Respiratory Syncytial Virus
Conditions
Keywords
Pediatric, mRNA-1345, RSV vaccine, Viral Diseases, Messenger RNA, Moderna
Brief summary
Part A: The purpose is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1345 in children aged 2 to \<5 years (Cohort 1) and in children at high risk of respiratory syncytial virus (RSV) disease 5 to \<18 years of age (Cohort 2) to inform the dose level selection for the next phase of development (Phase 3). Part B: The purpose is to provide surveillance for RSV disease for the next RSV season (6 months after re-enrollment) and safety follow-up for Cohort 1 participants that were enrolled and dosed in Part A.
Interventions
BIOLOGICALmRNA-1345
Sterile liquid for injection
BIOLOGICALPlacebo
0.9% sodium chloride (normal saline) injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: Part A Cohort 1: * 2 to \<5 years of age at Day 1. * Healthy, or with stable chronic conditions increasing the risk of RSV disease, per the clinical judgment of the Investigator. Cohort 2: * 5 to \<18 years of age at Day 1. * Participants with stable chronic conditions increasing the risk of RSV disease. * Female participants of child-bearing potential may be enrolled in the study, if the participant: 1) has a negative urine pregnancy test at Screening and on the day of injection (Day 1); 2) has practiced adequate contraception or has abstained from all activities that could lead to pregnancy for 28 days prior to Day 1; 3) has agreed to continue adequate contraception through 90 days following injection; and 4) is not currently breastfeeding. Part B: Cohort 1 Re-enrollment Participants are eligible to be included in the study only if all of the following criteria apply: 1. Enrolled and dosed in Part A of Cohort 1; either reached EoS for Part A or were dosed and subsequently discontinued from study for various reasons. This includes participants who were lost to follow-up, if they can be re-engaged. 2. Participant's parent(s)/LAR(s) has provided written informed consent for participation in this study. Key
Exclusion criteria
(All Cohorts): * Acutely ill or febrile (temperature ≥38.0°Celsius \[100.4°Fahrenheit\]) within 72 hours prior to or at the Screening Visit or Day 1. * History of a diagnosis or condition that, in the judgment of the Investigator, may affect study assessment or compromise participant safety. * Has received or plans to receive any licensed or authorized vaccine ≤14 days prior to the study vaccine injection (Day 1) or plans to receive a licensed or authorized vaccine within 14 days after the study vaccine injection. * Receipt of any prior systemic immunosuppressants. Short courses (\<7 days) of oral corticosteroids are allowed if completed at least 3 months prior to enrollment. * Receipt of RSV monoclonal antibodies within 6 months prior to enrollment in the study. * Participated in an interventional clinical study within 28 days (6 months for a study assessing a product unlicensed/unauthorized in this age group in country of residence at time of enrollment) prior to the day of enrollment or plans to do so while enrolled in this study. Part B: Cohort 1 Re-enrollment 1\. Participant is currently enrolled in another interventional clinical study. Note: Other protocol-defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A (Cohorts 1 and 2): Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) | Up to 7 days post-injection | Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). Investigator reviewed whether the solicited AR was also to be recorded as an AE. A summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
| Part A (Cohorts 1 and 2): Number of Participants With Unsolicited Adverse Events (AEs) | Up to 28 days post-injection | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
| Part A (Cohorts 1 and 2): Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation | Day 1 through end of Part A (Month 6) | A MAAE was an AE that led to an unscheduled visit to a healthcare practitioner. An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
| Part B (Cohort 1): Number of Participants With RSV-RTD, Respiratory Syncytial Virus- Lower Respiratory Tract Disease (RSV-LRTD), Severe RSV-LRTD, Very Severe RSV-LRTD and RSV Hospitalization Classified by Clinical Assessment Team (CAT) | Day 1 through end of Part B (Month 6) | RSV-RTD: Runny nose or blocked nose or cough and confirmed RSV infection. RSV-LRTD: Cough or difficulty breathing (Based on Investigator's observation; difficulty breathing included signs of wheezing, stridor, tachypnoea, chest in-drawing or subcostal or intercostal retractions) and peripheral oxygen saturation (SpO2) \<95%, or respiratory rate (RR) increased and confirmed RSV infection. RSV Severe-LRTD: Meeting the definition of RSV-LRTD and SpO2 \<93%, or lower chest wall in-drawing. RSV Very Severe LRTD: Meeting the definition of RSV-LRTD and SpO2 \<90%, or failure to respond/unconscious. RSV Hospitalization: Confirmed RSV and hospitalized for acute medical condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A (Cohort 1): Geometric Mean Titer (GMT) of Serum RSV Neutralizing Antibody | Day 1, Day 29, and Month 6 | Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 international units (IU)/milliliter (mL) for RSV-A and 10 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 112476 IU/mL for RSV-B. 95% confidence interval (CI) for geometric mean (GM) value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. |
