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

NCT03950856 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V114-0202018-004266-33
• Study Type: interventional
• Target: 2,340
• Locations: 6 countries
• Sites: 55

Brief Summary

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.

Conditions

Pneumococcal Infections; Pneumonia, Pneumococcal

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (6)

• Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) Following Vaccination With Separate V114 Lots

  Day 30

• Geometric Mean Concentration of Serotype-specific IgG Following Vaccination: Combined Lots of V114 or Prevnar 13™

  Day 30

• Geometric Mean Fold Rise (GMFR) in Serotype-specific OPA Following Vaccination With Separate V114 Lots

  Day 1 (Baseline) and Day 30

• GMFR in Serotype-specific IgG Following Vaccination With Separate V114 Lots

  Day 1 (Baseline) and Day 30

• Percentage of Participants With ≥4 Fold Change in Serotype-specific OPA Following Vaccination With Separate V114 Lots

  Day 1 (Baseline) and Day 30

Study Arms (4)

V114 Lot 1

EXPERIMENTAL

Single intramuscular (IM) dose at 0.5 mL of V114 Lot 1 pneumococcal conjugate vaccine at Visit 1 (Day 1)

Drug: V114

V114 Lot 2

EXPERIMENTAL

Single IM dose at 0.5 mL of V114 Lot 2 pneumococcal conjugate vaccine at Visit 1 (Day 1)

Drug: V114

V114 Lot 3

EXPERIMENTAL

Single IM dose at 0.5 mL of V114 Lot 3 pneumococcal conjugate vaccine at Visit 1 (Day 1)

Drug: V114

Prevnar 13™

ACTIVE COMPARATOR

Single IM dose at 0.5 mL of Prevnar 13™ at Visit 1 (Day 1)

Drug: Prevnar 13™

Interventions

V114 DRUG

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.

V114 Lot 1; V114 Lot 2; V114 Lot 3

Prevnar 13™ DRUG

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.

Prevnar 13™

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (55)

Synexus Clinical Research US, Inc. ( Site 1031)

Chandler, Arizona, 85224, United States

Location

Synexus ( Site 1043)

Mesa, Arizona, 85206, United States

Location

Southland Clinical Research Center ( Site 1027)

Fountain Valley, California, 92708, United States

Location

Valley Clinical Trials Inc. ( Site 1003)

Northridge, California, 91325, United States

Location

Center for Clinical Trials, LLC ( Site 1019)

Paramount, California, 90723, United States

Location

California Research Foundation ( Site 1006)

San Diego, California, 92123, United States

Location

Artemis Institute for Clinical Research ( Site 1041)

San Marcos, California, 92078, United States

Location

Alta California Medical Group ( Site 1020)

Simi Valley, California, 93065, United States

Location

Alliance for Multispecialty Research, LLC ( Site 1029)

Coral Gables, Florida, 33134, United States

Location

Accel Research Sites-DeLand Clinical Research Unit ( Site 1026)

DeLand, Florida, 32720, United States

Location

Jacksonville Center for Clinical Research ( Site 1014)

Jacksonville, Florida, 32216, United States

Location

L&C Professional Medical Research Institute ( Site 1012)

Miami, Florida, 33144, United States

Location

Alpha Science Research ( Site 1015)

Miami, Florida, 33186, United States

Location

QPS Miami Research Associates ( Site 1035)

South Miami, Florida, 33143, United States

Location

Benchmark Research ( Site 1040)

Metairie, Louisiana, 70006, United States

Location

Centennial Medical Group ( Site 1010)

Elkridge, Maryland, 21075, United States

Location

Community Clinical Research Network (Marlboro, MA) ( Site 1025)

Marlborough, Massachusetts, 01752, United States

Location

Wake Research Clinical Research Center of Nevada, LLC ( Site 1044)

Las Vegas, Nevada, 89104, United States

Location

Southwest CARE Center ( Site 1011)

