Trial to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine-naïve Adults

A PHASE 3, RANDOMIZED, DOUBLE-BLIND TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF A 20-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN PNEUMOCOCCAL VACCINE-NAÏVE ADULTS 18 YEARS OF AGE AND OLDER

A Phase 3, Randomized, Double-Blind Trial to Evaluate the Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine-Naïve Adults

Study Overview

• Status: Completed
• Conditions: Pneumococcal Disease
• Intervention / Treatment: Other: Saline; Biological: 20vPnC; Biological: 13vPnC; Biological: PPSV23

• Study Type: Interventional
• Enrollment (Actual): 3902
• Phase: Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Boras, Sweden, 50630
    • Ladulaas Kliniska Studier
  • Eskilstuna, Sweden, 63188
    • Infektionskliniken Malarsjukhuset
  • Lund, Sweden, 222 22
    • ProbarE i Lund
  • Stockholm, Sweden, 113 61
    • Karolinska Trial Alliance, KTA Prim
  • Stockholm, Sweden, 114 46
    • Akardo Med Site
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset
  • Örebro, Sweden, 70362
    • Avdelningen för kliniska prövningar
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Accel Research Sites
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Chandler, Arizona, United States, 85224
      • East Valley Gastroenterology and Hepatology Associates
    • Peoria, Arizona, United States, 85381
      • The Pain Center of Arizona
    • Phoenix, Arizona, United States, 85015
      • MedPharmics, LLC
    • Phoenix, Arizona, United States, 85018
      • HOPE Research Institute
    • Phoenix, Arizona, United States, 85018
      • The Pain Center of Arizona
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting, LLC
  • Florida
    • Crystal River, Florida, United States, 34429
      • Nature Coast Clinical Research
    • DeLand, Florida, United States, 32720
      • Accel Research Sites - Clinical Research Unit
    • Hollywood, Florida, United States, 33024
      • Research Centers of America, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research LLC
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Kansas
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC
    • Newton, Kansas, United States, 67114
      • Axtell Clinic, P.A.
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
    • Wichita, Kansas, United States, 67205
      • Northwest Family Physicians
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Meridian Clinical Research, LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research LLC
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research, Inc.
  • New York
    • Binghamton, New York, United States, 13901
      • United Medical Associates
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45206
      • Cincinnati Children's Hospital Medical Center
    • Cincinnati, Ohio, United States, 45246
      • Sterling Research Group, Ltd.
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center (CCHMC)
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research, LLC
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc.
    • Bellaire, Texas, United States, 77401
      • Bellaire Doctor's Clinic
    • Fort Worth, Texas, United States, 76104
      • Ventavia Research Group, LLC
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • Fort Worth, Texas, United States, 76135
      • HealthFirst Medical Group
    • Keller, Texas, United States, 76248
      • Ventavia Research Group, LLC
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • Spring, Texas, United States, 77389
      • Ventavia Research Group, LLC
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Draper, Utah, United States, 84020
      • J. Lewis Research Inc. / Foothill Family Clinic Draper
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc. - Jordan River Family Medicine
  • Washington
    • Seattle, Washington, United States, 98101
      • Kaiser Permanente Washington Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female adults >/= 18 years of age (from the 18th birthday) at enrollment and older.
2. Adults determined by clinical assessment, including medical history and clinical judgment, to be eligible for the study, including adults with preexisting stable disease, defined as disease not requiring significant change in therapy in the previous 6 weeks or hospitalization for worsening disease within 12 weeks before receipt of investigational product.
3. Negative urine pregnancy test at Visit1 for all subjects who are of childbearing potential.

Exclusion Criteria:

