This clinical study will assess the safety and immunogenicity of 3 dose levels of mRNA-1647 cytomegalovirus vaccine in CMV-seronegative and CMV-seropositive healthy adults 18-40 years of age.
mRNA-1647-P202 is a 2-part study. Part 1 of the study evaluates the safety and immunogenicity of 3 dose levels of mRNA-1647 vaccine or placebo, administered on a 0, 2, 6-month schedule in healthy CMV-seronegative and CMV-seropositive males and females, 18 to 40 years of age. A planned interim analysis of safety and immunogenicity through Month 3 (1 month after the second dose) of Part 1 of the study informed the selection of the middle dose level for further development. Part 2 of the study is designed to further evaluate the safety and immunogenicity of the middle dose level of mRNA-1647 vaccine or placebo on a 0, 2, 6-month schedule in approximately 200 healthy participants 18 to 40 years of age, comprised of CMV-seronegative and CMV-seropositive female population, which includes the target population for the pivotal Phase 3 efficacy trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
315
Benchmark Research
Sacramento, California, United States
Optimal Research
Peoria, Illinois, United States
Johnson County Clin-Trials
Lenexa, Kansas, United States
Alliance for Multispecialty Research
Lexington, Kentucky, United States
Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)
Solicited ARs were selected signs and symptoms occurring after vaccination administration during a specified post-vaccination follow-up period. The occurrence and intensity of the selected signs and symptoms was actively solicited from the participant during a specified post-vaccination follow-up period (day of vaccination and 6 subsequent days), using a predefined checklist in the electronic diary. The following local ARs were solicited: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the vaccination arm. The following systemic ARs were solicited: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, fever, and chills. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to Day 175 (7 days following last dose administration)
Number of Participants With Unsolicited Adverse Events (AEs)
An unsolicited AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. The treatment-emergent AEs are defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."
Time frame: Up to Day 196 (28 days following last dose administration)
Number of Participants With Medically Attended Adverse Events (MAAEs)
An MAAE is an AE that lead to a visit to a healthcare practitioner (HCP). This would include visits to study clinic for unscheduled assessments (for example, rash assessment, abnormal laboratory follow-up), and visits to HCPs external to the clinical site (for example, urgent care, primary care physician). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."
Time frame: Up to Day 336 (6 months following last dose administration)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Aventiv Research Inc
Columbus, Ohio, United States
Tekton Research Inc
Austin, Texas, United States
Crossroads Clinical Research
Victoria, Texas, United States
Foothill Family Clinic
Salt Lake City, Utah, United States
Foothill Family Clinic-South Clinic
Salt Lake City, Utah, United States
Number of Participants With Serious Adverse Events (SAEs)
An SAE was defined as any untoward medical occurrence that, in the view of either the Investigator or the Sponsor, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization or prolongation of hospitalization in the absence of a precipitating event was not in itself an SAE), resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."
Time frame: Up to Day 504 (1 year following last dose administration)
Geometric Mean Titer (GMT) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection
Blood samples for antibody-mediated immunogenicity (AMI) analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. Results are reported as fold dilution (titer). GMT 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Geometric Mean Ratio (GMR) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection
Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. The GMR measures the changes in immunogenicity titers within participants. Results are reported as a ratio (post-baseline/baseline titers). GMR 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Percentage of Participants With ≥2-Fold, 3-Fold, and 4-Fold Increases in Neutralizing Antibodies (nAb) Over Baseline Against Epithelial Cell Infection and Against Fibroblast Infection
Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV nAb titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. A ≥z-fold increase from baseline at participant level was defined as a ≥z \* the lower limit of quantification (LLOQ) for participants with baseline antibody level below the LLOQ, or a z-times or higher-level ratio in participants with baseline antibody level equal to or above the LLOQ. LLOQ=16. Results are reported as percentage of participants with ≥2-fold, 3-fold, and 4-fold increases in serum anti-CMV nAb titers from baseline. 95% CI for percentage is calculated using the Clopper-Pearson method.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMT of Anti-Glycoprotein B (gB)-Specific Immunoglobulin G (IgG) and Anti-Pentamer-specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) of Post-Baseline/Baseline Titers
Blood samples for antibody-mediated immunogenicity were collected during protocol-specified study visits. Serological assessment for anti-gB-specific IgG and anti-pentameric gH/gL/UL128/UL130/UL131A glycoprotein complex (Pentamer)-specific IgG binding was measured with ELISA. The GMT measures the level of inhibition of anti-gB-specific IgG (anti-gB) and anti-Pentamer-specific IgG (anti-Pentamer) against cytomegalovirus. Results are reported as fold dilution (titer). GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMR of Anti-gB-specific IgG and Anti-Pentamer-specific IgG as Measured by ELISA of Post-Baseline/Baseline Titers
Blood samples for antibody-mediated immunogenicity were collected during protocol-specified study visits. Serological assessment for anti-gB-specific IgG and anti-Pentamer-specific IgG binding was measured with ELISA. The GMR measures the changes in immunogenicity titers within participants. Results are reported as a ratio (post-baseline/baseline titers). GMR 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation. Number Analyzed = participants who were evaluable at specified timepoints.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMT of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group
Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV nAb titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. Results are reported as fold dilution (titer). GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMR of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group
Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV nAb titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. The GMR measures the changes in immunogenicity titers within participants. Results are reported as a ratio (post-baseline/baseline titers). GMR 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Percentage of Participants With ≥2-Fold, 3-Fold, and 4-Fold Increases Over Baseline of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection in the CMV-Seropositive and CMV-Seronegative Groups
Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV nAb titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. A ≥z-fold increase from baseline at participant level was defined as a ≥z \* the LLOQ for participants with baseline antibody level below the LLOQ, or a z-times or higher-level ratio in participants with baseline antibody level equal to or above the LLOQ. LLOQ=16. Results are reported as percentage of participants with ≥2-fold, 3-fold, and 4-fold increases in serum anti-CMV nAb titers from baseline. 95% CI for percentage is calculated using the Clopper-Pearson method.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMT of Antigen-Specific IgG (ELISA) at Each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups
Blood samples for antibody-mediated immunogenicity were collected during protocol-specified study visits. Serological assessment for anti-gB-specific IgG and anti-Pentamer-specific IgG binding was measured with ELISA. Results are reported as fold dilution (titer). GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
GMR of Antigen-Specific IgG (ELISA) at Each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups
Blood samples for antibody-mediated immunogenicity were collected during protocol-specified study visits. Serological assessment for anti-gB-specific IgG and anti-Pentamer-specific IgG binding was measured with ELISA. The GMR measures the changes in immunogenicity titers within participants. Results are reported as a ratio (post-baseline/baseline titers). GMR 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504