Study to Evaluate the Safety and Immunogenicity of a Multivalent Pneumococcal Vaccine Given With Prevnar 13 in Healthy Infants

Study Overview
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Brief Summary
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This is a Phase 2, randomized, active-controlled, open-label study with a 3-arm parallel design. Healthy 2-month old infants (42 to 98 days of age) with no history of pneumococcal vaccination will be randomized in a 1:1:1 ratio to receive a 4-dose series of: multivalent pneumococcal conjugate vaccine coadministered with Prevnar 13 (Group 1); multivalent pneumococcal conjugate vaccine given 1 month after Prevnar 13 (Group 2); or Prevnar 13 with a single dose of multivalent pneumococcal conjugate vaccine (Group 3).

Official Title
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A PHASE 2, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A MULTIVALENT PNEUMOCOCCAL CONJUGATE VACCINE GIVEN WITH, OR SEPARATELY FROM, 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: Multivalent
* Biological: Prevnar 13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female infant born at >36 weeks of gestation and aged 2 months (42 to 98 days) at the time of consent (the day of birth is considered day of life 1). Healthy infant determined by medical history, physical examination, and clinical judgment. Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal vaccine. Prior receipt of routine pediatric vaccines, with the exception of hepatitis B vaccine. Previous receipt of >1 dose of hepatitis B vaccine. Prior hepatitis B vaccine must have been administered at age <30 days. Major known congenital malformation or serious chronic disorder. Receipt of blood/plasma products or immunoglobulins.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 98 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: Group 1 - Coadministration<br>Multivalent pneumococcal conjugate vaccine coadministered with Prevnar 13 | Biological: Multivalent<br>* Pneumococcal conjugate vaccine<br>* Other names: Pneumococcal conjugate vaccine;Biological: Prevnar 13<br>* Pneumococcal conjugate vaccine<br>|
| Experimental: Group 2 - Staggered Administration<br>Multivalent pneumococcal conjugate vaccine given 1 month after Prevnar 13 | Biological: Multivalent<br>* Pneumococcal conjugate vaccine<br>* Other names: Pneumococcal conjugate vaccine;Biological: Prevnar 13<br>* Pneumococcal conjugate vaccine<br>|
| Active Comparator: Group 3 - Control with Supplemental Dose<br>Prevnar 13 with a single dose of multivalent pneumococcal conjugate vaccine | Biological: Multivalent<br>* Pneumococcal conjugate vaccine<br>* Other names: Pneumococcal conjugate vaccine;Biological: Prevnar 13<br>* Pneumococcal conjugate vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions Within 7 Days After Dose 1 | Local reactions were recorded using an electronic diary (e-diary) by participant's legally acceptable representative (LAR). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 0.0 to 2.0 cm), moderate (>2.0 to 7.0 cm) and severe (>7 cm). Pain at injection site was graded as mild (hurt if gently touched), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). | Within 7 Days After Dose 1 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 2 | Local reactions were recorded using an electronic diary by participant's LAR. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0.0 to 2.0 cm), moderate (>2.0 to 7.0 cm) and severe (>7 cm). Pain at injection site was graded as mild (hurt if gently touched), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). | Within 7 Days After Dose 2 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 3 | Local reactions were recorded using an electronic diary by participant's LAR. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0.0 to 2.0 cm), moderate (>2.0 to 7.0 cm) and severe (>7 cm). Pain at injection site was graded as mild (hurt if gently touched), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). | Within 7 Days After Dose 3 | 
| Percentage of Participants With Local Reactions Within 7 Days After Dose 4 | Local reactions were recorded using an electronic diary by participant's LAR. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0.0 to 2.0 cm), moderate (>2.0 to 7.0 cm) and severe (>7 cm). Pain at injection site was graded as mild (hurt if gently touched), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). | Within 7 Days After Dose 4 | 
