Safety, Tolerability and Immunogenicity of V114 in Healthy Adults and Infants (V114-004)

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

This study is designed to assess the safety, tolerability, and immunogenicity of 5 different formulations of V114 in healthy adults and infants. Adults only will be enrolled in Period 1 and infants only will be enrolled in Period 2; Period 1 will complete prior to the start of Period 2.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections; Streptococcus Pneumoniae Infection
• Intervention / Treatment: Biological: V114 1x:1x:1x; Biological: V114 2x:2x:2x; Biological: V114 2x:1x:2x; Biological: V114 0.5x:0.5x:2x; Biological: V114 1x:1x:2x; Biological: Prevnar 13®

• Study Type: Interventional
• Enrollment (Actual): 341
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 49 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria

Infants:

- Healthy and able to attend all scheduled visits.

Adults:

- Highly unlikely to conceive from vaccination to 6 weeks after administration of the vaccine.

Exclusion Criteria

Infants and Adults:

• Prior administration of any pneumococcal vaccine, any non-live vaccine within 14 days, or any live vaccine within 30 days.
• History of invasive pneumococcal disease.
• Known hypersensitivity to any vaccine component.
• Received systemic corticosteroids within 14 days of first vaccination.
• Known or suspected impairment of immune function.
• Febrile illness within 72 hours before vaccination.
• Received blood transfusion or blood products within 30 days. Infants
• Mother has documented human immunodeficiency virus or is hepatitis B surface antigen positive.
• Has asplenia or failure to thrive.

Adults:

