| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Respiratory Syncytial Virus Infection | |
| E.1.1.1 | Medical condition in easily understood language | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10061603 | | E.1.2 | Term | Respiratory syncytial virus infection | | E.1.2 | System Organ Class | 10021881 - Infections and infestations | |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | •To evaluate the safety and tolerability of the mRNA 1345 vaccine.
•To evaluate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of a first episode of RSV LRTD as compared with placebo within the period of 14 days post-injection up to 12 months post-injection. | |
| E.2.2 | Secondary objectives of the trial | Key Secondary Efficacy Objectives:
• To evaluate the efficacy of a single dose of mRNA 1345 vaccine in the prevention of a first episode of RSV ARD as compared with placebo within the period of 14 days post-injection up to 12 months post-injection.
• To evaluate the efficacy of a single dose of mRNA-1345 vaccine in the prevention of first hospitalization associated with RSV ARD or RSV LRTD as compared with placebo within the period of 14 days post-injection up to 12 months post-injection.
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. 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 CHF [including heart failure with preserved ejection fraction] and COPD), but should be medically stable as assessed by the following criteria:
o Absence of changes in medical therapy within 1 month due to treatment failure or toxicity
o Absence of medical events qualifying as SAEs within 1 month of the planned study injection on Day 1
o Absence of known, current, and life-limiting diagnoses, which could continue for the duration of the primary efficacy period (12 months from study injection on Day 1) and which, in the opinion of the investigator, would make completion of the protocol unlikely.
2. Body mass index from ≥ 18 kg/m2 to ≤ 35 kg/m2.
3. Willing and able (on both a physical and cognitive basis) to give informed consent prior to study enrollment.
4. Able to comply with study requirements.
| |
| E.4 | Principal exclusion criteria | 1. Participation in another clinical research study where participant has received an investigational product (drug/biologic/device with the exception of investigational RSV products) within 6 months before the planned date of the Day 1 study injection. Current participation in another RSV investigational trial is exclusionary.
2. History of a diagnosis or condition that, in the judgment of the investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as a diagnosis or condition requiring significant changes in management or medication within the 2 months prior to Screening and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition.
3. Reported history of congenital or acquired immunodeficiency, immunosuppressive condition, or immune-mediated disease.
Note: Human immunodeficiency virus (HIV) positive participants with CD4 count ≥ 350 cells/mm3 and an undetectable HIV viral load within the past year (low level variations from 50-500 viral copies which do not lead to changes in antiretroviral therapy) as determined from participant’s medical records, are permitted.
Note: To clarify, participants with stable autoimmune diseases that do not require systemic immunosuppressants (per Exclusion Criteria #9) are permitted.
4. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, psoriasis patches affecting skin over the deltoid areas).
5. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of the mRNA-1345 vaccine or any components of the mRNA-1345 vaccine.
6. Reported history of bleeding disorder that is considered a contraindication to IM injection or phlebotomy.
7. History of a serious reaction to any prior vaccination, or Guillain-Barré syndrome within 6 weeks of any prior influenza immunization.
8. Received or plans to receive any nonstudy vaccine (including authorized or approved vaccines for the prevention of coronavirus disease 2019 [COVID 19] regardless of type of vaccine) within 28 days before or after the Day 1 study injection. Nonstudy vaccination(s) should not be delayed.
9. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study injection. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
10. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study injection or during the study.
11. Acute disease at the time of enrollment (defined as the presence of moderate or severe illness with or without fever, or an oral temperature ≥ 37.8°C (100.0°F) on the planned day of vaccine administration).
12. Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results.
13. