Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025) (PNEU-PED-EU-1)

• ClinicalTrials.gov Identifier: NCT04031846
• Recruitment Status: Completed
• First Posted: July 24, 2019
• Last Update Posted: December 16, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: July 22, 2019
• First Posted Date: July 24, 2019
• Last Update Posted Date: December 16, 2021
• Actual Study Start Date: September 4, 2019
• Actual Primary Completion Date: August 5, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2021)

• Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE)s [ Time Frame: Up to 14 days post any vaccination ]
  Injection-site AEs solicited on the Vaccine Report Card were redness, swelling, hard lump, and pain/tenderness. The percentage of participants with 1 or more solicited injection-site AEs will be assessed.
• Percentage of Participants that Report at Least 1 Solicited Systemic AE [ Time Frame: Up to 14 days post any vaccination ]
  Systemic AEs solicited on the Vaccine Report Card were irritability, drowsiness, hive/welts, and appetite loss. The percentage of participants with 1 or more solicited systemic AEs will be assessed
• Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE) [ Time Frame: Up to 6 months post last vaccination ]
  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs that was reported as at least possibly related to the study drug will be assessed.
• Anti-pneumococcal Polysaccharide (PnPs) Serotype-specific IgG Geometric Mean Concentrations (GMC) for Each Serotype at 30 Days Post Toddler Dose (PTD) [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL). The GMC for each serotype contained in V114 will be assessed.
• Percentage of Participants Who Meet Serotype-specific Immunoglobin G (IgG) Threshold Value of ≥0.35 μg/mL) for Each Serotype Contained in V114: 30 Days Post Toddler Dose (PTD) [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL). The percentage of participants that achieve the threshold value of ≥0.35 μg/mL will be assessed.

Original Primary Outcome Measures (submitted: July 22, 2019)

• Percentage of Participants That Report at Least 1 Solicited Injection-site Adverse Event (AE)s [ Time Frame: Up to 14 days post any V114 vaccination ]
  Injection-site AEs solicited on the Vaccine Report Card were redness, swelling, hard lump, and pain/tenderness. The percentage of participants with 1 or more solicited injection-site AEs will be assessed.
• Percentage of Participants that Report at Least 1 Solicited Systemic AE [ Time Frame: Up to 14 days post any V114 vaccination ]
  Systemic AEs solicited on the Vaccine Report Card were fever, irritability, drowsiness, hive/welts, and appetite loss. The percentage of participants with 1 or more solicited systemic AEs will be assessed
• Percentage of Participants That Report at Least 1 Vaccine-related Serious Adverse Event (SAE) [ Time Frame: Day 1 up to 6 months post last V114 vaccination ]
  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs that was reported as at least possibly related to the study drug will be assessed.
• Percentage of Participants Who Meet Serotype-specific Immunoglobin G (IgG) Threshold Value of ≥0.35 μg/mL) for Each Serotype Contained in V114: 30 days Post Toddler Dose (PTD) [ Time Frame: 30 days PTD ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal electrochemiluminescence (PnECL). The percentage that achieve the GMC threshold value of ≥0.35 μg/mL will be assessed.

Current Secondary Outcome Measures (submitted: March 24, 2021)

• Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa: 30 Days PTD [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced antibodies for the antigens contained in Infanrix. The percentage of participants that achieve the antigen-specific threshold value will be assessed.
• Anti-rotavirus Immunoglobulin A (IgA) Geometric Mean Titers (GMTs) of Rotarix™: 30 Days Post Primary Series (PPS) [ Time Frame: 30 days PPS (Postdose 2 for fullterm infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced antibodies (Immunoglobin A; [IgA]) for the antigens contained in Rotarix™. The GMT for each antigen contained in Rotarix™ will be assessed.
• Anti-PnPs Serotype-specific IgG Geometric Mean Concentrations (GMCs) for Each Serotype Contained in V114: 30 Days Post Primary Series (PPS) [ Time Frame: 30 days PPS; (Postdose 2 for full-term infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL. The GMC for each serotype contained in V114 will be assessed.
• Percentage of Participants Who Meet Serotype-specific Immunoglobin G (IgG) Threshold Value of ≥0.35 μg/mL for Each Serotype Contained in V114; 30 Days PPS [ Time Frame: 30 days PPS (Postdose 2 for full-term infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL. The percentage of participants that achieve the threshold value of ≥0.35 μg/mL will be assessed.
• Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs of Each Serotype Contained in V114: 30 Days PTD [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific OPA for all the 15 serotypes contained in V114. The OPA GMT for each serotype will be assessed.
• Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype Contained in V114: 30 Days PTD [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific OPA for the antigens contained in V114. The percentage of participants that achieve the GMT response threshold value will be assessed for each serotype.
• Percentage of Participants Who Meet Serotype-specific IgG Threshold Value IgG Threshold Value of ≥0.35 μg/mL for 2 Unique Serotypes Contained in V114 at 30 Days PTD [ Time Frame: 30 days PTD (Postdose 3 for full-term infants; Postdose 4 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for the 2 unique serotypes using PnECL. The percentage of participants that achieve the threshold value of ≥0.35 μg/mL will be assessed.

