20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study in Healthy Japanese Infants

• ClinicalTrials.gov Identifier: NCT04530838
• Recruitment Status: Completed
• First Posted: August 28, 2020
• Results First Posted: April 21, 2023
• Last Update Posted: April 21, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 25, 2020
• First Posted Date: August 28, 2020
• Results First Submitted Date: March 30, 2023
• Results First Posted Date: April 21, 2023
• Last Update Posted Date: April 21, 2023
• Actual Study Start Date: September 16, 2020
• Actual Primary Completion Date: April 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2023)

• Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 [ Time Frame: Within 7 Days after Dose 1 ]
  Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 centimeter (cm). Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm.
• Percentage of Participants With Local Reactions Within 7 Days After Dose 2 [ Time Frame: Within 7 Days after Dose 2 ]
  Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm.
• Percentage of Participants With Local Reactions Within 7 Days After Dose 3 [ Time Frame: Within 7 Days after Dose 3 ]
  Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm.
• Percentage of Participants With Local Reactions Within 7 Days After Dose 4 [ Time Frame: Within 7 Days after Dose 4 ]
  Local reactions included pain at injection site, redness and swelling were measured and recorded in measuring device (caliper) units. 1 measuring device unit =0.5 cm. Pain at injection site was graded as mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: limited limb movement. Redness and swelling were graded as mild: >0 to 2.0 cm; moderate >2.0 to 7.0 cm; and severe: >7.0 cm.
• Percentage of Participants With Systemic Events Within 7 Days After Dose 1 [ Time Frame: Within 7 Days After Dose 1 ]
  Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature greater than or equal to (>=) 37.5 degree Celsius (C), and categorized as >=37.5 to 38.4 degree C, greater than (>)38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted).
• Percentage of Participants With Systemic Events Within 7 Days After Dose 2 [ Time Frame: Within 7 Days After Dose 2 ]
  Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted).
• Percentage of Participants With Systemic Events Within 7 Days After Dose 3 [ Time Frame: Within 7 Days After Dose 3 ]
  Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted).
• Percentage of Participants With Systemic Events Within 7 Days After Dose 4 [ Time Frame: Within 7 Days After Dose 4 ]
  Systemic events included fever, decreased appetite, drowsiness and irritability. Fever was defined as an axillary temperature >=37.5 degree C and categorized as >=37.5 to 38.4 degree C,>38.4 to 38.9 degree C,>38.9 to 40.0 degree C and >40.0 degree C; decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed); drowsiness was graded as mild (increased or prolonged sleeping bouts), moderate (slightly subdued, interfered with daily activity) and severe (disabling, not interested in usual daily activity); Irritability: graded as mild (easily consolable), moderate (required increased attention) and severe (inconsolable, crying could not be comforted).
• Percentage of Participants With Adverse Events (AEs) From Dose 1 to 1 Month After Dose 3 [ Time Frame: Day 1 of Dose 1 to 1 Month after Dose 3 ]
  An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
• Percentage of Participants With AEs From Dose 4 to 1 Month After Dose 4 [ Time Frame: From Dose 4 to 1 Month after Dose 4 ]
  An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
• Percentage of Participants With Serious Adverse Events (SAEs) From Dose 1 to 1 Month After Dose 4 [ Time Frame: From Dose 1 to 1 Month after Dose 4 ]
  A serious AE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events.
• Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) From Dose 1 to 1 Month After Dose 4 [ Time Frame: From Dose 1 to 1 Month after Dose 4 ]
  An NDCMC was defined as a significant disease or medical condition, not previously identified, that is expected to be persistent or was otherwise long-lasting in its effects.
• Percentage of Participants With Predefined Pneumococcal Serotype-specific Immunoglobulin G (IgG) Concentrations 1 Month After Dose 3 [ Time Frame: 1 Month after Dose 3 ]
  Pneumococcal serotype-specific IgG Concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ. The predefined levels, >=0.35 micrograms/mL for all serotypes except for serotypes 5 (>=0.23 micrograms/mL), 6B (>=0.10 micrograms/mL) and 19A (>=0.12 micrograms/mL).

Original Primary Outcome Measures (submitted: August 25, 2020)

• The percentages of participants reporting prompted local reactions within 7 days after each vaccination in each group [ Time Frame: 7 days ]
  Prompted local reactions after each dose
• The percentages of participants reporting prompted systemic events within 7 days after each vaccination in each group [ Time Frame: 7 days ]
  Prompted systemic events after each dose
• The percentages of participants reporting AEs from Dose 1 to 1 month after Dose 3 in each group [ Time Frame: Dose 1 to 1 month after Dose 3 ]
  Adverse events occurring from Dose 1 to 1 month after Dose 3
• The percentages of participants reporting AEs from Dose 4 to 1 month after Dose 4 in each group [ Time Frame: Dose 4 to 1 month after Dose 4 ]
  Adverse events occurring from Dose 4 to 1 month after Dose 4
• The percentages of participants reporting SAEs up to 1 month after Dose 4 in each group [ Time Frame: Dose 1 to 1 month after Dose 4 ]
  SAEs occurring up to 1 month after Dose 4
• The percentages of participants reporting NDCMCs up to 1 month after Dose 4 in each group [ Time Frame: Dose 1 to 1 month after Dose 4 ]
  NDCMCs occurring up to 1 month after Dose 4
• The percentages of participants with pre-defined pneumococcal IgG concentrations at 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  IgG concentrations 1 month after Dose 3

Current Secondary Outcome Measures (submitted: March 30, 2023)

