Safety and Tolerability Study for the Pneumococcal Conjugate Vaccine V114 Versus Prevnar™ (V114-001)

Study Overview
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Brief Summary
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This study is being conducted to evaluate the safety, tolerability, and immunogenicity of 15-valent pneumococcal conjugate vaccine (V114) compared to Prevnar™ in healthy adults and toddlers.

Detailed Description
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The study was extended to obtain additional sera from adult participants to support further development, validation, and performance of anti-pneumococcal antibody assays.

Official Title
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A Multicenter, Double-Blind Study of the Safety, Tolerability, and Immunogenicity of Pneumococcal Conjugate Vaccine (V114) Compared to Prevnar™ in Healthy Adults and Toddlers

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: Prevnar™
* Biological: V114, Aluminum Adjuvanted
* Biological: V114, Aluminum Nonadjuvanted


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult Stage: Adults ≥18 to 45 years of age in good health. Signed and dated informed consent prior to receipt of vaccine. Afebrile (<100.4°F [<38.0°C] oral or equivalent) on day of vaccination. Participant is able to read, understand, and complete study questionnaires (i.e., the Vaccine Report Card). Participant is able to attend all scheduled visits and to comply with the study procedures. Participant has access to a telephone. Females must have a negative urine pregnancy test. Toddler Stage: Healthy toddlers, 12-15 months of age who have previously completed a documented full 3 dose infant series of Prevnar™ at 2, 4, and 6 months of age. Participant's parent/legal guardian understands the study procedures, alternate treatments available and risks involved with the study, and voluntarily agrees to participate by giving written informed consent. Afebrile, with a rectal temperature <38.1°C (<100.5°F) or axillary temperature <37.8°C (<100.0°F) on day of vaccination. Participant's parent/legal guardian is able to read, understand, and complete study questionnaires (i.e., the Vaccination Report Card). Participant is able to attend all scheduled visits and to comply with the study procedures. Participant's parent/legal guardian has access to a telephone. Exclusion criteria: Adult Stage: Receipt of any pneumococcal polysaccharide vaccine at any time or receipt of polysaccharide conjugate vaccine after the second year of life. Known hypersensitivity to any component of the pneumococcal conjugate vaccine. Known or suspected immunocompromised persons, including persons with congenital immunodeficiency, human immunodeficiency virus (HIV) infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure (most recent serum creatinine values in medical record ≥3 mg/dL), nephritic syndrome, or other conditions associated with immunosuppression such as organ or bone marrow transplant. Functional or anatomic asplenia. History of autoimmune disease including multiple sclerosis (MS), systemic lupus, polymyositis, inclusion body myositis, dermatomyositis, Hashimoto's thyroiditis, Sjogren's syndrome, rheumatoid arthritis, other autoimmune disorders. History of chronic fatigue syndrome. Known neurologic or cognitive behavioral disorders including multiple sclerosis (MS), MS-like disease, encephalitis/myelitis, acute disseminating encephalomyelitis (ADEM), pervasive developmental disorder, and related disorders. Participant has a coagulation disorder contraindicating IM vaccination. Use of any immunosuppressive therapy (Note: topical and inhaled/nebulized steroids are permitted). Participants on corticosteroids should be excluded if they are receiving or are expected to receive, in the period from 30 days prior to Visit 1 through Visit 2, systemic doses greater than required for physiological replacement, i.e., >5 mg of prednisone (or equivalent) daily and for >2 weeks. Excluded immunosuppressive therapies also include chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation, or autoimmune disease. Any underlying illness that would complicate evaluation and completion of this study. Any licensed non-live virus vaccine administered within the 14 days prior to receipt of study vaccine or is scheduled to receive any other licensed vaccine within 30 days following receipt of study vaccine. (Exception: Inactivated influenza vaccine may be administered during the study, but must be given at least 7 days prior to receipt of the study