Original Secondary Outcome Measures (submitted: July 22, 2019)

• Percentage of Participants Who Meet Antigen-Specific Threshold Value for Each Antigen in Infanrix™ Hexa: 30 Days PTD [ Time Frame: 30 days PTD ]
  Sera from participants will be used to measure vaccine-induced antibodies for the antigens contained in Infanrix. The percentage that achieve the antigen-specific threshold value will be assessed.
• Anti-rotavirus Immunoglobulin A (IgA) Geometric Mean Titers (GMTs) of Rotarix™ [ Time Frame: 30 days post primary series (PPS; Postdose 2 for fullterm infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced antibodies (Immunoglobin A; [IgA]) for the antigens contained in Rotarix™. The GMT for each antigen contained in Rotarix™ will be assessed.
• Anti-PnPs Serotype-specific IgG Geometric Mean Concentrations (GMCs) for Each Serotype Contained in V114: 30 days Post Primary Series (PPS) [ Time Frame: 30 days PPS; (Postdose 2 for full-term infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using PnECL. The GMC for each serotype contained in V114 will be assessed.
• Percentage of Participants Who Meet Serotype-specific Immunoglobin G (IgG) Threshold Value of ≥0.35 μg/mL for Each Serotype Contained in V114; 30 Days PPS [ Time Frame: 30 days PPS (Postdose 2 for full-term infants; Postdose 3 for preterm infants) ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific IgG for all the 15 serotypes using pneumococcal PnECL. The percentage that achieve the GMC threshold value of ≥0.35 μg/mL will be assessed.
• Anti-PnPs Serotype-specific Opsonophagocytic Activity (OPA) GMTs of Each Serotype Contained in V114: 30 days PTD [ Time Frame: 30 days post PTD ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific OPA for all the 15 serotypes contained in V114. The OPA GMT for each serotype will be assessed.
• Percentage of Participants Who Meet Serotype-specific OPA Threshold Value for Each Serotype Contained in V114: 30 days PTD [ Time Frame: 30 days PTD ]
  Sera from participants will be used to measure vaccine-induced anti-PnPs serotype-specific OPA for the antigens contained in V114. The percentage that achieve the GMT response threshold value will be assessed for each serotype.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-025)
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Active-comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (PNEU-PED-EU-1)
• Brief Summary: This study will evaluate the safety and tolerability and immunogenicity of V114 when administered to 2-month old infants. The primary hypotheses are: 1) V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes between V114 and Prevenar 13™ based on response rates at 30 days post toddler dose (PTD); 2) V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on the response rates at 30 days PTD; 3) V114 is non-inferior to Prevenar 13™ for the 13 shared serotypes between V114 and Prevenar 13™ based on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobin G (IgG) geometric mean concentrations (GMCs) at 30 days PTD; and 4) V114 is superior to Prevenar 13™ for the 2 serotypes unique to V114 based on anti-PnPs serotype-specific IgG GMCs at 30 days PTD.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Pneumococcal Infections

Intervention

• Drug: Rotarix™
  Single 1.5 mL oral dose at 2 and 4 months of age (Study Day 1 and Month 2)
• Drug: Infanrix™ hexa
  Single 0.5 mL intramuscular injection at 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13)
• Drug: V114
  15-valent pneumococcal conjugate vaccine (PCV) containing 13 serotypes present in Prevenar 13™ (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and 2 unique serotypes (22F and 33F) in each 0.5 mL intramuscular administration,
  Other Names:

  • VAXNEUVANCE™
  • Pneumococcal 15-Valent Conjugate Vaccine
• Drug: Prevenar 13™
  13-valent PCV containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in each 0.5 mL intramuscular administration.

