Safety, Tolerability, and Immunogenicity of V110 or V114 Co-administered With a Booster Dose of mRNA-1273 in Healthy Adults (V110-911)

Pneumococcal Infection Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Concomitant Administration of Either 23-Valent Pneumococcal Polysaccharide Vaccine or 15-Valent Pneumococcal Conjugate Vaccine With a Booster Dose of SARS-CoV-2 mRNA Vaccine in Healthy Adults 50 Years of Age or Older.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05158140
• Other study ID #: V110-911
• Status: Completed
• Phase: Phase 3
• Start date: January 12, 2022
• Est. completion date: February 21, 2023

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the concomitant and non-concomitant use of messenger ribonucleic acid (mRNA) mRNA-1273, the nucleoside-modified mRNA vaccine for active immunization to prevent coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), with a 23-valent pneumococcal polysaccharide vaccine (V110) for the prevention of pneumococcal disease, or a 15-valent pneumococcal conjugate vaccine (V114) indicated for the prevention of invasive pneumococcal disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: February 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Is in good health

• Any underlying chronic illness must be documented to be in stable condition

• Has received a 2-dose primary series of the Moderna mRNA SARS-CoV-2 vaccine =5 months before receipt of study vaccine at Visit 1

• May have received either: a) A first booster dose of the Moderna mRNA SARS-CoV-2 vaccine =4 months before receipt of study vaccine at Visit 1, or b) No booster dose of the Moderna mRNA SARS-CoV-2 vaccine

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using an acceptable contraceptive method, or is abstinent from heterosexual intercourse

Exclusion Criteria:

• Has a current SARS-CoV-2 infection or a known history of SARS-CoV-2 infection <3 months before receipt of study vaccine at Visit 1

• Has a history of myocarditis and/or pericarditis

• Has a 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

• Has a coagulation disorder contraindicating intramuscular vaccinations

• Had a recent illness with fever (defined as oral or tympanic temperature =100.4°F [=38.0°C]; axillary or temporal temperature =99.4°F [=37.4°C]) or received antibiotic therapy for an acute illness occurring <72 hours before receipt of study vaccine

• Has a known malignancy that is progressing or has required active treatment <3 years before receipt of study vaccine at Visit 1

• Received prior administration of a pneumococcal polysaccharide vaccine <5 years before study enrollment or is expected to receive a pneumococcal polysaccharide vaccine during the study outside the protocol

• Received prior administration of a PCV <1 year before receipt of study vaccine at Visit 1 or is expected to receive a PCV during the study outside the protocol

• Received prior administration of any SARS-CoV-2 vaccine other than the 2-dose primary series of the Moderna mRNA vaccine with or without a first booster dose, or is expected to receive any SARS-CoV-2 vaccine during the study outside the protocol

• Received prior monoclonal antibody treatment for SARS-CoV-2 infection

• Received antiviral treatment for SARS-CoV-2 infection <3 months before receipt of study vaccine at Visit 1

• Received systemic corticosteroids for =14 consecutive days and has not completed intervention =30 days before receipt of study vaccine at Visit 1

• Received systemic corticosteroids exceeding physiologic replacement doses =14 days before receipt of study vaccine

• Is currently 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

• Received any non-live vaccine =14 days before receipt of study vaccine or is scheduled to receive any non-live vaccine =30 days after receipt of study vaccine. Exception: Inactivated influenza vaccine allowed if given =7 days before or =15 days after receipt of study vaccine

• Received any live virus vaccine =30 days before receipt of study vaccine or is scheduled to receive any live virus vaccine =30 days after receipt of study vaccine

• Received a blood transfusion or blood products (including globulin) =6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product =30 days after receipt of study vaccine