| Part A (Cohort 1): Geometric Mean Concentration (GMC) of Serum RSV Prefusion F (Pre-F) Binding Antibody | Day 1, Day 29, and Month 6 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 arbitrary units (AU)/mL and ULOQ was 580553 AU/mL for RSV Pre-F immunoglobulin G (IgG) antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. |
| Part A (Cohort 1): Geometric Mean Fold Rise (GMFR) of Post-baseline/Baseline Neutralizing Antibody Titers | Day 29 and Month 6 | Antibody values reported as below lower LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 10 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 112476 IU/mL for RSV-B. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. |
| Part A (Cohort 1): GMFR of Post-baseline/Baseline Binding Antibody Concentrations | Day 29 and Month 6 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 AU/mL and ULOQ was 580553 AU/mL for RSV Pre-F IgG antibody. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. |
| Part A (Cohort 1): Percentage of Participants With Seroresponse in RSV Neutralizing Antibody | Baseline to Day 29 and Month 6 | Seroresponse was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. |
| Part A (Cohort 1): Percentage of Participants With Seroresponse in RSV Pre-F Binding Antibody | Baseline to Day 29 and Month 6 | Seroresponse was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. |
| Part A (Cohort 2): GMT of Serum RSV Neutralizing Antibody | Day 1 and Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 15 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 162163 IU/mL for RSV-B. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. |
| Part A (Cohort 2): GMC of Serum RSV Pre-F Binding Antibody | Day 1 and Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 AU/mL and ULOQ was 580553 AU/mL for RSV Pre-F IgG antibody. 95% CI for GM value was calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. |
| Part A (Cohort 2): GMFR of Post-baseline/Baseline Neutralizing Antibody Titers | Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 13 IU/mL for RSV-A and 15 IU/mL for RSV-B. ULOQ was 259061 IU/mL for RSV-A and 162163 IU/mL for RSV-B. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. |
| Part A (Cohort 2): GMFR of Post-baseline/Baseline Binding Antibody Concentrations | Day 29 | Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than ULOQ were replaced by the ULOQ. LLOQ was 35 AU/mL and ULOQ was 580553 AU/mL for RSV Pre-F IgG antibody. 95% CI for GMFR (post-injection/baseline titers) was calculated based on the t-distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation. |
| Part A (Cohort 2): Percentage of Participants With Seroresponse in RSV Neutralizing Antibody | Baseline to Day 29 | Seroresponse was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. |
| Part A (Cohort 2): Percentage of Participants With Seroresponse in RSV Pre-F Binding Antibody | Baseline to Day 29 | Seroresponse was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. |
| Part B (Cohort 1): Number of Participants With AESIs and SAEs | Day 1 through Part B EOS (Month 6) | An AESI was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section. |
Countries
Panama, United States
Participant flow
Pre-assignment details
This study consisted of 2 parts (Parts A and B). Part A consisted of 2 cohorts. For Part B, all Cohort 1 participants who were enrolled and dosed in Part A, were offered to re-enroll into the safety follow-up study. Participants who were in Part B were not administered any study drug.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants |
| Age, Customized Children (2-11 years) | 40 Participants |
| Age, Customized From 65-84 years | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 104 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 245 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 118 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 26 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 27 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 39 | 0 / 41 | 0 / 41 | 0 / 61 | 0 / 61 | 0 / 62 | 0 / 19 | 0 / 24 | 0 / 25 | 0 / 24 |
| other Total, other adverse events | 1 / 41 | 3 / 39 | 1 / 41 | 7 / 41 | 5 / 61 | 0 / 61 | 0 / 62 | 0 / 19 | 0 / 24 | 0 / 25 | 0 / 24 |
| serious Total, serious adverse events | 0 / 41 | 0 / 39 | 0 / 41 | 0 / 41 | 0 / 61 | 0 / 61 | 3 / 62 | 0 / 19 | 0 / 24 | 1 / 25 | 0 / 24 |
Outcome results
None listed