Study Arms

• Experimental: V114
  Full-term infants received a 0.5 mL intramuscular injection of V114 at approximately 2, 4, and 11-15 months of age (Study Day 1, Month 2, and Month 9-13). Preterm infants received a 0.5 mL intramuscular injection of V114 at approximately 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13). All infants also received intramuscular injection of 0.5 mL Infanrix™ hexa at approximately 2, 3, 4, and 11-15 months of age and 1.5 mL oral dose of Rotarix™ at 2 and 4 months of age.
  Interventions:

  • Drug: Rotarix™
  • Drug: Infanrix™ hexa
  • Drug: V114
• Active Comparator: Prevenar 13™
  Full-term infants received a 0.5 mL intramuscular injection of Prevenar 13™ at approximately 2, 4, and 11-15 months of age (Study Day 1, Month 2, and Month 9-13). Preterm infants received a 0.5 mL intramuscular injection of Prevenar 13™ at approximately 2, 3, 4, and 11-15 months of age (Study Day 1, Month 1, Month 2, and Month 9-13). All infants also received intramuscular injection of 0.5 mL Infanrix™ hexa at approximately 2, 3, 4, and 11-15 months of age and 1.5 mL oral dose of Rotarix™ at 2 and 4 months of age.
  Interventions:

  • Drug: Rotarix™
  • Drug: Infanrix™ hexa
  • Drug: Prevenar 13™

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 1, 2021): 1184
• Original Estimated Enrollment (submitted: July 22, 2019): 1180
• Actual Study Completion Date: August 5, 2021
• Actual Primary Completion Date: August 5, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

• Healthy
• Has a legally acceptable representative who understands the study procedures, alternate treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent

Exclusion Criteria

• History of invasive pneumococcal disease [(IPD); positive blood culture, positive cerebrospinal fluid culture, or other sterile site] or known history of other culture positive pneumococcal disease
• Has a known or suspected impairment of immunological function
• Has a history of congenital or acquired immunodeficiency
• Has, or his/her mother has, a documented human immunodeficiency virus (HIV) infection
• Has, or his/her mother has, a documented hepatitis B surface antigen - positive test
• Has known or history of functional or anatomic asplenia
• Has failure to thrive based on the clinical judgement of the Investigator
• Has a bleeding disorder contraindicating intramuscular vaccination
• Has a history of autoimmune disease (including but not limited to systemic lupus erythematosus, antiphospholipid syndrome, Behcet's disease, autoimmune thyroid disease, polymyositis and dermatomyositis, scleroderma, Type 1 diabetes mellitus, or other autoimmune disorders)
• Has a known neurologic or cognitive behavioral disorder, including encephalitis/myelitis, acute disseminating encephalomyelitis, pervasive development disorder, and related disorders
• Has received a dose of any pneumococcal vaccine prior to study entry
• Has received >1 dose of monovalent hepatitis B vaccine or hepatitis B-based combination vaccine prior to study entry
• Has received a dose of any acellular pertussis- or whole cell pertussis-based combination vaccines, Haemophilus influenzae type b conjugate vaccine, poliovirus vaccine, rotavirus vaccine, or any other combination thereof, prior to study entry
• Has received a blood transfusion or blood products, including immunoglobulins
• Has participated in another clinical study of an investigational product before the beginning or anytime during the duration of the current clinical study. Participants enrolled in observational studies may be included; these will be reviewed on a case-by-case basis for approval by the Sponsor
• Is or has an immediate family member (eg, parent/legal guardian or sibling) who is investigational site or Sponsor staff directly involved with this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 42 Days to 90 Days (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Czechia, Estonia, Germany, Greece, Poland, Russian Federation, Spain

Administrative Information

• NCT Number: NCT04031846
• Other Study ID Numbers: V114-025; 2018-003787-31 ( EudraCT Number ); V114-025 ( Other Identifier: Merck, Sharp & Dohme )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme LLC
• Study Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: December 2021