• Is 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

Related Conditions & MeSH terms

• Pneumococcal Infection
• Pneumococcal Infections

Intervention

Biological:
• V110
Single intramuscular (IM) dose of 0.5 mL V110, a pneumococcal polysaccharide vaccine (PCV), containing the 23 serotypes: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F
• V114
Single IM dose of 0.5 mL V114 a 15-valent PCV containing the 15 serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F
• mRNA-1273
Single IM dose of 50 µg/0.25 mL mRNA-1273
• Placebo for V110
Single IM dose of 0.5 mL placebo for V110
• Placebo for V114
Single IM dose of 0.5 mL placebo for V114

Locations

Country	Name	City	State
Puerto Rico	Cooperativa de Facultad Medica SANACOOP ( Site 0104)	Bayamon
Puerto Rico	CAIMED Center - Ponce School of Medicine ( Site 0103)	Ponce
Puerto Rico	Caparra Internal Medicine Research Center. PSC ( Site 0102)	Rio Grande
Puerto Rico	Clinical Research Puerto Rico ( Site 0105)	San Juan
United States	Atlanta Center For Medical Research ( Site 0053)	Atlanta	Georgia
United States	Benchmark Research ( Site 0007)	Austin	Texas
United States	Charlottesville Medical Research Center, LLC ( Site 0008)	Charlottesville	Virginia
United States	Velocity Clinical Research- Cleveland ( Site 0023)	Cleveland	Ohio
United States	Alliance for Multispecialty Research, LLC ( Site 0036)	Coral Gables	Florida
United States	South Texas Clinical Research ( Site 0033)	Corpus Christi	Texas
United States	Certified Research Associates ( Site 0042)	Cortland	New York
United States	Velocity Clinical Research-Providence ( Site 0015)	East Greenwich	Rhode Island
United States	Centennial Medical Group ( Site 0016)	Elkridge	Maryland
United States	Benchmark Research ( Site 0039)	Fort Worth	Texas
United States	University of Texas Medical Branch at Galveston ( Site 0037)	Galveston	Texas
United States	Indago Research and Health Center Inc ( Site 0006)	Hialeah	Florida
United States	Corning Center for Clinical Research ( Site 0052)	Horseheads	New York
United States	Texas Center For Drug Development ( Site 0013)	Houston	Texas
United States	Alliance for Multispecialty Research, LLC ( Site 0011)	Kansas City	Missouri
United States	Wake Research Clinical Research Center of Nevada, LLC ( Site 0021)	Las Vegas	Nevada
United States	AMR Lexington ( Site 0055)	Lexington	Kentucky
United States	Community Clinical Research Center ( Site 0032)	Marlborough	Massachusetts
United States	Wellness Clinical Research Associates ( Site 0051)	McKinney	Texas
United States	Optimal Research LLC ( Site 0019)	Melbourne	Florida
United States	Advanced Medical Research, LLC ( Site 0030)	Miami	Florida
United States	Lakes Research LLC ( Site 0012)	Miami Lakes	Florida
United States	Health Research of Hampton Roads, Inc. ( Site 0014)	Newport News	Virginia
United States	Alliance for Multispecialty Research, LLC ( Site 0018)	Newton	Kansas
United States	Alliance for Multispecialty Research LLC (AMR - Norfolk) ( Site 0057)	Norfolk	Virginia
United States	Coastal Carolina Research Center ( Site 0044)	North Charleston	South Carolina
United States	Carbon Health ( Site 0045)	North Hollywood	California
United States	Valley Clinical Trials Inc. ( Site 0002)	Northridge	California
United States	Center for Clinical Trials, LLC ( Site 0022)	Paramount	California
United States	Optimal Research ( Site 0054)	Peoria	Illinois
United States	Clinical Research Partners, LLC. ( Site 0005)	Richmond	Virginia
United States	Rochester Clinical Research, Inc. ( Site 0010)	Rochester	New York
United States	Diagnostics Research Group ( Site 0001)	San Antonio	Texas
United States	Artemis Institute for Clinical Research ( Site 0024)	San Diego	California
United States	California Research Foundation ( Site 0004)	San Diego	California
United States	AXCES Research Group ( Site 0017)	Santa Fe	New Mexico
United States	Millennium Clinical Trials ( Site 0027)	Simi Valley	California
United States	DM Clinical Research ( Site 0025)	Tomball	Texas
United States	Crossroads Clinical Research LLC ( Site 0020)	Victoria	Texas
United States	Diablo Clinical Research, Inc ( Site 0043)	Walnut Creek	California
United States	Velocity Clinical Research, Salt Lake City ( Site 0035)	West Jordan	Utah