vaccine or at least 15 days after receipt of the study vaccine.) Participant has received a licensed live virus vaccine within 30 days prior of receipt of study vaccine or is scheduled to receive vaccination with a licensed live virus vaccine within 30 days of receipt of study vaccine. Participant has received diphtheria toxoid within 6 months prior to receipt of study vaccine. Prior receipt of a blood transfusion or blood products including immune globulin administered within the 6 months before receipt of study vaccine. Investigational drugs or vaccines received within the 2 months before receipt of study vaccine. Participation in another clinical study within 42 days before the beginning or anytime during the duration of the current clinical study. Recent hospitalization for acute illness within the 3 months before receipt of study vaccine. 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. History of febrile illness (≥100.40 F [≥38.00 C] oral or equivalent) occurring within 72 hours before receipt of study vaccine. Participant is pregnant or breastfeeding or expecting to conceive within the projected duration of the study. Female participants of reproductive potential must have been using 2 acceptable methods of birth control for 2 weeks prior to enrollment, and agree to use 2 acceptable methods of birth control for 1 month after vaccination. (Acceptable methods of birth control include use of hormonal contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, tubal ligation, condoms, or abstinence). Any participant who cannot be adequately followed for safety according to the protocol plan. Participant is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study. Any other reason that in the opinion of the investigator may interfere with the evaluation required by the study. Toddler Stage: Have received less than the full 3-dose infant series of Prevnar™ or 3rd dose less than 2 months before study vaccine. Known hypersensitivity to any component of the pneumococcal conjugate vaccine. Known or suspected impairment of immunological function. Participant has a history of congenital or acquired immunodeficiency (e.g., splenomegaly). Participant or his/her mother has documented HIV infection. Functional or anatomic asplenia. History of autoimmune disease including multiple sclerosis (MS), systemic lupus, polymyositis, inclusion body myositis, dermatomyositis, Hashimoto's thyroiditis, Sjogren's syndrome, rheumatoid arthritis, other autoimmune disorders. Known neurologic or cognitive behavioral disorders including multiple sclerosis (MS), MS-like disease, encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive developmental disorder, and related disorders. Receipt of intramuscular, oral, or intravenous corticosteroid treatment within the 2 weeks prior to vaccination. (Note: Toddlers on topical and inhaled/nebulized steroids may participate in the study.) Use of systemic steroids are only permitted when the participant is receiving less than 2 mg/kg per day of prednisone (or its equivalent), or less than 20 mg/d if they weigh more than 10 kg and are not otherwise immunocompromised. Participant has received other licensed non-live vaccines administered within the 14 days before receipt of study vaccine. Participant has received a licensed live virus vaccine within 30 days prior of receipt of study vaccine (Exception: Influenza virus vaccine given according to recommended guidelines within 7 days of receiving study vaccine). Prior receipt of a blood transfusion or blood products, including immunoglobulins. Investigational drugs or vaccines received within the 2 months before receipt of study vaccine. Participation in another clinical study within 42 days before the beginning or anytime during the duration of the current clinical study. 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. A recent (<72 hours) febrile illness (rectal temperature ≥38.1°C [≥100.5°F]) occurring within 48 hours before receipt of study vaccine. History of failure to thrive. Participant has a coagulation disorder contraindicating IM vaccination. Participant and his/her mother is documented hepatitis B surface antigen-positive. Any toddler who cannot be adequately followed for safety according to the protocol plan. Participant's parent/legal guardian is unlikely to adhere to study procedures, keep appointments, or is planning to relocate during the study. Any other reason that in the opinion of the investigator may interfere with the evaluation required by the study.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 45 Years

