Respiratory Syncytial Virus
Conditions
Keywords
Viral Diseases, Messenger RNA, Moderna, mRNA-1345, Respiratory syncytial virus, Safety, Vaccines
Brief summary
The main purpose of Part A of this study is to evaluate the safety and tolerability of mRNA-1345 vaccine and to demonstrate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV-associated lower respiratory tract disease (RSV-LRTD) as compared with placebo from 14 days postinjection through 12 months. The main purpose of Part B of this study is to evaluate the safety, tolerability and immunogenicity of a booster dose (BD) of mRNA-1345 administered 24 months after the primary dose.
Detailed description
The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Part A Phase 2 segment, up to 2,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio. In the Part A Phase 3 segment, approximately 35,000 participants will be randomly assigned to receive a single injection of either mRNA-1345 vaccine at the selected dose or placebo in a 1:1 randomization ratio. In the Part B substudy, 1500 participants who received a dose of mRNA-1345 in Part A Phase 3 will be randomly assigned in a 2:1 randomization ratio to receive a single BD injection of either mRNA-1345 at the selected dose or placebo.
Interventions
DRUGPlacebo
0.9% sodium chloride (normal saline) injection
DRUGmRNA-1345
Sterile liquid for 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
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria (Part A): * Adults ≥ 60 years of age who are primarily responsible for self-care and activities of daily living. Participants may have one or more chronic medical diagnoses (including chronic heart failure \[CHF\] and chronic obstructive pulmonary disease \[COPD\]), but should be medically stable * Body mass index from ≥18 kilograms (kg)/square meter (m\^2) to ≤35 kg/m\^2 Key Inclusion Criteria (Part B): * Randomized to and were subsequently vaccinated with the mRNA-1345 study injection in Part A at least 21 months prior to Screening. Key
Exclusion criteria
(Part A): * Participation in another clinical research study where participant has received an investigational product (drug/biologic/device) within 6 months before the planned date of the Day 1 study injection. * Current participation in research involving receipt of any investigational RSV product * History of a serious reaction to any prior vaccination or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization. * Received or plans to receive any non-study vaccine within 28 days before or after the Day 1 study injection. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With Any Solicited Adverse Reactions (ARs) (Solicited Local and/or Systemic ARs) | Up to 7 days postinjection | 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 B: Number of Participants With Solicited Local and Systemic ARs | Up to 7 days post-BD injection | Solicited ARs were recorded daily using electronic diaries (eDiaries). 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 all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part A: Number of Participants With Unsolicited Adverse Events (AEs) | Up to 28 days postinjection | An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part B: Number of Participants With Unsolicited AEs | Up to 28 days post-BD injection | An unsolicited AE was defined as any AE reported by the participant that was not specified as a solicited AR in the protocol. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part A: Number of Participants With Medically Attended AEs (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation | Up to 24 months postinjection | MAAEs were AEs that led to an unscheduled visit to a healthcare provider. AESIs were AEs (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 was required. SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part B: Number of Participants With MAAEs, AESIs, SAEs, and AEs Leading to Study Discontinuation | Up to BD Day 181 | MAAEs were AEs that led to an unscheduled visit to a healthcare provider. AESIs were AEs (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 was required. SAEs were AEs that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly or birth defect, or was a medically important event. A summary of all SAEs and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
| Part A: Number of Participants With Respiratory Syncytial Virus- Associated Lower RSV-LRTD With 2 or More Symptoms From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | RSV-LRTD: Reverse transcriptase polymerase chain reaction (RT PCR) confirmed RSV infection PLUS new or worsening of ≥2 of the following symptoms: shortness of breath, cough and/or fever (≥37.8 degrees Celsius \[°C\]), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥3 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part B: Geometric Mean Titer (GMT) of Serum Respiratory Syncytial Virus Subtype A (RSV-A) and Respiratory Syncytial Virus Subtype B (RSV-B) Neutralizing Antibodies (nAb) at BD Day 29 Compared to Primary Dose Day 29 | Primary Dose Day 29 and BD Day 29 | Antibody values reported as below lower limit of quantification (LLOQ) replaced by 0.5 \* LLOQ. Values greater than upper limit of quantification (ULOQ) replaced by ULOQ. LLOQ = 13 international units (IU)/milliliter (mL), ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part B Per-protocol (PP) Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With RSV-Associated Acute Respiratory Disease (RSV-ARD) From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | RSV-ARD: RT-PCR-confirmed RSV infection PLUS an acute symptomatic respiratory disease manifesting as new or worsening of 1 or more of cough, stuffy nose, runny nose, sore throat, fever (≥37.8°C), shortness of breath, observed tachypnea (≥20 breaths/minute or increase of ≥2 breaths/minute from baseline in those who have baseline tachypnea), hypoxemia (new oxygen saturation ≤ 93%, or new or increasing use of supplemental oxygen), wheezing, sputum production, hoarseness, sinus pain, chills, pleuritic chest pain for at least 24 hours. |
