Study Evaluating Pneumococcal Vaccine in Healthy Infants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine (13vPnC) in healthy infants. This is the first study with this vaccine in infants.

Official Title
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A Phase I/II, 2-stage, Randomized, Double-Blind Trial of the Safety, Tolerability and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine (Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) in Healthy Infants

Conditions
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Healthy Subjects, Pneumococcal Infections

Intervention / Treatment
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* Biological: 13-Valent Pneumococcal Conjugate Vaccine (13vPnC)
* Biological: 7-Valent Pneumococcal Conjugate Vaccine (7vPnC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 weeks to 14 weeks (42-98 days of age) at time of enrollment, In good health as determined by medical history, physical examination and judgment of the investigator, Subject must have been born ≥36 weeks of gestational age, Subject must be available for entire study period and whose parent/legal guardian can be reached by telephone, Parent/legal guardian must be able to understand and sign an informed consent form prior to participation and complete a parent worksheet during study participation. Exclusion Criteria: Previous vaccination with licensed or investigational pneumococcal vaccine, Previous vaccination with Hib conjugate, DTaP or IPV vaccines, Contraindication to immunization with HepB, Hib conjugate, DTaP or IPV vaccines, Significant neurological disorder or history of seizure including febrile seizure, or significant stable or evolving disorders such as cerebral palsy, encephalopathy, hydrocephalus or other significant disorders. Does not include resolving syndromes due to birth trauma such as Erb palsy, Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection, History of culture-proven invasive disease caused by S. pneumoniae, Previous anaphylactic reaction to any vaccine or vaccine components, Major known congenital malformation or serious chronic disorders, Participation in another investigational study (however, observation-only trials are permitted), Known or suspected immune deficiency/suppression, Receipt of blood products or gamma globulin (including Hepatitis B immunoglobulin and monoclonal antibody; eg, Synagis®).

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 13vPnC<br> | Biological: 13-Valent Pneumococcal Conjugate Vaccine (13vPnC)<br> <br> |
| Active Comparator: 7vPnC<br> | Biological: 7-Valent Pneumococcal Conjugate Vaccine (7vPnC)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Pre-Specified Local Reactions | Local reaction events were collected using a paper worksheet. Tenderness was scaled as Any (tenderness present); Significant (Sig.) (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (Mod.)(2.5 to 7.0 cm); Severe (Sev.)(> 7.0 cm). Participants may be represented in more than 1 category. | Within 15 days after each dose | 
| Percentage of Participants Reporting Pre-Specified Systemic Events | Systemic events (fever [Fv] ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C, decreased (decr.) appetite, irritability, increased sleep, decreased sleep, use of medication (Med.)to prevent symptoms (sx), and use of medication to treat symptoms) were reported using a paper worksheet. Participants may be represented in more than 1 category. | Within 15 days after each dose | 
| Percentage of Participants Achieving Antibody Level ≥0.35μg/mL in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Percentage of participants achieving World Health Organization (WHO) predefined antibody threshold ≥0.35μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants. | one month after 3-dose infant series (at 7 months of age) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Antibody Level ≥0.35μg/mL in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose | Percentages of participants achieving WHO predefined antibody threshold ≥0.35μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based on the observed proportion of participants. | One month after the toddler dose (at 13 to 16 months of age) | 
| Geometric Mean Antibody Concentration in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Antibody geometric mean concentration (GMC) as measured by enzyme-linked immunosorbent assay (ELISA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC ratios (13vPnC/7vPnC) and corresponding 2-sided 95% CI were evaluated. | One month after 3-dose infant series (at 7 months of age) | 
| Geometric Mean Concentration in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose | Antibody geometric mean concentration (GMC) as measured by ELISA with their corresponding 95% CI immediately before and after the toddler dose for 7 common pneumococcal serotypes (Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | Immediately before (12 to 15 months of age) and one month after the toddler dose (13 to 16 months of age) | 
| Percentage of Participants Achieving Predefined Antibody Levels for Haemophilus Influenzae Type b, Diphtheria Toxoid, Polio, Pertussis, Tetanus, and Hepatitis B in 13vPnC Group Relative to 7vPnC Group After the Infant Series | Percentage of participants achieving predefined antibody threshold levels for Haemophilus Influenzae Type b (Hib) polyribosylribitol phosphate (PRP), Diphtheria Toxoid, Polio (Types 1, 2, and 3), Pertussis (filamentous hemagglutinin [FHA], Pertussis Toxoid, and Pertactin), Tetanus, and Hepatitis B with the corresponding 95% CI for each concomitant antigen are presented. | One month after the infant series (7 months of age) | 
| Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the Infant Series |  | one month after the infant series (7 months of age) | 
| Geometric Mean Antibody Concentration of Hepatitis B in 13vPnC Group Relative to 7vPnC Group After the Infant Series | GMCs of anti-hepatitis B surface antigen (HBsAg) using a Food and Drug Administration (FDA) approved in vitro diagnostic kit are presented. | one month after the infant series (7 months of age) | 
| Geometric Mean Antibody Concentration Diphtheria Toxoid and Anti-Tetanus Toxoid in 13vPnC Group Relative to 7vPnC Group After the Infant Series |  | one month after the infant series (7 months of age) | 
| Geometric Mean Antibody Concentration of Polio in 13vPnC Group Relative to 7vPnC Group After the Infant Series |  | one month after the infant series (7 months of age) | 
| Geometric Mean Antibody Concentration of Pertussis Antigens in 13vPnC Group Relative to 7vPnC Group After the Infant Series |  | one month after the infant series (7 months of age) | 
| Percentage of Participants Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group Relative to 7vPnC Group After the 3-Dose Infant Series | Percentage of participants achieving functional antibody titer ≥1:8 as measured by opsonophagocytic activity assay (OPA) along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. | one month after the infant series (7 months of age) | 
| Percentage of Participants Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose | Percentage of participants achieving functional antibody titer ≥1:8 as measured by opsonophagocytic activity assay (OPA) along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) were assessed. Results are reported for the serotypes with a determinate antibody titer. | One month after the toddler dose (13 to 16 months of age) | 
| Geometric Mean Antibody Titer (OPA) in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose | Antibody functionality/geometric mean titer (GMT) as measured by opsonophagocytic activity assay (OPA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) were assessed. Results are reported for the serotypes with a determinate antibody titer. | One month after the Toddler Dose (13 to 16 months of age) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infant Vaccine