| Percentage of Participants With Local Reactions Within 7 Days After Supplemental Dose (SD) | Local reactions were recorded using an electronic diary by participant's LAR. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as mild (>0.0 to 2.0 cm), moderate (>2.0 to 7.0 cm) and severe (>7 cm). Pain at injection site was graded as mild (hurt if gently touched), moderate (hurt if gently touched, with crying), and severe (caused limitation of limb movement). | Within 7 Days After Supplemental Dose | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 1 | Systemic events were recorded using an e-diary by participant's LAR and included fever, decreased appetite, drowsiness/increased sleep, and irritability. Fever was defined as rectal temperature of greater than or equal to (>=) 38.0 degree Celsius and categorized as >=38.0 to 38.4 degree Celsius,>38.4 to 38.9 degree Celsius, >38.9 to 40.0 degree Celsius and >40.0 degree Celsius. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 1 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 2 | Systemic events were recorded using an e-diary by participant's LAR and included fever, decreased appetite, drowsiness/increased sleep, and irritability. Fever was defined as rectal temperature of >=38.0 degree Celsius and categorized as >=38.0 to 38.4 degree Celsius,>38.4 to 38.9 degree Celsius, >38.9 to 40.0 degree Celsius and >40.0 degree Celsius. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 2 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 3 | Systemic events were recorded using an e-diary by participant's LAR and included fever, decreased appetite, drowsiness/increased sleep, and irritability. Fever was defined as rectal temperature of >=38.0 degree Celsius and categorized as >=38.0 to 38.4 degree Celsius,>38.4 to 38.9 degree Celsius, >38.9 to 40.0 degree Celsius and >40.0 degree Celsius. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 3 | 
| Percentage of Participants With Systemic Events Within 7 Days After Dose 4 | Systemic events were recorded using an e-diary by participant's LAR and included fever, decreased appetite, drowsiness/increased sleep, and irritability. Fever was defined as rectal temperature of >=38.0 degree Celsius and categorized as >=38.0 to 38.4 degree Celsius,>38.4 to 38.9 degree Celsius, >38.9 to 40.0 degree Celsius and >40.0 degree Celsius. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Dose 4 | 
| Percentage of Participants With Systemic Events Within 7 Days After Supplemental Dose | Systemic events were recorded using an e-diary by participant's LAR and included fever, decreased appetite, drowsiness/increased sleep, and irritability. Fever was defined as rectal temperature of >=38.0 degree Celsius and categorized as >=38.0 to 38.4 degree Celsius,>38.4 to 38.9 degree Celsius, >38.9 to 40.0 degree Celsius and >40.0 degree Celsius. Decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity). Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted). | Within 7 Days After Supplemental Dose | 
| Percentage of Participants With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 3 | An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment. | From Dose 1 to 1 Month After Dose 3 (up to duration of 5 months) | 
| Percentage of Participants With Adverse Events (AEs) From Dose 4 to 1 Month After Dose 4 | An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment. | From Dose 4 to 1 Month After Dose 4 (up to duration of 1 month) | 
| Percentage of Participants With Adverse Events (AEs) From Supplemental Dose to 1 Month After Supplemental Dose | An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment. | From Supplemental Dose to 1 Month After Supplemental Dose (up to duration of 1 month) | 
| Percentage of Participants With Serious Adverse Events (SAEs) From Dose 1 to End of the Study | An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect or that was considered to be an important medical event. | From Dose 1 to End of the Study (up to duration of 17 months) | 
| Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Dose 1 to End of the Study | An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long lasting in its effects. | From Dose 1 to End of the Study (up to duration of 17 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pneumococcal Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) 1 Month After Dose 3 | IgG GMCs were determined for each of 7 pneumococcal serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) at 1 month after Dose 3. Dose 3 was third dose of c7vPnC in Group 1 and Group 2, and third dose of Prevnar 13 in Group 3. | 1 Month After Dose 3 | 
| Percentage of Participants Achieving Prespecified Level of Pneumococcal Serotype-specific Immunoglobulin G (IgG) Concentrations 1 Month After Dose 3 | Percentage of participants with pre-specified IgG concentration (>=0.35 microgram per milliliter) were determined for each of 7 pneumococcal serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) at 1 month after Dose 3. Dose 3 was third dose of c7vPnC in Group 1 and Group 2, and third dose of Prevnar 13 in Group 3. | 1 Month after Dose 3 | 
| Pneumococcal Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) 1 Month After Dose 4 | IgG GMCs were determined for each of 7 pneumococcal serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F ) at 1 month after Dose 4. Dose 4 was fourth dose of c7vPnC in Group 1 and Group 2, and fourth dose of Prevnar 13 in Group 3. | 1 Month After Dose 4 |