Santa Fe, New Mexico, 87505, United States

Location

Corning Center For Clinical Research ( Site 1033)

Corning, New York, 14830, United States

Location

Regional Clinical Research, Inc. ( Site 1024)

Endwell, New York, 13760, United States

Location

Rochester Clinical Research, Inc. ( Site 1039)

Rochester, New York, 14609, United States

Location

PMG Research of Winston Salem ( Site 1037)

Winston-Salem, North Carolina, 27103, United States

Location

Unity Clinical Research ( Site 1036)

Lindsay, Oklahoma, 73052, United States

Location

Coastal Carolina Research Center ( Site 1034)

Mt. Pleasant, South Carolina, 29464, United States

Location

Wellness Clinical Research Associates ( Site 1038)

Allen, Texas, 75013, United States

Location

Diagnostics Research Group ( Site 1042)

San Antonio, Texas, 78229, United States

Location

Synexus ( Site 1000)

Murray, Utah, 84123, United States

Location

Advanced Clinical Research ( Site 1028)

West Jordan, Utah, 84088, United States

Location

Allegiance Research Specialists ( Site 1013)

Wauwatosa, Wisconsin, 53226, United States

Location

Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 6006)

Blacktown, New South Wales, 2148, Australia

Location

Australian Clinical Research Network ( Site 6000)

Maroubra, New South Wales, 2035, Australia

Location

Box Hill Hospital ( Site 6001)

Box Hill, Victoria, 3128, Australia

Location

Trialswest ( Site 6004)

Murdoch, Western Australia, 6150, Australia

Location

CESFAM Colina ( Site 2002)

Santiago, RM, 9350079, Chile

Location

Clinica Alemana de Santiago Adolescencia ( Site 2000)

Santiago, Santiago Metropolitan, 7650568, Chile

Location

Instituto Nacional del Torax ( Site 2004)

Santiago, 7500691, Chile

Location

Centro de Investigacion Clinica UC CICUC ( Site 2001)

Santiago, 8330034, Chile

Location

Hospital Dr. Hernan Henriquez Aravena ( Site 2003)

Temuco, 4781151, Chile

Location

Aalborg University Hospital ( Site 3003)

Aalborg, 9000, Denmark

Location

Aarhus Universitets hospital ( Site 3004)

Aarhus N, 8200, Denmark

Location

CCBR. Center for Clinical and Basic Research ( Site 3000)

Ballerup Municipality, 2750, Denmark

Location

Rigshospitalet ( Site 3005)

Copenhagen, 2100, Denmark

Location

Hvidovre Hospital ( Site 3002)

Hvidovre, 2650, Denmark

Location

Odense Universitetshospital ( Site 3001)

Odense, 5000, Denmark

Location

Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 4006)

Helsinki, 00100, Finland

Location

Jarvenpaan rokotetutkimuskeskus ( Site 4005)

Jarvenpaa, 04400, Finland

Location

Kokkolan rokotetutkimusklinikka ( Site 4002)

Kokkola, 67100, Finland

Location

Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 4001)

Oulu, 90220, Finland

Location

Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 4004)

Pori, 28100, Finland

Location

Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 4000)

Tampere, 33100, Finland

Location

Turun rokotetutkimuskeskus ( Site 4003)

Turku, 20520, Finland

Location

Medinova Lakeside Dedicated Research Centre ( Site 5004)

Corby, Northamptonshire, NN17 2UR, United Kingdom

Location

GP Direct ( Site 5000)

Harrow, HA2 0RQ, United Kingdom

Location

Vauxhall Primary Health Care ( Site 5002)

Liverpool, L5 8XR, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35039194 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections; Pneumonia, Pneumococcal

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 15, 2019
• Study Start: June 12, 2019
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• Last Updated: April 12, 2021
• Results First Posted: April 12, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (6); GB (3); CL (5); US (30); AU (4); FI (7)