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

Pneumococcal Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02037984
• Other study ID #: V114-004
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 28, 2014
• Est. completion date: July 1, 2016

Study information

• Verified date: June 2019
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 341
• Est. completion date: July 1, 2016
• Est. primary completion date: July 1, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 49 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Pneumococcal Infections
• Pneumonia
• Streptococcus Pneumoniae Infection

Intervention

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.
• 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).
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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 Va — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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)
Secondary	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)
Secondary	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)