| Part A: Number of Participants With Hospitalization Associated With Protocol-defined RSV-ARD or RSV-LRTD From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | A case of first hospitalization associated with protocol-defined RSV-ARD or RSV-LRTD was defined if: (a) The investigator assessed that an event was a confirmed diagnosis of RSV-LRTD or RSV-ARD and that required inpatient or prolongation of existing hospitalization; (b) a protocol-defined RSV-LRTD/RSV-ARD occurred; (c) date of protocol-defined RSV-LRTD/RSV-ARD was within 14 days prior or during hospitalization. RSV-ARD defined in Outcome Measure #10 and RSV-LRTD defined in Outcome Measure #7 above. |
| Part A: Number of Participants With All-Cause Hospitalizations From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | An all-cause hospitalization was defined as any reported hospitalization which was collected as inpatient or prolongation of existing hospitalization in the electronic case report form (eCRF) AE form. |
| Part A: Number of Participants With All-Cause LRTD From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | All-cause LRTD: New or worsening of ≥2 of following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours with any or no RT-PCR result. All-cause LRTD was derived based on eligible LRTD symptoms onset within a respiratory illness episode. |
| Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms From 14 Days Postinjection up to 24 Months Postinjection | From 14 days postinjection up to 24 months postinjection | RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥3 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part A: Number of Participants With RSV-LRTD With 2 or More Symptoms From 14 Days Postinjection up to 24 Months Postinjection | From 14 days postinjection up to 24 months postinjection | RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥2 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part A: Number of Participants With RSV-LRTD With 2 or More Symptoms by RSV Subtype A and RSV Subtype B From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥2 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part A: Number of Participants With RSV-LRTD With 3 or More Symptoms by RSV Subtype A and RSV Subtype B From 14 Days Postinjection up to 12 Months Postinjection | From 14 days postinjection up to 12 months postinjection | RSV-LRTD: RT PCR confirmed RSV infection PLUS new or worsening of ≥3 of the following symptoms: shortness of breath, cough and/or fever (≥37.8°C), wheezing and/or rales and/or rhonchi, sputum production, tachypnea (≥20 breaths/minute or increase of ≥ 2 breaths/minute from baseline measurement in those who had baseline tachypnea), hypoxemia (new oxygen saturation ≤93% or new or increasing use of supplemental oxygen), pleuritic chest pain for ≥24 hours. |
| Part A: Number of Participants With First Hospitalization Associated With Protocol-defined RSV-ARD or RSV-LRTD From 14 Days Postinjection up to 24 Months Postinjection | From 14 days postinjection up to 24 months postinjection | A case of first hospitalization associated with protocol-defined RSV-ARD or RSV-LRTD was defined if: (a) The investigator assessed that an event was a confirmed diagnosis of RSV-LRTD or RSV-ARD and that required inpatient or prolongation of existing hospitalization; (b) a protocol-defined RSV-LRTD/RSV-ARD occurred; (c) date of protocol-defined RSV-LRTD/RSV-ARD was within 14 days prior or during hospitalization. RSV-ARD defined in Outcome Measure #10 and RSV-LRTD defined in Outcome Measure #7 above. |
| Part A: Change in Total Frailty Score From Baseline to 12 Months and 24 Months Postinjection, Using the Edmonton Frail Scale (EFS) | Baseline, 12 months and 24 months postinjection | The total frail score is the sum of individual scores from the 11 questions representing 9 domains included in EFS, which is a multidimensional frail assessment scale that assesses domains related to frailty including cognition, general health status, functional independence, social support, medication use, nutrition, mood, continence, and functional performance. The total frail score ranges between 0 and 17. Higher scores suggest more frailty, and the total frail score can be interpreted as: 0-3=fit, 4-5=vulnerable, 6-7=mild frail, 8-9=moderate frail, 10 or more=severe frail. |
| Part A: GMT of Serum RSV nAb | Baseline (Day 1), Days 29, 181, 365, and 730 | Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ replaced by ULOQ. LLOQ = 13 IU/mL, ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part A Per-protocol Immunogenicity (PPI) Set: a randomly selected subset of participants who: a) received the assigned study drug, b) had RSV immunogenicity titer results at baseline (prior to study drug administration) and at least 1 valid result after the study drug administration at timepoint of interest, and c) had no major protocol deviation affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. |
| Part A: Geometric Mean Concentration (GMC) of Serum RSV Binding Antibodies | Baseline (Day 1), Days 29, 181, 365, and 730 | Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ replaced by ULOQ. LLOQ = 35 arbitrary unit (AU)/mL, ULOQ = 580553 AU/mL for RSV Pre-F immunoglobulin G (IgG) antibody (Ab). LLOQ = 57, ULOQ = 847551 for RSV Post-F IgG Ab. Part A PPI Set: a randomly selected subset of participants who: a) received the assigned study drug, b) had RSV immunogenicity titer results at baseline (prior to study drug administration) and at least 1 valid result after the study drug administration at timepoint of interest, and c) had no major protocol deviation affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. |
