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

Merck Sharp & Dohme LLC850 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

850

Conditions

Pneumococcal Infection

Interventions

V110

Eligibility

Sex: ALLMin age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (46)

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

Artemis Institute for Clinical Research ( Site 0024)

San Diego, California, United States

California Research Foundation ( Site 0004)

San Diego, California, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to Day 7 After Any Vaccination (Up to Study Day 37)

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.

Time frame: Up to Day 7 After Any Vaccination (Up to Study Day 37)

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.

Time frame: Up to Day 7 After Any Vaccination (Up to Study Day 37)

Percentage of Participants With Solicited Systemic AEs Among Participants Administered V114

Time frame: Up to Day 7 After Any Vaccination (Up to Study Day 37)

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.

Time frame: Up to Month 6

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.

Time frame: Up to Month 6

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.

Time frame: Up to 30 days postvaccination with V110 (Study Day 30 for concomitant vaccination group, and Study Day 60 for nonconcomitant vaccination group, respectively)

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.

Time frame: Up to 30 days postvaccination with V114 (Study Day 30 for concomitant vaccination group, and Study Day 60 for nonconcomitant vaccination group, respectively)

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).

Time frame: Up to 30 days postvaccination with mRNA-1273 (Study Day 30)

Secondary Outcomes

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.

Time frame: 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)

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.

Time frame: 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)

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).

Time frame: Baseline and 30 days postvaccination with mRNA-1273 (Study Day 1 and Study Day 30, respectively)

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.

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.

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).

Time frame: Baseline and 30 days postvaccination with mRNA-1273 (Study Day 1 and Study Day 30, respectively)