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

NCT02037984 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: V114-004
• Study Type: interventional
• Target: 341
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Streptococcus Pneumoniae Infection; Pneumococcal Infections

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (10)

• 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)

  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)

  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®

  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®

  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®

  One month following the 4th vaccination (approximately 13 to 16 months of age).

Study Arms (8)

Adult V114: 1x:1x:1x

EXPERIMENTAL

Adults receive a single vaccination on Day 1.

Biological: V114 1x:1x:1x

Adult V114: 2x:2x:2x

EXPERIMENTAL

Adults receive a single vaccination on Day 1.

Biological: V114 2x:2x:2x

Infant V114: 1x:1x:1x

EXPERIMENTAL

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: V114 1x:1x:1x

Infant V114: 2x:1x:2x

EXPERIMENTAL

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: V114 2x:1x:2x

Infant V114: 2x:2x:2x

EXPERIMENTAL

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: V114 2x:2x:2x

Infant V114: 0.5x:0.5x:2x

EXPERIMENTAL

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: V114 0.5x:0.5x:2x

Infant V114: 1x:1x:2x

EXPERIMENTAL

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: V114 1x:1x:2x

Infant Prevnar 13®

ACTIVE COMPARATOR

Infants receive 4 total vaccinations given at 2, 4, 6, and 12 to 15 months of age.

Biological: Prevnar 13®

Interventions

Prevnar 13® BIOLOGICAL

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.

Infant Prevnar 13®

V114 1x:1x:1x BIOLOGICAL

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).

Adult V114: 1x:1x:1x; Infant V114: 1x:1x:1x

V114 2x:2x:2x BIOLOGICAL

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.

Adult V114: 2x:2x:2x; Infant V114: 2x:2x:2x

V114 2x:1x:2x BIOLOGICAL

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.

Infant V114: 2x:1x:2x

V114 1x:1x:2x BIOLOGICAL

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.

Infant V114: 1x:1x:2x

V114 0.5x:0.5x:2x BIOLOGICAL

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.

Infant V114: 0.5x:0.5x:2x

Eligibility Criteria

• Age: 6 Weeks - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Infants:
• \- Healthy and able to attend all scheduled visits.
• Adults:
• \- Highly unlikely to conceive from vaccination to 6 weeks after administration of the vaccine.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 30689507 RESULT

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 16, 2014
• Study Start: January 28, 2014
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: June 24, 2019
• Results First Posted: April 30, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share