Lot-to-Lot Consistency of V114 in Healthy Adults (V114-020) (PNEU-TRUE)

A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled, Lot-to-Lot Consistency Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-TRUE)

The primary objectives are to evaluate the safety and tolerability of V114 and to compare the serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) across 3 different lots of V114. The primary hypothesis is that all 3 lots of V114 are equivalent as measured by the serotype-specific OPA GMTs for 15 serotypes in V114 at 30 days postvaccination.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections; Pneumonia, Pneumococcal
• Intervention / Treatment: Drug: V114; Drug: Prevnar 13™

• Study Type: Interventional
• Enrollment (Actual): 2340
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 6006)
    • Maroubra, New South Wales, Australia, 2035
      • Australian Clinical Research Network ( Site 6000)
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital ( Site 6001)
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Trialswest ( Site 6004)
• Chile
  • Santiago, Chile, 7500691
    • Instituto Nacional del Torax ( Site 2004)
  • Santiago, Chile, 8330034
    • Centro de Investigacion Clinica UC CICUC ( Site 2001)
  • Temuco, Chile, 4781151
    • Hospital Dr. Hernan Henriquez Aravena ( Site 2003)
  • RM
    • Santiago, RM, Chile, 9350079
      • CESFAM Colina ( Site 2002)
  • Región Metropolitana
    • Santiago, Región Metropolitana, Chile, 7650568
      • Clinica Alemana de Santiago Adolescencia ( Site 2000)
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital ( Site 3003)
  • Aarhus N, Denmark, 8200
    • Aarhus Universitets hospital ( Site 3004)
  • Ballerup, Denmark, 2750
    • CCBR. Center for Clinical and Basic Research ( Site 3000)
  • Copenhagen, Denmark, 2100
    • Rigshospitalet ( Site 3005)
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital ( Site 3002)
  • Odense, Denmark, 5000
    • Odense Universitetshospital ( Site 3001)
• Finland
  • Helsinki, Finland, 00100
    • Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 4006)
  • Jarvenpaa, Finland, 04400
    • Jarvenpaan rokotetutkimuskeskus ( Site 4005)
  • Kokkola, Finland, 67100
    • Kokkolan rokotetutkimusklinikka ( Site 4002)
  • Oulu, Finland, 90220
    • Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 4001)
  • Pori, Finland, 28100
    • Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 4004)
  • Tampere, Finland, 33100
    • Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 4000)
  • Turku, Finland, 20520
    • Turun rokotetutkimuskeskus ( Site 4003)
• United Kingdom
  • Harrow, United Kingdom, HA2 0RQ
    • GP Direct ( Site 5000)
  • Liverpool, United Kingdom, L5 8XR
    • Vauxhall Primary Health Care ( Site 5002)
  • Northamptonshire
    • Corby, Northamptonshire, United Kingdom, NN17 2UR
      • Medinova Lakeside Dedicated Research Centre ( Site 5004)
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus Clinical Research US, Inc. ( Site 1031)
    • Mesa, Arizona, United States, 85206
      • Synexus ( Site 1043)
  • California
    • Fountain Valley, California, United States, 92708
      • Southland Clinical Research Center ( Site 1027)
    • Northridge, California, United States, 91325
      • Valley Clinical Trials Inc. ( Site 1003)
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC ( Site 1019)
    • San Diego, California, United States, 92123
      • California Research Foundation ( Site 1006)
    • San Marcos, California, United States, 92078
      • Artemis Institute for Clinical Research ( Site 1041)
    • Simi Valley, California, United States, 93065
      • Alta California Medical Group ( Site 1020)
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Alliance for Multispecialty Research, LLC ( Site 1029)
    • DeLand, Florida, United States, 32720
      • Accel Research Sites-DeLand Clinical Research Unit ( Site 1026)
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research ( Site 1014)
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute ( Site 1012)
    • Miami, Florida, United States, 33186
      • Alpha Science Research ( Site 1015)
    • South Miami, Florida, United States, 33143
      • QPS Miami Research Associates ( Site 1035)
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research ( Site 1040)
  • Maryland
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group ( Site 1010)
  • Massachusetts
    • Marlborough, Massachusetts, United States, 01752
      • Community Clinical Research Network (Marlboro, MA) ( Site 1025)
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Wake Research Clinical Research Center of Nevada, LLC ( Site 1044)
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center ( Site 1011)
  • New York
    • Corning, New York, United States, 14830
      • Corning Center For Clinical Research ( Site 1033)
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc. ( Site 1024)
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc. ( Site 1039)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston Salem ( Site 1037)
  • Oklahoma
    • Lindsay, Oklahoma, United States, 73052
      • Unity Clinical Research ( Site 1036)
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center ( Site 1034)
  • Texas
    • Allen, Texas, United States, 75013
      • Wellness Clinical Research Associates ( Site 1038)
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group ( Site 1042)
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus ( Site 1000)
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research ( Site 1028)
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Allegiance Research Specialists ( Site 1013)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant has good health in the opinion of the investigator. Any underlying chronic condition must be documented to be in stable condition according to the investigator's judgment.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Female participant is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to use agreed upon contraception during the treatment period and for at least 6 weeks after the last dose of study intervention.

