Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-028)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of V114 administered subcutaneously or intramuscularly in healthy Japanese infants (3 months of age).

Official Title
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A Phase I, Double-Blind, Randomized, Multicenter Trial of the Safety,Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: Pneumococcal 13-valent Conjugate Vaccine (PCV13)
* Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy (based on a review of medical history and physical examination) based on the clinical judgment of the investigator. Male or female 3 months of age inclusive (3 months of age to1 day prior to 4 months of age), at the time of obtaining the informed consent. Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent. Exclusion Criteria: Has a history of invasive pneumococcal disease (positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture positive pneumococcal disease. Has a known hypersensitivity to vaccines, any component of the pneumococcal conjugate vaccine or any diphtheria toxoid-containing vaccine Has any contraindication to the PCV13 and/or diphtheria, tetanus, acellular pertussis, inactivated polio vaccine (DTaP-IPV) being administered in the study (Refer to approved labeling for contraindication details on PCV13 and DTaPIPV vaccine). Has a recent febrile illness (axillary temperature ≥37.5°C) occurring within 72 hours prior to receipt of study vaccine. Has a known or suspected impairment of immunological function. Has a history of congenital or acquired immunodeficiency. Has or his/her mother has a documented hepatitis B surface antigen - positive test. Has a known functional or anatomic asplenia. Has failure to thrive based on the clinical judgement of the investigator. Has thrombocytopenia or a known coagulation disorder contraindicating intramuscular vaccination. Has a history of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Bechet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, type 1 diabetes mellitus, or other autoimmune disorders). Has a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders. Has received a dose of any pneumococcal and/or DTaP-IPV vaccine (or vaccine containing any DTaP-IPV component) prior to study entry. Meets one or more of the following systemic corticosteroid exclusion criteria: has received systemic corticosteroids (equivalent of ≥ 2 mg/kg total daily dose of prednisone or ≥ 20 mg/d for persons weighing > 10 kg) for ≥ 14 consecutive days and has not completed this course of treatment at least 30 days prior to trial randomization, has received systemic corticosteroids within 14 days prior to the first dose of study vaccine at randomization, and is expected to require systemic corticosteroids (equivalent of ≥ 2 mg/kg total daily dose of prednisone or ≥ 20 mg/d for persons weighing > 10 kg) for ≥ 14 consecutive days within 14 days prior to or 30 days after each vaccination during conduct of the study.(Topical, ophthalmic and inhaled steroids are permitted.) Has received other licensed non-live vaccines within the 14 days before receipt of first dose of study vaccine. Has received a licensed live virus vaccine within the 28 days before receipt of first dose of study vaccine. Has received a blood transfusion or blood products, including immunoglobulins before receipt of first dose of study vaccine. Has participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included; these will be reviewed on a case by case basis for approval by the Sponsor. Has any other reason that, in the opinion of the investigator, may interfere with the evaluation required by the study. (Refer to the Vaccination Guideline in Japan). Reasons may include, but are not limited to, being unable to keep appointments or planning to relocate during the study. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 3 Months

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V114-SC<br>Infant participants will receive a single 0.5 mL subcutaneous (SC) injection of V114 on Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine [Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV) at the same time as V114-SC. | Biological: V114<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)<br>* Single SC dose of 0.5 mL at Visits 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).<br>|
| Experimental: V114-IM<br>Infant participants will receive a single 0.5 mL intramuscular (IM) injection of V114 at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine (DTaP-IPV) at the same time as V114-IM. | Biological: V114<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)<br>* Single SC dose of 0.5 mL at Visits 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).<br>|
| Active Comparator: PCV13-SC<br>Infant participants will receive a single 0.5 mL subcutaneous (SC) injection of pneumococcal 13-valent conjugate vaccine (PCV13) at Visit 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age). Infant participants will receive a single 0.5 mL SC injection of concomitant study vaccine (DTaP-IPV) at the same time as PCV13-SC. | Biological: Pneumococcal 13-valent Conjugate Vaccine (PCV13)<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F, serotype 6B in each 0.5. mL dose.<br>* Other names: PREVNAR 13®;Biological: Adsorbed Diphtheria-purified Pertussis-tetanus-inactivated polio (Sabin strain) Combined Vaccine (DTaP-IPV)<br>* Single SC dose of 0.5 mL at Visits 1, 2, 3 and 5 (approximately 3, 4, 5, and 12 to 15 months of age).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Solicited Injection-site Adverse Event (AE) | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited injection-site AEs were injection site erythema (redness), injection site induration (hard lump), injection site pain and injection site swelling. | Day 1 to Day 14 post each vaccination | 
| Percentage of Participants With a Solicited Systemic Adverse Event | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Solicited systemic AEs were decreased appetite (appetite loss), somnolence (drowsiness), irritability and urticaria (hives/welts). | Day 1 to Day 14 post each vaccination | 
| Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) | An SAE is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator. | Up to 4 weeks post vaccination 4 ( 14.5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Meeting the Serotype-specific Immunoglobulin G (IgG) Threshold of ≥0.35 µg/mL | Serotype-specific pneumococcal IgG antibody was measured using pneumococcal electrochemiluminescence (PnECL). The percentage of participants with serotype-specific IgG ≥0.35 µg/mL was summarized for each serotype. | One month post vaccination 3 ( 3 months after Vaccination 1) | 
| Serotype-specific IgG Geometric Mean Concentrations (GMCs) | The anti-pneumococcal polysaccharide (PnPs) serotype-specific IgG Geometric Mean Concentrations (GMCs) were determined using an electrochemiluminescence assay. | 1 month post vaccination 3 ( 3 months after Vaccination 1) | 
| Percentage of Participants Meeting Threshold Values for Protective Responses to DTaP-IPV (Diphtheria Toxin, Tetanus Toxin, Pertussis Toxin, Pertussis Filamentous Hemagglutinin (FHA) and Polio Virus Type 1/2/3) | DTaP-IPV antibody titers were measured by neutralization assay (diphtheria toxin and poliovirus 1/2/3), particle agglutination assay (tetanus toxin) and enzyme-linked immunosorbent assay (ELISA) methodology (pertussis PT and pertussis FHA) 1 month post vaccination 3. Threshold values were: Diphtheria toxin level ≥0.1 IU/mL, Pertussis PT level ≥10 EU/mL, Pertussis FHA level ≥10 EU/mL, Tetanus toxin level ≥0.01 IU/mL, Neutralizing antibody (NA) titers of Polio virus types 1/2/3 ≥1:8. | 1 month post vaccination 3 ( 3 months after Vaccination 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumococcal Vaccines