A Study to Evaluate the Safety, Tolerability and Immunogenicity of V114 in Healthy Adults and Infants (V114-005)

Study Overview
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Brief Summary
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This study is designed to assess the effect of different dose levels of pneumococcal polysaccharide and adjuvant on the safety and immunogenicity of V114 in healthy adults and infants.

Official Title
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A Phase I-II, Randomized, Double-Blind, Study to Evaluate the Safety, Tolerability, and Immunogenicity of Different Formulations of V114 in Healthy Adults and Infants

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114 Medium Dose
* Biological: V114 High Dose
* Biological: V114 Medium Dose with Alternative Carrier Protein
* Biological: V114 High Dose with Alternative Carrier Protein
* Biological: Prevnar 13™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult Cohort: 18 to 49 years and in good health Highly unlikely to conceive from vaccination through 6 weeks after administration of the study vaccine. Infant Cohort: approximately 2 months (42 to 90 days) and in good health. Exclusion Criteria: Adult cohort: Prior administration of any pneumococcal vaccine History of invasive pneumococcal disease Known hypersensitivity to any vaccine component Known or suspected impairment of immune function Coagulation disorder contraindicating intramuscular vaccination Received a blood transfusion or blood products within 6 months Participated in another clinical study of an investigational product within 2 months Breast feeding. Infant cohort: Prior administration of any pneumococcal vaccine Known hypersensitivity to any vaccine component Known or suspected impairment of immune function History of congenital or acquired immunodeficiency Has or mother has documented Human Immunodeficiency virus (HIV) infection Has or mother has documented hepatitis B surface antigen positive result Functional or anatomic asplenia History of failure to thrive Coagulation disorder contraindicating intramuscular vaccination History of autoimmune disease or autoimmune disorder Known neurologic or cognitive behavioral disorder Received systemic corticosteroids within 14 days Received other licensed non-live vaccine within 14 days Received other licensed live virus vaccine within 30 days Received a blood transfusion or blood products Participated in another clinical study of an investigational product History of invasive pneumococcal disease

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 49 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 |
| --- | --- |
| Experimental: Adult: V114 Medium Dose<br>Adult participants will receive a single 0.5 mL intramuscular injection of medium-dose V114 on Day 1. | Biological: V114 Medium Dose<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose<br>|
| Experimental: Adult: V114 High Dose<br>Adult participants will receive a single 0.5 mL intramuscular injection of high-dose V114 on Day 1. | Biological: V114 High Dose<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (4 mcg each), serotype 6B (8 mcg), and Merck Aluminum Phosphate Adjuvant (250 mcg) in each 0.5 mL dose<br>|
| Experimental: Adult: V114 Medium Dose with Alternative Carrier Protein<br>Adult participants will receive a single 0.5 mL intramuscular injection of medium-dose V114 with alternative carrier protein on Day 1. | Biological: V114 Medium Dose with Alternative Carrier Protein<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg), and Merck Aluminum Phosphate Adjuvant (125 mcg) with alternative carrier protein in each 0.5 mL dose<br>|
| Experimental: Adult: V114 High Dose with Alternative Carrier Protein<br>Adult participants will receive a single 0.5 mL intramuscular injection of high-dose V114 with alternative carrier protein on Day 1. | Biological: V114 High Dose with Alternative Carrier Protein<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (4 mcg each), serotype 6B (8 mcg), and Merck Aluminum Phosphate Adjuvant (250 mcg) with alternative carrier protein in each 0.5 mL dose<br>|
| Experimental: Infant: V114 Medium Dose<br>Infant participants will receive a 0.5 mL intramuscular injection of medium-dose V114 at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 Medium Dose<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose<br>|
| Experimental: Infant: V114 High Dose<br>Infant participants will receive a 0.5 mL intramuscular injection of high-dose V114 at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 High Dose<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (4 mcg each), serotype 6B (8 mcg), and Merck Aluminum Phosphate Adjuvant (250 mcg) in each 0.5 mL dose<br>|
| Experimental: Infant: V114 Medium Dose with Alternative Carrier Protein<br>Infant participants will receive a 0.5 mL intramuscular injection of medium-dose V114 with alternative carrier protein at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 Medium Dose with Alternative Carrier Protein<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg), and Merck Aluminum Phosphate Adjuvant (125 mcg) with alternative carrier protein in each 0.5 mL dose<br>|
| Experimental: Infant: V114 High Dose with Alternative Carrier Protein<br>Infant participants will receive a 0.5 mL intramuscular injection of high-dose V114 with alternative carrier protein at 2, 4, 6, and 12 to 15 months of age. | Biological: V114 High Dose with Alternative Carrier Protein<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F (4 mcg each), serotype 6B (8 mcg), and Merck Aluminum Phosphate Adjuvant (250 mcg) with alternative carrier protein in each 0.5 mL dose<br>|
| Active Comparator: Infant: Prevnar 13™<br>Infant participants will receive a 0.5 mL intramuscular injection of Prevnar 13™ at 2, 4, 6, and 12 to 15 months of age. | Biological: Prevnar 13™<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 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 |
| --- | --- | --- |
| Adults: Percentage of Participants With an 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 6 weeks after vaccination | 
| Infants: Percentage of Participants With an 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. | Up to 1 month after Vaccination 4 (Month 11-15) | 
| Infants: Percentage of Participants With Study Vaccination Withdrawn Due to an 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. | Up to time of Vaccination 4 (Month 10-13) | 
| Infants: Percentage of Participants With a Solicited Injection-site Adverse Event | Solicited injection-site AEs were injection-site erythema, injection-site induration, injection-site pain, and injection-site swelling. | Up to 14 days after any vaccination | 
| Infants: Percentage of Participants With a Solicited Systemic Adverse Event | Solicited systemic AEs were irritability, decreased appetite, somnolence, and urticaria. | Up to 14 days after any vaccination | 
| Infants: Geometric Mean Concentration (GMC) of Pneumococcal Serotype IgG Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | 1 month after Vaccination 3 (Month 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adults: Geometric Mean Concentration (GMC) of Pneumococcal Serotype IgG Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | 1 month after vaccination | 
| Adults: Geometric Mean Fold Rise (GMFR) From Baseline in GMC of Pneumococcal Serotype IgG Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. GMFR is defined as the geometric mean of the ratio of concentration at 1 month after vaccination divided by concentration at baseline. | Baseline and 1 month after vaccination | 
| Infants: Percentage of Participants With GMC ≥0.35 µg/mL at 1 Month After Vaccination 3 | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | 1 month after Vaccination 3 (Month 5) | 
| Infants: Percentage of Participants With GMC ≥0.35 µg/mL Before Vaccination 4 | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | Before Vaccination 4 (Month 10-13) | 
| Infants: Percentage of Participants With GMC ≥0.35 µg/mL at 1 Month After Vaccination 4 | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | 1 month after Vaccination 4 (Month 11-15) | 
| Infants: Geometric Mean Concentration of Pneumococcal Serotype IgG Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | Before Vaccination 4 (Month 10-13) | 
| Infants: Geometric Mean Concentration of Pneumococcal Serotype IgG Antibodies | Pneumococcal serotype-specific IgG was measured in serum using an electrochemiluminescence assay. | 1 month after Vaccination 4 (Month 11-15) |