1. Previous vaccination with any licensed or investigational pneumococcal vaccine, or planned receipt through study participation.
2. History of microbiologically proven invasive disease caused by S pneumoniae.
3. Serious chronic disorder including metastatic malignancy, severe chronic obstructive pulmonary disease (COPD) requiring supplemental oxygen, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that, in the investigator's opinion, excludes the subject from participating in the study.
4. Pregnant female subjects or breastfeeding female subjects.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 60 years and above 20vPnC/Saline; 20vPnC and saline	Other: Saline; Placebo; Biological: 20vPnC; 20vPnC
Active Comparator: 60 years and above 13vPnC/PPSV23; 13vPnC and PPSV23	Biological: 13vPnC; Pneumococcal conjugate vaccine; Biological: PPSV23; Pneumococcal polysaccharide vaccine; Other Names: Pneumovax 23
Experimental: 50 through 59 years of age 20vPnC; 20vPnC	Biological: 20vPnC; 20vPnC
Experimental: 18 through 49 years of age 20vPnC; 20vPnC	Biological: 20vPnC; 20vPnC
Active Comparator: 50 through 59 years of age 13vPnC; 13vPnC	Biological: 13vPnC; Pneumococcal conjugate vaccine
Active Comparator: 18 through 49 years of age 13vPnC; 13vPnC	Biological: 13vPnC; Pneumococcal conjugate vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Local Reactions Within 10 Days After Vaccination in All Cohorts	Local reactions were recorded using an electronic diary. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm). Redness and swelling were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm) and severe (>10.0 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).	Within 10 days after 20vPnC or 13vPnC
Percentage of Participants With Systemic Events Within 7 Days After Vaccination in All Cohorts	Systemic events fever, fatigue, headache, muscle pain and joint pain were recorded by using an electronic diary. Fever was defined as greater than or equal to (>=) 38.0 degree Celsius (C) and categorized to >=38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, muscle pain and joint pain were graded as mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity).	Within 7 days after 20vPnC or 13vPnC
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Vaccination in All Cohorts	An AE was any untoward medical occurrence in study participants who received study vaccine without regard to possibility of causal relationship with the treatment.	Within 1 month after 20vPnC or 13vPnC
Percentage of Participants With Serious Adverse Events (SAEs) Within 6 Months After Vaccination in All Cohorts	An SAE was any untoward medical occurrence at any dose that results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect or that is considered to be an important medical event.	Within 6 months after 20vPnC or 13vPnC
Percentage of Participants With Newly Diagnosed Chronic Medical Conditions (NDCMCs) Within 6 Months After Vaccination in All Cohorts	An NDCMC was defined as a disease or medical condition, not previously identified, that was expected to be persistent or was otherwise long-lasting in its effects.	Within 6 months after 20vPnC or 13vPnC
Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population	OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated.	1 month after Vaccination 1
Pneumococcal OPA GMTs for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population (E7-AIP)	OPA GMTs were determined for serotypes: 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated.	1 month after Vaccination 1 in "Cohort 1: 20vPnC/Saline"; 1 month after Vaccination 2 in "Cohort 1: 13vPnC/PPSV23"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 2, 50 Through 59 Years of Age and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population	OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated.	1 month after vaccination
Pneumococcal OPA GMTs for the 20 Vaccines Serotypes at 1 Month After 20vPnC Vaccination in Cohort 3, 18 Through 49 Years and Cohort 1, Only 60 Through 64 Years of Age: Evaluable-20 Immunogenicity Population	OPA GMTs were determined for serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. OPA titer was expressed as reciprocal of the highest serum dilution. OPA geometric mean and 2-sided 95% CIs were calculated.	1 month after vaccination
Pneumococcal OPA Geometric Mean Fold Rises (GMFRs) for the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population	OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.	Before Vaccination 1 to 1 month after Vaccination 1
Pneumococcal OPA GMFRs for the Additional 7 Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population	OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F.	From before Vaccination 1 to 1 month after Vaccination 1 in "Cohort 1: 20vPnC/Saline" or From before Vaccination 1 to 1 month after Vaccination 2 in "Cohort 1: 13vPnC/PPSV23"