- Is breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Adult V114: 1x:1x:1x; Adults receive a single vaccination on Day 1.	Biological: V114 1x:1x:1x; V114 1x:1x:1x contains 2.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 4.0 μg of polysaccharide serotype 6B; and 125 µg of Aluminum Phosphate Adjuvant (APA).
EXPERIMENTAL: Adult V114: 2x:2x:2x; Adults receive a single vaccination on Day 1.	Biological: V114 2x:2x:2x; V114 2x:2x:2x contains 4.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 8.0 μg of polysaccharide serotype 6B; and 250 µg of APA.
EXPERIMENTAL: Infant V114: 1x:1x:1x; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: V114 1x:1x:1x; V114 1x:1x:1x contains 2.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 4.0 μg of polysaccharide serotype 6B; and 125 µg of Aluminum Phosphate Adjuvant (APA).
EXPERIMENTAL: Infant V114: 2x:1x:2x; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: V114 2x:1x:2x; V114 2x:1x:2x contains 4.0 μg of polysaccharide serotypes 6A, 18C, 19A, 19F, and 23F; 2.0 μg of polysaccharide serotypes 1, 3, 4, 5, 7F, 9V, 14, 22F, and 33F; 8.0 μg of polysaccharide serotype 6B; and 250 µg of APA.
EXPERIMENTAL: Infant V114: 2x:2x:2x; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: V114 2x:2x:2x; V114 2x:2x:2x contains 4.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 8.0 μg of polysaccharide serotype 6B; and 250 µg of APA.
EXPERIMENTAL: Infant V114: 0.5x:0.5x:2x; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: V114 0.5x:0.5x:2x; V114 0.5x:0.5x:2x contains 1.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 2.0 μg of polysaccharide serotype 6B; and 250 µg of APA.
EXPERIMENTAL: Infant V114: 1x:1x:2x; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: V114 1x:1x:2x; V114 1x:1x:2x contains 2.0 μg of polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F; 4.0 μg of polysaccharide serotype 6B; and 250 µg of APA.
ACTIVE_COMPARATOR: Infant Prevnar 13®; Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.	Biological: Prevnar 13®; Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 µg each), and 6B (4.4 µg) in each 0.5 mL dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Adult Participants Experiencing ≥1 Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 14 days
Percentage of Adult Participants Discontinuing From Study Treatment Due to an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to 14 days
Percentage of Infant Participants Experiencing ≥1 Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. For infants, AEs were monitored for up to 14 days following each vaccination.	Up to 14 days after the 4th vaccination (approximately 12.5 to 15.5 months of age)
Percentage of Infant Participants Discontinuing From Study Treatment Due to an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. For infants, AEs were monitored for up to 14 days following each vaccination.	Up to 14 days after the 4th vaccination (approximately 12.5 to 15.5 months of age)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 3 (PD3) in Infants: V114 1x:1x:1x vs. Prevnar 13®	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD3 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 7 (1 month PD3)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 3 (PD3) in Infants: V114 2x:1x:2x vs. Prevnar 13®	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD3 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 7 (1 month PD3)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 3 (PD3) in Infants: V114 2x:2x:2x vs. Prevnar 13®	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD3 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 7 (1 month PD3)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 3 (PD3) in Infants: V114 0.5x:0.5x:2x vs. Prevnar 13®	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD3 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 7 (1 month PD3)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 3 (PD3) in Infants: V114 1x:1x:2x vs. Prevnar 13®	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD3 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 7 (1 month PD3)
Estimated Fold-Rise Per-Unit Change in Serotype-specific Antibody Concentrations Following an Increase in Polysaccharide Concentrations in Infants at 1 Month Postdose 3 (PD3)	A mulitvariate regression model was used to evaluate the impact of increasing polysaccharide concentration from 1x to 2x on the natural logarithm of serotype-specific antibody concentrations 1 month PD3. Data points show the mean estimated fold-rise-per-unit change in antibody concentration following an increase from 1x to 2x in polysaccharide concentration. For each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) serotypes, values >1.0 show an increase in antibody concentration whereas values <1.0 show a decrease in antibody concentration.	Month 7 (1 month PD3)
Estimated Fold-Rise Per-Unit Change on Serotype-specific Antibody Concentrations Following an Increase in Aluminum Phosphate Adjuvant (APA) Concentration 1 Month Postdose 3 (PD3) in Infants	A mulitvariate regression model was used to evaluate the impact of increasing APA concentration on the natural logarithm of serotype-specific antibody concentrations 1 month PD3. Data points show the mean estimated fold-rise-per-unit change in antibody concentration following an increase in APA. For each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) serotypes, values >1.0 show an increase in antibody concentration whereas values <1.0 show a decrease in antibody concentration.	Month 7 (1 month PD3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Infant Participants Achieving the Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 3 (PD3): V114 Formulations With 2x Aluminum Phosphate Adjuvant (APA)	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation with 2x APA and varying pneumococcal polysaccharide.	Month 7 (1 month PD3)
Percentage of Infant Participants Achieving the Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 3 (PD3): V114 Formulations With 1x Aluminum Phosphate Adjuvant (APA)	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation with 1x APA and varying pneumococcal polysaccharide.	Month 7 (1 month PD3)
Percentage of Infant Participants Achieving the Pneumococcal Immunoglobulin G (IgG) Serotype-specific Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 4 (PD4): V114 1x:1x:1x vs Prenar 13®	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation.	One month following the 4th vaccination (approximately 13 to 16 months of age).
Percentage of Infant Participants Achieving the Pneumococcal Immunoglobulin G (IgG) Serotype-specific Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 4 (PD4): V114 2x:1x:2x vs Prenar 13®	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation.	One month following the 4th vaccination (approximately 13 to 16 months of age).
Percentage of Infant Participants Achieving the Pneumococcal Immunoglobulin G (IgG) Serotype-specific Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 4 (PD4): V114 2x:2x:2x vs Prenar 13®	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation.	One month following the 4th vaccination (approximately 13 to 16 months of age).
Percentage of Infant Participants Achieving the Pneumococcal Immunoglobulin G (IgG) Serotype-specific Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 4 (PD4): V114 0.5x:0.5x:2x vs Prenar 13®	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation.	One month following the 4th vaccination (approximately 13 to 16 months of age).
Percentage of Infant Participants Achieving the Pneumococcal Immunoglobulin G (IgG) Serotype-specific Antibody Threshold Value of ≥0.35 μg/mL at 1 Month Postdose 4 (PD4): V114 1x:1x:2x vs Prenar 13®	The percentage of infant participants with antibody responses meeting the World Health Organization (WHO)-accepted threshold value of ≥0.35 μg/mL was determined for each Prevnar 13®-type (PT) or non-Prevnar 13®-type (non-PT) pneumococcal serotype. Antibody levels were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay for each V114 formulation.	One month following the 4th vaccination (approximately 13 to 16 months of age).
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month Postdose 4 (PD4) in Infants	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month PD4 following V114 or Prevnar 13® treatment were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay.	One month following the 4th vaccination (approximately 13 to 16 months of age)
Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month After Vaccination in Adults	The IgG antibody GMCs of each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month after a single vaccination with V114 were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay. Data reflect the GMC of each serotype.	Month 2 (1 month after a single vaccination)
Percentage of Participants With ≥4-fold-rise From Baseline in Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibodies at 1 Month After Vaccination in Adults	The percentage of participants with ≥4-fold-rise from baseline in each Prevnar 13®-type (PT) or non-Prevnar 13® type (non-PT) serotype at 1 month after a single vaccination with V114 were determined with the pneumococcal electrochemiluminescence (Pn ECL) assay.	Month 2 (1 month after a single vaccination)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Rupp R, Hurley D, Grayson S, Li J, Nolan K, McFetridge RD, Hartzel J, Abeygunawardana C, Winters M, Pujar H, Benner P, Musey L. A dose ranging study of 2 different formulations of 15-valent pneumococcal conjugate vaccine (PCV15) in healthy infants. Hum Vaccin Immunother. 2019;15(3):549-559. doi: 10.1080/21645515.2019.1568159. Epub 2019 Feb 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 28, 2014
• Primary Completion (ACTUAL): July 1, 2016
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: January 14, 2014
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (ESTIMATE): January 16, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Infections; Communicable Diseases; Pneumococcal Infections; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No