• Geometric Mean Concentration of Pneumococcal Serotype-Specific IgG Concentrations 1 Month After Dose 3 [ Time Frame: 1 Month after Dose 3 ]
  Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. Assay results below the LLOQ were set to 0.5*LLOQ.
• Geometric Mean Concentration of Pneumococcal Serotype-Specific IgG Concentrations 1 Month After Dose 4 [ Time Frame: 1 Month after Dose 4 ]
  Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F.
• Geometric Mean Titer (GMTs) of Serotype Specific Opsonophagocytic Activity (OPA) at 1 Month After Dose 3, Before Dose 4 and 1 Month After Dose 4 [ Time Frame: 1 Month after Dose 3, before Dose 4 and 1 Month after Dose 4 ]
  20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. OPA titers were determined in randomly selected subsets of sera from each vaccine group.
• Percentage of Participants With Pre-defined Pneumococcal Serotype-specific IgG Concentrations at 1 Month After Dose 4 [ Time Frame: 1 Month after Dose 4 ]
  Pneumococcal serotype-specific IgG concentrations were measured for 20vPnC serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The predefined levels, >=0.35 micrograms/mL for all serotypes except for serotypes 5 (>=0.23 micrograms/mL), 6B (>=0.10 micrograms/mL) and 19A (>=0.12 micrograms/mL).
• Geometric Mean Fold Rise (GMFR) in Serotype-Specific IgG Concentrations From 1 Month After Dose 3 to Before Dose 4 [ Time Frame: 1 Month after Dose 3 to before Dose 4 ]
  GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from 1 month after Dose 3 to before Dose 4 was reported from participants in Dose 3 evaluable immunogenicity population.
• GMFR in Serotype-Specific IgG Concentrations From 1 Month After Dose 3 to 1 Month After Dose 4 [ Time Frame: From 1 Month after Dose 3 to 1 Month after Dose 4 ]
  GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from 1 month after Dose 3 to 1 month after Dose 4 was reported from participants in both the Dose 3 and Dose 4 evaluable immunogenicity population.
• GMFR in Serotype-Specific IgG Concentrations From Before Dose 4 to 1 Month After Dose 4 [ Time Frame: From before Dose 4 to 1 Month after Dose 4 ]
  GMFR of pneumococcal 20vPnC serotypes included: 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F. The GMFR from before Dose 4 to 1 month after Dose 4 was reported from participants in the Dose 4 evaluable immunogenicity population.

Original Secondary Outcome Measures (submitted: August 25, 2020)

• IgG GMCs 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  IgG GMCs 1 month after Dose 3
• The percentages of participants with pre-defined pneumococcal IgG concentrations at 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  IgG concentrations 1 month after Dose 4
• IgG GMCs 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  IgG GMCs 1 month after Dose 4
• OPA GMTs 1 month after Dose 3 [ Time Frame: 1 month after Dose 3 ]
  OPA GMTs 1 month after Dose 3
• OPA GMTs 1 month after Dose 4 [ Time Frame: 1 month after Dose 4 ]
  OPA GMTs 1 month after Dose 4
• IgG GMFRs from 1 month after Dose 3 to before Dose 4 [ Time Frame: From 1 month after Dose 3 to before Dose 4 ]
  IgG GMFRs from 1 month after Dose 3 to before Dose 4
• IgG GMFRs from before Dose 4 to 1 month after Dose 4 [ Time Frame: From before Dose 4 to 1 month after Dose 4 ]
  IgG GMFRs from before Dose 4 to 1 month after Dose 4
• IgG GMFRs from 1 month after Dose 3 to 1 month after Dose 4 [ Time Frame: From 1 month after Dose 3 to 1 month after Dose 4 ]
  IgG GMFRs from 1 month after Dose 3 to 1 month after Dose 4

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

Descriptive Information

• Brief Title: 20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study in Healthy Japanese Infants
• Official Title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, THIRD PARTY UNBLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY JAPANESE INFANTS
• Brief Summary: 20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study in Healthy Japanese Infants
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Pneumococcal Disease

Intervention

• Biological: 20-valent pneumococcal conjugate vaccine
  20-valent pneumococcal conjugate vaccine
• Biological: 13-valent pneumococcal conjugate vaccine
  13-valent pneumococcal conjugate vaccine

Study Arms

• Experimental: 20-valent pneumococcal conjugate vaccine (subcutaneous)
  20-valent pneumococcal conjugate vaccine administered by subcutaneous injection (SC)
  Intervention: Biological: 20-valent pneumococcal conjugate vaccine
• Active Comparator: 13-valent pneumococcal conjugate vaccine (subcutaneous)
  13-valent pneumococcal conjugate vaccine administered by subcutaneous injection (SC)
  Intervention: Biological: 13-valent pneumococcal conjugate vaccine
• Experimental: 20-valent pneumococcal conjugate vaccine (intramuscular)
  20-valent pneumococcal conjugate vaccine administered by intramuscular injection (IM)
  Intervention: Biological: 20-valent pneumococcal conjugate vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 1, 2021): 668
• Original Estimated Enrollment (submitted: August 25, 2020): 666
• Actual Study Completion Date: April 2, 2022
• Actual Primary Completion Date: April 2, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Japanese male or female infants ≥2 months to ≤6 months at the time of consent.
• Healthy infants determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study.

Exclusion Criteria:

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis)
• Major known congenital malformation or serious chronic disorder.
• History of microbiologically proven invasive disease caused by S pneumoniae.
• Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Months to 6 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04530838
• Other Study ID Numbers: B7471016; 2022-001146-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2023