United States	Accellacare - Winston-Salem ( Site 0049)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Solicited Injection-Site Adverse Events (AEs) Among Participants Administered V110	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 include redness, swelling, pain/tenderness, and underarm gland swelling or tenderness/lymphadenopathy at the injection site. The percentage of participants with one or more solicited injection-site AEs following any vaccination was reported.	Up to Day 7 After Any Vaccination (Up to Study Day 37)
Primary	Percentage of Participants With Solicited Injection-Site Adverse Events Among Participants Administered V114	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 injection-site AEs include redness, swelling, pain/tenderness, and underarm gland swelling or tenderness/lymphadenopathy at the injection site. The percentage of participants with one or more solicited injection-site AEs following any vaccination was reported.	Up to Day 7 After Any Vaccination (Up to Study Day 37)
Primary	Percentage of Participants With Solicited Systemic AEs Among Participants Administered V110	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Systemic adverse events (AEs) include headache, tiredness/fatigue, muscle aches all over body/myalgia, joint pain/arthralgia, nausea, vomiting, and chills. The percentage of participants with solicited systemic AEs following any vaccination was reported.	Up to Day 7 After Any Vaccination (Up to Study Day 37)
Primary	Percentage of Participants With Solicited Systemic AEs Among Participants Administered V114	An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Systemic adverse events (AEs) include headache, tiredness/fatigue, muscle aches all over body/myalgia, joint pain/arthralgia, nausea, vomiting, and chills. The percentage of participants with solicited systemic AEs following any vaccination was reported.	Up to Day 7 After Any Vaccination (Up to Study Day 37)
Primary	Percentage of Participants With Vaccine-Related Serious AEs (SAEs) Among Participants Administered V110	Serious adverse events (SAEs) are defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in offspring of a participant, or other important medical events. V110 vaccine-related SAEs as determined by investigator are summarized.	Up to Month 6
Primary	Percentage of Participants With Vaccine-Related SAEs Among Participants Administered V114	SAEs are defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in offspring of a participant, or other important medical events. V114 vaccine-related SAEs as determined by investigator are summarized.	Up to Month 6
Primary	Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) in Participants Administered V110	Serotype-specific OPA GMTs for 14 of the serotypes contained in V110 were determined using a multiplexed opsonophagocytic assay (MOPA) at 30 days postvaccination with V110. The within-group 95% confidence intervals (CIs) were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	Up to 30 days postvaccination with V110 (Study Day 30 for concomitant vaccination group, and Study Day 60 for nonconcomitant vaccination group, respectively)
Primary	Serotype-specific OPA GMT in Participants Administered V114	Serotype-specific OPA GMTs for 15 of the serotypes contained in V114 were determined using a MOPA at 30 days postvaccination with V114. The within-group 95% CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	Up to 30 days postvaccination with V114 (Study Day 30 for concomitant vaccination group, and Study Day 60 for nonconcomitant vaccination group, respectively)
Primary	SARS-CoV-2-specific Binding Antibody (bAb) GMT in Participants Administered Either V110 or V114	Sera from participants were used to measure vaccine-induced bAb responses using a validated ligand-binding assay specific to the SARS-CoV-2 Spike protein at 30 days post vaccination. The within-group 95% CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution. As prespecified by the protocol and statistical analysis plan, the V110 nonconcomitant group and V114 nonconcomitant group were combined for this analysis, as they shared the same administration for the first visit (mRNA-1273 and placebo).	Up to 30 days postvaccination with mRNA-1273 (Study Day 30)