Exclusion Criteria:

• History of invasive pneumococcal disease (IPD) (positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1).
• Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine.
• Known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease.
• Coagulation disorder contraindicating intramuscular vaccinations.
• Recent febrile illness (defined as oral or tympanic temperature ≥100.4°F [≥38.0°C] or axillary or temporal temperature ≥99.4°F [≥37.4°C]) or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of study vaccine.
• History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• A WOCBP who has a positive urine or serum pregnancy test before the first vaccination at Visit 1 (Day 1).
• Has received any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside of the protocol.
• Has received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention at least 30 days before study entry.
• Has received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination. (Note: Topical, ophthalmic, intra-articular or soft-tissue [e.g., bursa, tendon steroid injections], and inhaled/nebulized steroids are permitted).
• Is receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease.
• Has received any non-live vaccine within the 14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine within 30 days following receipt of any study vaccine. (Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of any study vaccine or at least 15 days after receipt of any study vaccine.)
• Has received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days following receipt of any study vaccine. If this exclusion criterion is met, then Day 1 Visit may be rescheduled for a time when criterion is not met.
• Has received a blood transfusion or blood products, including immunoglobulin, within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion.
• Currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study.
• In the opinion of the investigator, has a history of clinically relevant drug or alcohol use that would interfere with participation in protocol-specified activities.
• History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114 Lot 1; Single intramuscular (IM) dose at 0.5 mL of V114 Lot 1 pneumococcal conjugate vaccine at Visit 1 (Day 1)	Drug: V114; 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.
Experimental: V114 Lot 2; Single IM dose at 0.5 mL of V114 Lot 2 pneumococcal conjugate vaccine at Visit 1 (Day 1)	Drug: V114; 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.
Experimental: V114 Lot 3; Single IM dose at 0.5 mL of V114 Lot 3 pneumococcal conjugate vaccine at Visit 1 (Day 1)	Drug: V114; 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.
Active Comparator: Prevnar 13™; Single IM dose at 0.5 mL of Prevnar 13™ at Visit 1 (Day 1)	Drug: Prevnar 13™; 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F in each 0.5. mL dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination With Separate V114 Lots	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consisted of redness/erythema, swelling, and tenderness/pain. The 95% confidence interval (CI) were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with solicited injection-site AEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.	Up to Day 5
Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consisted of redness/erythema, swelling, and tenderness/pain. Per the statistical analysis plan, within-group CIs were not calculated.	Up to Day 5
Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With Separate V114 Lots	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs consisted of muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. The 95% CI were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with solicited systemic AEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.	Up to Day 14
Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs consisted of muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. Per the statistical analysis plan, within-group CIs were not calculated.	Up to Day 14
Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With Separate V114 Lots	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. Relatedness of an SAE to the study vaccine is determined by the investigator. The 95% CI were based on the exact binomial method proposed by Clopper and Pearson. Following vaccination with the three lots of V114 the percentage of participants with SAEs was assessed. Per the statistical analysis plan, the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.	Up to Month 6
Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™	A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. Relatedness of an SAE to the study vaccine is determined by the investigator. Per the statistical analysis plan, within-group CIs were not calculated.	Up to Month 6
Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Following Vaccination With Separate V114 Lots	Opsonization of pneumococci for phagocytosis is an important mechanism by which antibodies to polysaccharides protect against disease in vivo. Sera from participants was used to measure geometric mean titer (GMT) of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, using the Multiplexed Opsonophagocytic Assay (MOPA). Per the statistical analysis plan, within-group CIs were not calculated. 95% CIs were calculated for the GMT ratios between pairs of V114 lots by a constrained longitudinal data analysis (cLDA) model; and the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) Following Vaccination With Separate V114 Lots	The geometric mean concentration (GMC) of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by multiplex electrochemiluminescence (ECL) using the pneumococcal electrochemiluminescence (PnECL) v2.0 assay. Per the statistical analysis plan, within-group CIs were not calculated; and the Prevnar 13™ treatment group was not included as it was not analyzed with the same approach as the separate V114 lots.	Day 30
Geometric Mean Concentration of Serotype-specific IgG Following Vaccination: Combined Lots of V114 or Prevnar 13™	The GMC of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. Per the statistical analysis plan, within-group CIs were not calculated,	Day 30
Geometric Mean Fold Rise (GMFR) in Serotype-specific OPA Following Vaccination With Separate V114 Lots	Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, using the MOPA which reads the reciprocal of the highest dilution that gives ≥50% bacterial killing. The Geometric Mean Fold Rise (GMFR) is the geometric mean of the ratio Day 30/Day 1 OPA responses. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.	Day 1 (Baseline) and Day 30
GMFR in Serotype-specific IgG Following Vaccination With Separate V114 Lots	The geometric mean concentration (GMC) of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. The GMFR is the geometric mean of the ratio Day 30/Day 1 IgG concentration. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.	Day 1 (Baseline) and Day 30
Percentage of Participants With ≥4 Fold Change in Serotype-specific OPA Following Vaccination With Separate V114 Lots	Sera from participants was used to measure GMT of 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) included in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, with the MOPA which reads the reciprocal of the highest dilution (1/dil) that gives ≥50% bacterial killing. Percentage of participants with a ≥ 4-fold change from Day 1 (baseline) to Day 30 (Day 30/Day 1) are presented. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.	Day 1 (Baseline) and Day 30
Percentage of Participants With ≥4 Fold Change in Serotype-specific IgG Following Vaccination With Separate V114 Lots	The geometric mean concentration of IgG serotype-specific antibodies to the 13 pneumococcal polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) contained in V114 and Prevnar 13™; and two serotypes (22F and 33F) which are unique to V114, were quantitated from participants' sera by ECL. Percentage of participants with a ≥ 4-fold change from Day 1 (baseline) to Day 30 (Day 30/ Day 1) are presented. Per the statistical analysis plan, the Prevnar 13™ treatment group was not analyzed.	Day 1 (Baseline) and Day 30

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Simon JK, Staerke NB, Hemming-Harlo M, Layle S, Dagan R, Shekar T, Pedley A, Jumes P, Tamms G, Sterling T, Musey L, Buchwald UK; V114-020 PNEU-TRUE study group. Lot-to-lot consistency, safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in healthy adults aged >/=50 years: A randomized phase 3 trial (PNEU-TRUE). Vaccine. 2022 Feb 23;40(9):1342-1351. doi: 10.1016/j.vaccine.2021.12.067. Epub 2022 Jan 14.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2019
• Primary Completion (Actual): April 3, 2020
• Study Completion (Actual): April 3, 2020

Study Registration Dates

• First Submitted: May 13, 2019
• First Submitted That Met QC Criteria: May 13, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-020 (Other Identifier: Merck); 2018-004266-33 (Other Identifier: EudraCT Number)

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