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

Pneumococcal Infections Clinical Trial

— PNEU-TRUE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03950856
• Other study ID #: V114-020
• Secondary ID: V114-0202018-004
• Status: Completed
• Phase: Phase 3
• Start date: June 12, 2019
• Est. completion date: April 3, 2020

Study information

• Verified date: March 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2340
• Est. completion date: April 3, 2020
• Est. primary completion date: April 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections
• Pneumonia
• Pneumonia, Pneumococcal

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 6006)	Blacktown	New South Wales
Australia	Box Hill Hospital ( Site 6001)	Box Hill	Victoria
Australia	Australian Clinical Research Network ( Site 6000)	Maroubra	New South Wales
Australia	Trialswest ( Site 6004)	Murdoch	Western Australia
Chile	Centro de Investigacion Clinica UC CICUC ( Site 2001)	Santiago
Chile	CESFAM Colina ( Site 2002)	Santiago	RM
Chile	Clinica Alemana de Santiago Adolescencia ( Site 2000)	Santiago	Región Metropolitana
Chile	Instituto Nacional del Torax ( Site 2004)	Santiago
Chile	Hospital Dr. Hernan Henriquez Aravena ( Site 2003)	Temuco
Denmark	Aalborg University Hospital ( Site 3003)	Aalborg
Denmark	Aarhus Universitets hospital ( Site 3004)	Aarhus N
Denmark	CCBR. Center for Clinical and Basic Research ( Site 3000)	Ballerup
Denmark	Rigshospitalet ( Site 3005)	Copenhagen
Denmark	Hvidovre Hospital ( Site 3002)	Hvidovre
Denmark	Odense Universitetshospital ( Site 3001)	Odense
Finland	Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 4006)	Helsinki
Finland	Jarvenpaan rokotetutkimuskeskus ( Site 4005)	Jarvenpaa
Finland	Kokkolan rokotetutkimusklinikka ( Site 4002)	Kokkola
Finland	Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 4001)	Oulu
Finland	Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 4004)	Pori
Finland	Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 4000)	Tampere
Finland	Turun rokotetutkimuskeskus ( Site 4003)	Turku
United Kingdom	Medinova Lakeside Dedicated Research Centre ( Site 5004)	Corby	Northamptonshire
United Kingdom	GP Direct ( Site 5000)	Harrow
United Kingdom	Vauxhall Primary Health Care ( Site 5002)	Liverpool
United States	Wellness Clinical Research Associates ( Site 1038)	Allen	Texas
United States	Synexus Clinical Research US, Inc. ( Site 1031)	Chandler	Arizona
United States	Alliance for Multispecialty Research, LLC ( Site 1029)	Coral Gables	Florida
United States	Corning Center For Clinical Research ( Site 1033)	Corning	New York
United States	Accel Research Sites-DeLand Clinical Research Unit ( Site 1026)	DeLand	Florida
United States	Centennial Medical Group ( Site 1010)	Elkridge	Maryland
United States	Regional Clinical Research, Inc. ( Site 1024)	Endwell	New York
United States	Southland Clinical Research Center ( Site 1027)	Fountain Valley	California
United States	Jacksonville Center for Clinical Research ( Site 1014)	Jacksonville	Florida
United States	Wake Research Clinical Research Center of Nevada, LLC ( Site 1044)	Las Vegas	Nevada
United States	Unity Clinical Research ( Site 1036)	Lindsay	Oklahoma
United States	Community Clinical Research Network (Marlboro, MA) ( Site 1025)	Marlborough	Massachusetts
United States	Synexus ( Site 1043)	Mesa	Arizona
United States	Benchmark Research ( Site 1040)	Metairie	Louisiana
United States	Alpha Science Research ( Site 1015)	Miami	Florida
United States	L&C Professional Medical Research Institute ( Site 1012)	Miami	Florida
United States	Coastal Carolina Research Center ( Site 1034)	Mount Pleasant	South Carolina
United States	Synexus ( Site 1000)	Murray	Utah
United States	Valley Clinical Trials Inc. ( Site 1003)	Northridge	California
United States	Center for Clinical Trials, LLC ( Site 1019)	Paramount	California
United States	Rochester Clinical Research, Inc. ( Site 1039)	Rochester	New York
United States	Diagnostics Research Group ( Site 1042)	San Antonio	Texas
United States	California Research Foundation ( Site 1006)	San Diego	California
United States	Artemis Institute for Clinical Research ( Site 1041)	San Marcos	California
United States	Southwest CARE Center ( Site 1011)	Santa Fe	New Mexico
United States	Alta California Medical Group ( Site 1020)	Simi Valley	California
United States	QPS Miami Research Associates ( Site 1035)	South Miami	Florida
United States	Allegiance Research Specialists ( Site 1013)	Wauwatosa	Wisconsin
United States	Advanced Clinical Research ( Site 1028)	West Jordan	Utah
United States	PMG Research of Winston Salem ( Site 1037)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Australia,  Chile,  Denmark,  Finland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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