 (1 month after MCC-TT/MCC-CRM Dose 2)	The acceptability (i.e., percentage of participants with anti-MCC Ab titre ≥1:8 dil) of the seroprotection rate (SPR) to MCC was determined 1 month after MCC-TT or MCC-CRM Dose 2. The SPR was considered acceptable if the lower bound of the 2-sided 95% CI was \>90%. Serum Ab levels were assayed using the Meningo C rabbit complement serum bactericidal Ab (rSBA) assay.

Secondary Outcome Measures

Name	Time	Method
Antibody (Ab) Geometic Mean Titres (GMTs) for Pertussis Toxoid (PT) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for PT Ab titres were determined for each arm. Antibody titres for PT were measured with enzyme-linked immunosorbent assay (ELISA).
Geometric Mean Titres (GMTs) for Meningococcal Serogroup C (MCC) One Month After MCC-TT or MCC-CRM Doses 1 and 2 (Part 1)	Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2)	Anti-MCC antibody GMTs were determined 1 month after MCC-TT or MCC-CRM Doses 1 and 2 in participants also treated with V419. Serum antibody levels were assayed using the Meningo C rabbit complement serum bactericidal antibody (rSBA) assay.
Antibody (Ab) Geometic Mean Titres (GMTs) for Haemophilus Influenza Type B (Polyribosylribitol Phosphate [PRP]) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for PRP Ab titres were determined for each arm. Antibody titres for PRP were measured by radioimmunoassay (RIA).
Antibody (Ab) Geometic Mean Titres (GMTs) for Pertactin (PRN) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for PRN were determined for each arm. Antibody titres for PRN were measured by enhanced chemiluminescence (ECi) assay.
Percentage of Participants With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody (Ab) Titre ≥0.15 µg/mL One Month After V419 Dose 3 (Part 1)	Month 5 (1 month after V419 Dose 3)	The acceptability (i.e., percentage of participants with anti-PRP Ab titre ≥0.15 µg/mL) of the seroprotection rate (SPR) to Haemophilus influenza type b (Hib) was determined 1 month after the third dose of V419 in participants also treated with MCC-TT or MCC-CRM. The pooled (i.e., all V419-treated participants) SPR was considered acceptable if the lower bound of the 2-sided 95% CI was \>80%. Serum Ab levels were determined with radioimmunoassay (RIA).
Percentage of Participants With Anti-Meningococcal Serogroup C (Anti-MCC) Antibody (Ab) Titre ≥1:8 Dil and ≥1:128 Dil One Month After MCC-TT or MCC-CRM Doses 1 and 2 (Part 1)	Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2)	The percentage of participants with anti-MCC Ab titres ≥1:8 dil and ≥1:128 dil 1 month after MCC-TT or MCC-CRM Doses 1 and 2 was determined in participants also treated with V419. Serum Ab levels were assayed using the Meningo C rabbit complement serum bactericidal Ab (rSBA) assay.
Antibody (Ab) Response Rates for V114 Antigens One Month After V114 Dose 3 (Part 1)	Month 5 (1 month after V419 Dose 3)	The percentage of participants meeting Ab response rates for V14 antigens was determined after V114 Dose 3. Antibody response rate criteria for Haemophilus influenza Type B (PRP); hepatitis B (HBsAg); diphtheria; tetanus; and polio types 1, 2, and 3 are shown in the rows below. The percentage of seroresponders to pertussis seroresponders (pertussis toxoid \[PT\]; filamentous haemagglutinin (FHA); fimbrae types 2 and 3 \[FIM\]; and pertactin \[PRN\]) was determined as 1) if pre-vaccination Ab concentration \<lower limit of quantification (LLoQ) but post-vaccination Ab concentration ≥LLoQ; or 2) if pre-vaccination Ab concentration was ≥LLoQ but post-vaccination Ab concentration was ≥pre-immunization levels. Antibody titres were measured by RIA for PRP, enhanced chemiluminescence assay (ECi) for HBsAg, micrometabolic inhibition test (MIT) for diphtheria and poliovirus, and enzyme-linked immunosorbent assay (ELISA) for tetanus, PT, FHA, FIM, and PRN.
Antibody (Ab) Geometic Mean Titres (GMTs) for Polio Types 1, 2, and 3 One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for polio types 1, 2, and 3 were determined for each arm. Antibody titres for polio types 1, 2, and 3 were measured by micrometabolic inhibition test (MIT).
Percentage of Participants With Anti-Polyribosylribitol Phosphate (PRP) Antibody (Ab) Titres ≥0.15 µg/mL and ≥1.0 µg/mL One Month After Anti-Haemophilus Influenzae Type B MCC Vaccination (Part 2)	Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2)	The percentage of participants with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL was determined prior to, and 1 month after, administration of the anti-Hib vaccination at Month 12. Anti-PRP Ab titres were measured with radioimmunoassay (RIA).
Antibody (Ab) Geometic Mean Titres (GMTs) for Hepatitis B Surface Antigen (HBsAg) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for HBsAg Ab titres were determined for each arm. Antibody titres for HBsAg were measured by enhanced chemiluminescence (ECi) assay.