| Part A: Percentage of Participants With Seroresponse in RSV nAb | Days 29, 181, 365, and 730 | 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 PPI Set: a randomly selected subset of participants who: a) received the assigned study drug, b) had RSV immunogenicity titer results at baseline (prior to study drug administration) and at least 1 valid result after the study drug administration at timepoint of interest, and c) had no major protocol deviation affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. |
| Part A: Geometric Mean Fold-Rise (GMFR) of Postbaseline/Baseline Antibody Titers | Days 29, 181, 365, and 730 | Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ replaced by ULOQ. LLOQ = 13 IU/mL, ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part A PPI Set: a randomly selected subset of participants who: a) received the assigned study drug, b) had RSV immunogenicity titer results at baseline (prior to study drug administration) and at least 1 valid result after the study drug administration at timepoint of interest, and c) had no major protocol deviation affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. |
| Part A: Percentage of Participants With ≥2-fold Increases in Antibody Titers From Baseline | Days 29, 181, 365, and 730 | A ≥2-fold increase from baseline was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. Part A PPI Set: a randomly selected subset of participants who: a) received the assigned study drug, b) had RSV immunogenicity titer results at baseline (prior to study drug administration) and at least 1 valid result after the study drug administration at timepoint of interest, and c) had no major protocol deviation affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. |
| Part B: Percentage of Participants With Seroresponse of Serum RSV-A and RSV-B nAb at BD Day 29 Compared to Primary Dose Day 29 | Primary Dose Day 29 and BD Day 29 | Seroresponse was defined as a post-primary dose or post-revaccination titer ≥4 \* LLOQ if Baseline was \<LLOQ or a ≥4-fold increase from baseline if baseline was ≥LLOQ. Part B PP Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized. |
| Part B: GMT of Serum RSV-A and RSV-B nAb at BD Day 1 and BD Day 181 | BD Day 1 and BD Day 181 | Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ replaced by ULOQ. LLOQ = 13 IU/mL, ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part B PP Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized. |
| Part B: GMFR of Serum RSV-A and RSV-B NAb From Pre-primary Dose (Baseline) | BD Day 1, BD Day 29, and BD Day 181 | Antibody values reported as below LLOQ replaced by 0.5 \* LLOQ. Values greater than ULOQ replaced by ULOQ. LLOQ = 13 IU/mL, ULOQ = 259061 IU/mL for RSV-A nAb. LLOQ = 10, ULOQ = 112476 for RSV-B nAb. Part B PP Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized. |
| Part B: Percentage of Participants With Seroresponse of Serum RSV-A and RSV-B Neutralizing Antibodies From Pre-primary Dose (Baseline) | BD Day 1, BD Day 29, and BD Day 181 | Seroresponse was defined as a post-primary dose or post-revaccination titer ≥4 \* LLOQ if Baseline was \<LLOQ or a ≥4-fold increase from baseline if baseline was ≥LLOQ. Part B PP Set: all Part B randomized participants who received both Parts A and B assigned study intervention doses, had RSV immunogenicity titer results at pre-Primary Dose (baseline), had RSV immunogenicity titer results at Primary Dose Day 29, had at least 1 valid result at Revaccination Day 29, and had no major protocol deviations affecting the primary immunogenicity outcomes as determined prior to database lock and unblinding. Participants were analyzed according to the study intervention group to which they were randomized. |
Countries
Argentina, Australia, Bangladesh, Belgium, Canada, Chile, Colombia, Costa Rica, Finland, Germany, Japan, Mexico, New Zealand, Panama, Poland, Puerto Rico, Singapore, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 36814 participants were randomized in Part A (18427 participants in the mRNA-1345 group and 18387 participants in the placebo group). A total of 1510 participants from Part A mRNA-1345 group were randomized into Part B substudy (1005 participants in the mRNA-1345 group and 505 in the placebo group). All enrolled participants were included from both Phase 2 and 3 portions in Part A.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 68.5 years STANDARD_DEVIATION 6.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6117 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 395 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1802 Participants |
| Race/Ethnicity, Customized Race Asian | 2151 Participants |
| Race/Ethnicity, Customized Race Black or African American | 4377 Participants |
| Race/Ethnicity, Customized Race Multiple | 752 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 28 Participants |
| Race/Ethnicity, Customized Race Not Reported | 145 Participants |
| Race/Ethnicity, Customized Race Other | 2009 Participants |
| Race/Ethnicity, Customized Race Unknown | 20 Participants |
| Race/Ethnicity, Customized Race White | 11311 Participants |
| Sex: Female, Male Female | 9057 Participants |
| Sex: Female, Male Male | 9330 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 307 / 18,387 | 301 / 18,427 | 1 / 505 | 0 / 1,005 |
| other Total, other adverse events | 6,916 / 18,316 | 7,080 / 18,369 | 29 / 504 | 48 / 998 |
| serious Total, serious adverse events | 2,745 / 18,316 | 2,773 / 18,369 | 26 / 504 | 29 / 998 |
Outcome results
None listed