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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III Open-label Randomised Study, to Evaluate the Immunogenicity and Safety of the Concomitant Administration of V419 (PR5I) Given at 2, 3 and 4 Months of Age With Two Types of Meningococcal Serogroup C Conjugate (MCC) Vaccines Given at 3 and 4 Months of Age, and Followed by the Administration at 12 Months of Age of a Combined Haemophilus Influenzae Type b-MCC Vaccine

Conditions
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Neisseria Meningitidis, Bacterial Infections, Virus Diseases

Intervention / Treatment
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* Biological: V419
* Biological: PREVNAR 13®
* Biological: MCC-TT
* Biological: MCC-CRM
* Biological: Hib-MCC
* Biological: MMR Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 46 Days
Maximum Age: 74 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V419 and MCC-TT<br>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). | Biological: V419<br>* Diphtheria and Tetanus toxoids and acellular Pertussis adsorbed, inactivated Poliovirus, Haemophilus b conjugate [meningococcal outer membrane protein complex], and Hepatitis B [recombinant] vaccine administered via 0.5 mL intramuscular injection.<br>* Other names: PR51, VAXELIS®;Biological: PREVNAR 13®<br>* Pneumococcal conjugate vaccine (13-valent, adsorbed) administered via 0.5 mL intramuscular injection (routine vaccination).<br>Biological: MCC-TT<br>* Meningococcal Group C polysaccharide conjugate vaccine to tetanus toxoid adsorbed 0.5 mL intramuscular injection at 3 and 4 months of age<br>* Other names: NEISVAC-C®;Biological: Hib-MCC<br>* Haemophilus type b and meningococcal Group C conjugate vaccine administered via 0.5 mL intramuscular injection.<br>* Other names: MENITORIX®;Biological: MMR Vaccine<br>* Measles, mumps, and rubella vaccine (live) given via 0.5 mL intramuscular injection (routine vaccination).<br>* Other names: M-M-RVAXPRO®;|
| Experimental: V419 and MCC-CRM<br>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). | Biological: V419<br>* Diphtheria and Tetanus toxoids and acellular Pertussis adsorbed, inactivated Poliovirus, Haemophilus b conjugate [meningococcal outer membrane protein complex], and Hepatitis B [recombinant] vaccine administered via 0.5 mL intramuscular injection.<br>* Other names: PR51, VAXELIS®;Biological: PREVNAR 13®<br>* Pneumococcal conjugate vaccine (13-valent, adsorbed) administered via 0.5 mL intramuscular injection (routine vaccination).<br>Biological: MCC-CRM<br>* Meningococcal Group C conjugate vaccine to CRM-197 adsorbed 0.5 mL intramuscular injection at 3 and 4 months of age<br>* Other names: MENJUGATE®;Biological: Hib-MCC<br>* Haemophilus type b and meningococcal Group C conjugate vaccine administered via 0.5 mL intramuscular injection.<br>* Other names: MENITORIX®;Biological: MMR Vaccine<br>* Measles, mumps, and rubella vaccine (live) given via 0.5 mL intramuscular injection (routine vaccination).<br>* Other names: M-M-RVAXPRO®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | Month 5 (1 month after MCC-TT/MCC-CRM Dose 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Anti-Polyribosylribitol Phosphate (Anti-PRP) Antibody (Ab) Titre ≥0.15 µg/mL One Month After V419 Dose 3 (Part 1) | 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). | Month 5 (1 month after V419 Dose 3) | 
| 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) | 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. | Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2) | 
| Geometric Mean Titres (GMTs) for Meningococcal Serogroup C (MCC) One Month After MCC-TT or MCC-CRM Doses 1 and 2 (Part 1) | 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. | Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2) | 
| Antibody (Ab) Response Rates for V114 Antigens One Month After V114 Dose 3 (Part 1) | 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. | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Haemophilus Influenza Type B (Polyribosylribitol Phosphate [PRP]) One Month After V114 Dose 3 (Part 2) | The GMTs for PRP Ab titres were determined for each arm. Antibody titres for PRP were measured by radioimmunoassay (RIA). | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Hepatitis B Surface Antigen (HBsAg) One Month After V114 Dose 3 (Part 2) | The GMTs for HBsAg Ab titres were determined for each arm. Antibody titres for HBsAg were measured by enhanced chemiluminescence (ECi) assay. | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Diptheria