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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: Prevnar 13™; Biological: V114 Medium Dose; Biological: V114 High Dose; Biological: V114 Medium Dose with Alternative Carrier Protein; Biological: V114 High Dose with Alternative Carrier Protein

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 49 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adult: V114 Medium Dose; Adult participants will receive a single 0.5 mL intramuscular injection of medium-dose V114 on Day 1.	Biological: V114 Medium Dose; 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
Experimental: Adult: V114 High Dose; Adult participants will receive a single 0.5 mL intramuscular injection of high-dose V114 on Day 1.	Biological: V114 High Dose; 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
Experimental: Adult: V114 Medium Dose with Alternative Carrier Protein; 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; 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
Experimental: Adult: V114 High Dose with Alternative Carrier Protein; 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; 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
Experimental: Infant: V114 Medium Dose; 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; 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
Experimental: Infant: V114 High Dose; 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; 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
Experimental: Infant: V114 Medium Dose with Alternative Carrier Protein; 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; 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
Experimental: Infant: V114 High Dose with Alternative Carrier Protein; 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; 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
Active Comparator: Infant: Prevnar 13™; 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™; 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

What is the study measuring?

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)

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): September 15, 2015
• Primary Completion (Actual): April 14, 2017
• Study Completion (Actual): April 14, 2017

Study Registration Dates

• First Submitted: August 20, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (Estimate): August 24, 2015

Study Record Updates

• Last Update Posted (Actual): April 2, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-005

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