Antibody (Ab) Geometic Mean Titres (GMTs) for Diptheria One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for diphtheria Ab titres were determined for each arm. Antibody titres for diptheria were measured by enhanced micrometabolic inhibition test (MIT).
Antibody (Ab) Geometic Mean Titres (GMTs) for Tetanus One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for tetanus Ab titres were determined for each arm. Antibody titres for tetanus were determined with enzyme-linked immunosorbent assay (ELISA).
Antibody (Ab) Geometic Mean Titres (GMTs) for Filamentous Haemagglutinin (FHA) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for FHA were determined for each arm. Antibody titres for FHA were measured by enhanced chemiluminescence (ECi) assay.
Antibody (Ab) Geometic Mean Titres (GMTs) for Fimbrae Types 2 and 3 (FIM) One Month After V114 Dose 3 (Part 2)	Month 5 (1 month after V419 Dose 3)	The GMTs for FIM were determined for each arm. Antibody titres for FIM were measured by enhanced chemiluminescence (ECi) assay.
Percentage of Participants Experiencing an Injection Site (Vaccine-Related) Systemic Adverse Event (AE) [Part 1]	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product. As per protocol, all injection site AEs were considered vaccine-related.
Percentage of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) at the V419 Injection Site (Part 1)	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants with unsolicited ISRs was determined for each arm. Unsolicited ISRs were any injection-site ISRs not considered solicited.
Percentage of Participants With Anti-Meningococcal Serogroup C (Anti-MCC) Antibody (Ab) Titre ≥1:8(1/Dil) and Titre ≥1:28 (1/Dil) One Month After Anti-Haemophilus Influenzae Type B (Anti-Hib) Vaccination (Part 2)	Month 12 and Month 13 (Prior to anti-Hib MCC and 1 month after anti-HiB MCC)	The percentage of participants with anti-Hib Ab titres ≥1:8 (1/dil) and ≥1:28 (1/dil) were determined prior to, and 1 month after, administration of the single HiB-MCC vaccine at 12 months of age. Serum Ab levels were assayed using the Meningo C rabbit complement serum bactericidal Ab (rSBA) assay.
Percentage of Participants Experiencing a Solicited Injection Site Reaction (ISR) at the V419 Injection Site (Part 1)	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants with solicited ISRs was determined for each arm. Solicited ISRs consisted of injection site pain, erythema, and swelling.
Percentage of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) at the MCC-TT or MCC-CRM Injection Site (Part 1)	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants with unsolicited ISRs was determined for each arm. Unsolicited ISRs consisted of bruising, dermatitis, erythema, induration, mass, pain, rash, and warmth.
Percentage of Participants Experiencing Increased Temperature [Part 1]	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants experiencing temperatures ≥38.0° Celsius (C), \>38.5° C, and \>39.5° C following any Part 1 vaccination was determined.
Antibody (Ab) Geometric Mean Titres (GMTs) for Meningococcal Serogroup C (MCC) One Month After Anti-Haemophilus Influenzae Type B (Anti-Hib) Meningococcal Serogroup C (MCC) Vaccination (Part 2)	Month 12 and Month 13 (Prior to anti-Hib MCC and 1 month after anti-HiB MCC)	Antibody GMTs were were determined prior to, and 1 month after, administration of the single HiB-MCC vaccine at 12 months of age. Serum Ab levels were assayed using the Meningo C rabbit complement serum bactericidal Ab (rSBA) assay.
Geometric Mean Titres (GMTs) for Anti-Polyribosylribitol Phosphate (PRP) Antibody (Ab) One Month After Anti-Haemophilus Influenzae Type B (HiB) MCC Vaccination (Part 2)	Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2)	Anti-PRP Ab GMTs were determined prior to, and 1 month after, administration of the anti-Hib vaccination at Month 12. Anti-PRP Ab titres were measured with radioimmunoassay (RIA) and are expressed as µg/mL..
Percentage of Participants Experiencing an Adverse Event (AE) [Part 1]	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the investigational product, whether or not considered related to the use of the product.
Percentage of Participants Experiencing a Solicited Injection Site Reaction (ISR) at the MCC-TT or MCC-CRM Injection Site (Part 1)	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants with solicited ISRs was determined for each arm. Solicited ISRs consisted of injection site pain, erythema, and swelling.
Percentage of Participants Experiencing a Serious Adverse Event (SAE) [Part 1]	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	An SAE is an event that results in death; is life-threatening; results in or prolongs hospitalization; is a congenital anomaly/birth defect; is a cancer; is an overdose; or is another important medical event that may jeopardize the participant.
Percentage of Participants Experiencing a Solicited Systemic Adverse Event (AE) [Part 1]	Up to 4.5 months (up to 15 days after the final Part 1 vaccination)	The percentage of participants with solicited systemic AEs was determined for each arm. Solicited systemic AEs consisted of crying, decreased appetite, irritability, pyrexia, somnolence, and vomiting.