Cytomegalovirus Infection
Conditions
Keywords
Moderna, mRNA-1647, Cytomegalovirus, CMV, Cytomegalovirus Vaccine, Cytomegalovirus Infections, Cytomegalovirus Congenital, Virus Diseases, Infection Viral, DNA Virus Infections, Messenger RNA
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALmRNA-1647
Lyophilized product that is reconstituted with saline then diluted with a special diluent to reach the desired concentration
OTHERPlacebo
0.9% sodium chloride (normal saline) injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Observer-Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female 18-40 years of age (Part 1); Female 18-40 years of age (Part 2) * Understands and agrees to comply with the trial procedures and provides written informed consent * According to the assessment of the Investigator, is in good general health and is capable of complying with trial procedures * Body mass index (BMI) 18-35 kilograms/meter (kg/m\^2) * Female participants must either be of non-childbearing potential or use acceptable methods of contraception from at least 28 days prior to the first vaccination and through 3 months following last vaccination and is not breastfeeding. * Male participants must agree to practice adequate contraception from the time of the first vaccination and through 3 months after the last vaccination.
Exclusion criteria
* Acutely ill or febrile on the day of the first vaccination * Prior receipt of any CMV vaccine * Abnormal screening safety laboratory test results * Diagnosis or condition that, in the judgment of Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to trial procedures * Has received or plans to receive a vaccine ≤28 days prior to the first vaccination or plans to receive a non-study vaccine within 28 days prior to or after any study vaccination, except for any licensed influenza vaccine which can be administered \>14 days before or after any study vaccination. COVID-19 vaccines (regardless of manufacturer) may be administered \>7 days but preferably \>14 days before or after any study vaccination, with the intention of prioritizing COVID-19 vaccination over all other considerations. * Prior receipt of chronic systemic immunosuppressants or immune-modifying drugs * Receipt of intravenous immunoglobulins or plasma products within 3 months prior to the day of the first study vaccination * Previous receipt of medications in lipid nanoparticle (LNP) formulation (Part 1 participants only) * Has donated ≥450 milliliters (mL) of blood products within 28 days of the Screening visit * Participated in an interventional clinical trial within 28 days prior to the day of enrollment * Is an immediate family member or household member of trial personnel
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Up to Day 175 (7 days following last dose administration) | 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. |
| Number of Participants With Unsolicited Adverse Events (AEs) | Up to Day 196 (28 days following last dose administration) | 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." |
| Number of Participants With Medically Attended Adverse Events (MAAEs) | Up to Day 336 (6 months following last dose administration) | 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." |
| Number of Participants With Serious Adverse Events (SAEs) | Up to Day 504 (1 year following last dose administration) | 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." |
| Geometric Mean Titer (GMT) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection | Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| Geometric Mean Ratio (GMR) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| 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 | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| GMR of Anti-gB-specific IgG and Anti-Pentamer-specific IgG as Measured by ELISA of Post-Baseline/Baseline Titers | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| 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 | Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| 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 | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| 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 | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| GMT of Antigen-Specific IgG (ELISA) at Each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups | Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
| GMR of Antigen-Specific IgG (ELISA) at Each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups | Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 | 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. |
Countries
United States
Participant flow
Recruitment details
mRNA-1647-P202 was a 2-part study. For Part 1, participants were randomized to receive 1 of 3 dose levels (50, 100, 150 micrograms \[ug\]) of the mRNA-1647 vaccine and placebo in CMV-seronegative and CMV-seropositive male and female participants. For Part 2, new female participants (that is, did not participate in Part 1) who were either CMV-seronegative or CMV-seropositive were randomized to receive either the mRNA-1647 vaccine (100 ug) or placebo.
Pre-assignment details
Data were collected based on participant serostatus and the treatment group to which the participant was randomized regardless of the part of the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.1 years STANDARD_DEVIATION 6.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 265 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 72 | 0 / 45 | 0 / 53 | 0 / 18 | 0 / 37 | 0 / 18 | 0 / 27 |
| other Total, other adverse events | 40 / 45 | 67 / 72 | 44 / 45 | 38 / 53 | 18 / 18 | 36 / 37 | 18 / 18 | 20 / 27 |
| serious Total, serious adverse events | 0 / 45 | 1 / 72 | 0 / 45 | 0 / 53 | 0 / 18 | 1 / 37 | 0 / 18 | 0 / 27 |
Outcome results
None listed