One Month After V114 Dose 3 (Part 2) | The GMTs for diphtheria Ab titres were determined for each arm. Antibody titres for diptheria were measured by enhanced micrometabolic inhibition test (MIT). | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Tetanus One Month After V114 Dose 3 (Part 2) | The GMTs for tetanus Ab titres were determined for each arm. Antibody titres for tetanus were determined with enzyme-linked immunosorbent assay (ELISA). | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Pertussis Toxoid (PT) One Month After V114 Dose 3 (Part 2) | The GMTs for PT Ab titres were determined for each arm. Antibody titres for PT were measured with enzyme-linked immunosorbent assay (ELISA). | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Filamentous Haemagglutinin (FHA) One Month After V114 Dose 3 (Part 2) | The GMTs for FHA were determined for each arm. Antibody titres for FHA were measured by enhanced chemiluminescence (ECi) assay. | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Pertactin (PRN) One Month After V114 Dose 3 (Part 2) | The GMTs for PRN were determined for each arm. Antibody titres for PRN were measured by enhanced chemiluminescence (ECi) assay. | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Fimbrae Types 2 and 3 (FIM) One Month After V114 Dose 3 (Part 2) | The GMTs for FIM were determined for each arm. Antibody titres for FIM were measured by enhanced chemiluminescence (ECi) assay. | Month 5 (1 month after V419 Dose 3) | 
| Antibody (Ab) Geometic Mean Titres (GMTs) for Polio Types 1, 2, and 3 One Month After V114 Dose 3 (Part 2) | 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). | Month 5 (1 month after V419 Dose 3) | 
| 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) | 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. | Month 12 and Month 13 (Prior to anti-Hib MCC and 1 month after anti-HiB MCC) | 
| 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) | 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. | Month 12 and Month 13 (Prior to anti-Hib MCC and 1 month after anti-HiB MCC) | 
| 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) | 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). | Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2) | 
| Geometric Mean Titres (GMTs) for Anti-Polyribosylribitol Phosphate (PRP) Antibody (Ab) One Month After Anti-Haemophilus Influenzae Type B (HiB) MCC Vaccination (Part 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.. | Month 4 and Month 5 (1 month after MCC-TT/MCC-CRM Doses 1 and 2) | 
| Percentage of Participants Experiencing an Adverse Event (AE) [Part 1] | 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. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing an Injection Site (Vaccine-Related) Systemic Adverse Event (AE) [Part 1] | 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. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing a Solicited Injection Site Reaction (ISR) at the V419 Injection Site (Part 1) | The percentage of participants with solicited ISRs was determined for each arm. Solicited ISRs consisted of injection site pain, erythema, and swelling. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) at the V419 Injection Site (Part 1) | The percentage of participants with unsolicited ISRs was determined for each arm. Unsolicited ISRs were any injection-site ISRs not considered solicited. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing a Solicited Injection Site Reaction (ISR) at the MCC-TT or MCC-CRM Injection Site (Part 1) | The percentage of participants with solicited ISRs was determined for each arm. Solicited ISRs consisted of injection site pain, erythema, and swelling. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) at the MCC-TT or MCC-CRM Injection Site (Part 1) | 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. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing a Solicited Systemic Adverse Event (AE) [Part 1] | 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. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing Increased Temperature [Part 1] | The percentage of participants experiencing temperatures ≥38.0° Celsius (C), >38.5° C, and >39.5° C following any Part 1 vaccination was determined. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) | 
| Percentage of Participants Experiencing a Serious Adverse Event (SAE) [Part 1] | 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. | Up to 4.5 months (up to 15 days after the final Part 1 vaccination) |