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 |
| --- | --- |
| Active Comparator: Prevnar™ - Adult Cohort<br>Healthy adult participants received a single 0.5 mL intramuscular injection of Prevnar™ on Day 1. | Biological: Prevnar™<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), serotype 6B (4.4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>|
| Experimental: V114 Adjuvanted -Toddler Cohort<br>Healthy toddler (12-15 months of age) participants who had completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of aluminum adjuvanted V114 on Day 1. | Biological: V114, Aluminum Adjuvanted<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.0 mcg each), serotype 6B (4.0 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>|
| Experimental: V114 Nonadjuvanted-Toddler Cohort<br>Healthy toddlers (12-15 months of age) participants who completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of non-adjuvanted V114 on Day 1. | Biological: V114, Aluminum Nonadjuvanted<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.0 mcg each), serotype 6B (4.0 mcg) in each 0.5 mL dose.<br>|
| Active Comparator: Prevnar™- Toddler Cohort<br>Healthy toddlers (12-15 months of age) participants who had previously completed a documented full 3-dose infant series of Prevnar™ received a single 0.5 mL intramuscular injection of Prevnar™ on Day 1. | Biological: Prevnar™<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), serotype 6B (4.4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>|
| Experimental: V114 Adjuvanted -Adult Cohort<br>Healthy adult participants received a single 0.5 mL intramuscular injection of aluminum adjuvanted V114 on Day 1. | Biological: V114, Aluminum Adjuvanted<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2.0 mcg each), serotype 6B (4.0 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult: Percentage of Participants With Any Adverse Event | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to Day 14 after vaccination | 
| Toddler: Percentage of Participants With Any Adverse Event | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. | Up to Day 14 after vaccination | 
| Adult: Percentage of Participants With Any Serious Adverse Event | A serious adverse event (SAE) is an AE that results in death, 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. | Up to Day 14 after vaccination | 
| Toddler: Percentage of Participants With Any Serious Adverse Event | A serious adverse event (SAE) is an AE that results in death, 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. | Up to Day 14 after vaccination | 
| Adult: Percentage of Participants With Any Vaccine-related Adverse Event | An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Relatedness of the AE to study vaccine was determined by the investigator. | Up to Day 14 after vaccination | 
| Toddler: Percentage of Participants With Any Vaccine-related Adverse Event | An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Relatedness of the AE to study vaccine was determined by the investigator. | Up to Day 14 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult: Percentage of Participants Achieving the Immunoglobulin G (IgG) Serotype-specific Threshold Value of ≥ 0.35μg/mL | Immunoglobulin G (IgG) for the serotypes contained in V114 was determined using an electrochemiluminescence assay. | Day 30 after vaccination | 
| Toddler: Percentage of Participants Achieving the Immunoglobulin G (IgG) Serotype-specific Threshold Value of ≥ 0.35μg/mL | Immunoglobulin G (IgG) for the serotypes contained in V114 was determined using an electrochemiluminescence assay. | Day 30 after vaccination | 
| Adult: Geometric Mean Concentration (GMC) of Pneumococcal Serotype Immunoglobulin G (IgG) Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | Day 30 after vaccination | 
| Toddler: Geometric Mean Concentration (GMC) of Pneumococcal Serotype Immunoglobulin G (IgG) Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | Day 30 after vaccination | 
| Adult: Percentage of Participants Achieving Opsonophagocytic Activity (OPA) ≥1:8 | OPA for the serotypes contained in V114 was determined using a Multiplex Opsonophagocytic Assay. | Day 30 after vaccination | 
| Toddler: Percentage of Participants Achieving Opsonophagocytic Activity (OPA) ≥1:8 | OPA for the serotypes contained in V114 was determined using a Multiplex Opsonophagocytic Assay. | Day 30 after vaccination | 
| Adult: Geometric Mean Titer (GMT) of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) | OPA for the serotypes contained in V114 was determined using a Multiplex Opsonophagocytic Assay | Day 30 after vaccination | 
| Toddler: Geometric Mean Titer (GMT) of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) | OPA for the serotypes contained in V114 was determined using a Multiplex Opsonophagocytic Assay | Day 30 after vaccination | 

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