Pneumococcal OPA GMFRs for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population	OPA GMFR is the ratio of OPA GMT, 1 month after vaccination to before vaccination OPA GMT. OPA GMFRs from before to 1 month after vaccination were calculated along with corresponding 2-sided 95% CIs for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F.	Before vaccination to 1 month after vaccination
Percentage of Participants With >=4-Fold Rise in Pneumococcal OPA Titers to the 13 Matched Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population	Percentage of participants with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.	Before Vaccination 1 to 1 month after Vaccination 1
Percentage of Participants With >=4-Fold Rise in Pneumococcal OPA Titers for the 7 Additional Serotypes From Before Vaccination 1 to 1 Month After Vaccination 1(20vPnC) or From Before Vaccination 1 to 1 Month After Vaccination 2(PPSV23) in Cohort 1:E7-AIP	Percentage of participants with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F.	Before Vaccination 1 to 1 month after Vaccination 1 for "Cohort 1: 20vPnC/Saline"; Before Vaccination 1 to 1 month after Vaccination 2 for "Cohort 1: 13vPnC/PPSV23"
Percentage of Participants With >=4-Fold Rise in Pneumococcal OPA Titers for the 20 Vaccines Serotypes From Before Vaccination to 1 Month After Vaccination in Cohort 2 and 3: Evaluable-20 Immunogenicity Population	Percentage of participants with a >=4-fold rise in serotype-specific pneumococcal OPA titers from before vaccination to 1 month after vaccination along with corresponding 2-sided 95% CIs were calculated for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F.	Before vaccination to 1 month after vaccination
Percentage of Participants With Pneumococcal OPA Titers >= Lower Limit of Quantitation (LLOQ) for the 13 Matched Serotypes at 1 Month After Vaccination 1 (20vPnC or 13vPnC) in Cohort 1: Evaluable 13-Matched Immunogenicity Population	The percentage of participants with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.	1 month after Vaccination 1
Percentage of Participants With Pneumococcal OPA Titers >=LLOQ for the 7 Additional Serotypes at 1 Month After Vaccination 1 (20vPnC) or 1 Month After Vaccination 2 (PPSV23) in Cohort 1: Evaluable 7-Additional Immunogenicity Population	The percentage of participants with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F.	1 month after Vaccination 1 in "Cohort 1: 20vPnC/Saline" or 1 month after Vaccination 2 in "Cohort 1: 13vPnC/PPSV23"
Percentage of Participants With Pneumococcal OPA Titers >=LLOQ for the 20 Vaccines Serotypes at 1 Month After Vaccination (20vPnC) in Cohort 2 and 3: Evaluable-20 Immunogenicity Population	The percentage of participants with OPA titers >=LLOQ along with corresponding 2-sided 95% CIs were calculated 1 month after vaccination for pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F, 8, 10A, 11A, 12F, 15B, 22F and 33F. Data for this outcome measure were planned to be analyzed for the 20vPnC groups of Cohorts 2 and 3 only.	1 month after vaccination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Sabharwal C, Sundaraiyer V, Peng Y, Moyer L, Belanger TJ, Gessner BD, Jodar L, Jansen KU, Gruber WC, Scott DA, Watson W. Immunogenicity of a 20-valent pneumococcal conjugate vaccine in adults 18 to 64 years old with medical conditions and other factors that increase risk of pneumococcal disease. Hum Vaccin Immunother. 2022 Nov 30;18(6):2126253. doi: 10.1080/21645515.2022.2126253. Epub 2022 Nov 11.
• Essink B, Sabharwal C, Cannon K, Frenck R, Lal H, Xu X, Sundaraiyer V, Peng Y, Moyer L, Pride MW, Scully IL, Jansen KU, Gruber WC, Scott DA, Watson W. Pivotal Phase 3 Randomized Clinical Trial of the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate Vaccine in Adults Aged >/=18 Years. Clin Infect Dis. 2022 Aug 31;75(3):390-398. doi: 10.1093/cid/ciab990.
• Mt-Isa S, Abderhalden LA, Musey L, Weiss T. Matching-adjusted indirect comparison of pneumococcal vaccines V114 and PCV20. Expert Rev Vaccines. 2022 Jan;21(1):115-123. doi: 10.1080/14760584.2021.1994858. Epub 2021 Oct 27.
• Perdrizet J, Santana CFS, Senna T, Alexandre RF, Sini de Almeida R, Spinardi J, Wasserman M. Cost-effectiveness analysis of replacing the 10-valent pneumococcal conjugate vaccine (PCV10) with the 13-valent pneumococcal conjugate vaccine (PCV13) in Brazil infants. Hum Vaccin Immunother. 2021 Apr 3;17(4):1162-1172. doi: 10.1080/21645515.2020.1809266. Epub 2020 Sep 23.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): December 16, 2019
• Study Completion (Actual): December 16, 2019

Study Registration Dates

• First Submitted: November 29, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 29, 2021
• Last Verified: November 1, 2021

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: B7471007; 2018-004279-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No