Secondary	Serotype-specific OPA Geometric Mean Fold Rise (GMFR) in Participants Administered V110	Serotype-specific OPA for 14 of the serotypes contained in V110 was determined using a MOPA. GMFR is the geometric mean fold rise from baseline to 30 days postvaccination. The within-group 95% confidence intervals (CIs) were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	Baseline and 30 days postvaccination with V110 (Study Day 1 and Study Day 30 for concomitant vaccination group, and Study Day 30 and Study Day 60 for nonconcomitant vaccination group, respectively)
Secondary	Serotype-specific OPA GMFR in Participants Administered V114	Serotype-specific OPA for all 15 of the serotypes contained in V114 were determined using a MOPA. GMFR is the geometric mean fold rise from baseline to 30 days postvaccination. The within-group 95% CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.	Baseline and 30 days postvaccination with V114 (Study Day 1 and Study Day 30 for concomitant vaccination group, and Study Day 30 and Study Day 60 for nonconcomitant vaccination group, respectively)
Secondary	SARS-CoV-2-specific Binding Antibody (bAb) GMFR in Participants Administered Either V110 or V114	Sera from participants was used to measure vaccine-induced bAb responses using a validated ligand-binding assay specific to the SARS-CoV-2 Spike protein. GMFR is the geometric mean fold rise from baseline to 30 days postvaccination. The within-group 95% CIs were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution. As prespecified by the protocol and statistical analysis plan, the V110 nonconcomitant group and V114 nonconcomitant group were combined for this analysis, as they shared the same administration for the first visit (mRNA-1273 and placebo).	Baseline and 30 days postvaccination with mRNA-1273 (Study Day 1 and Study Day 30, respectively)
Secondary	Percentage of Participants Who Achieve a =4-fold Rise in Serotype-specific OPA Responses From Baseline to 30 Days Postvaccination With V110	Serotype-specific OPA for 14 of the serotypes contained in V110 was determined using a MOPA. The percentage of participants who achieved a =4-fold rise in OPA titer from baseline to 30 days postvaccination were calculated. The within-group 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.	Baseline and 30 days postvaccination with V110 (Study Day 1 and Study Day 30 for concomitant vaccination group, and Study Day 30 and Study Day 60 for nonconcomitant vaccination group, respectively)
Secondary	Percentage of Participants Who Achieve a =4-fold Rise in Serotype-specific OPA Responses From Baseline to 30 Days Postvaccination With V114	Serotype-specific OPA for all 15 of the serotypes in V114 were determined using a MOPA. The percentage of participants who achieved a =4-fold rise in OPA titer from baseline to 30 days postvaccination were calculated. The within-group 95% CIs are based on the exact binomial method proposed by Clopper and Pearson.	Baseline and 30 days postvaccination with V114 (Study Day 1 and Study Day 30 for concomitant vaccination group, and Study Day 30 and Study Day 60 for nonconcomitant vaccination group, respectively)
Secondary	Percentage of Participants With =4 Fold Rise From Baseline in SARS-CoV-2-specific bAb Response	Sera from participants was used to measure vaccine-induced bAb responses using a validated ligand-binding assay specific to the SARS-CoV-2 Spike protein. The percentage of participants who achieved a =4-fold rise in bAb titer from baseline to 30 days postvaccination were calculated. The within-group 95% CIs are based on the exact binomial method proposed by Clopper and Pearson. As prespecified by the protocol and statistical analysis plan, the V110 nonconcomitant group and V114 nonconcomitant group were combined for this analysis, as they shared the same administration for the first visit (mRNA-1273 and placebo).	Baseline and 30 days postvaccination with mRNA-1273 (Study Day 1 and Study Day 30, respectively)

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary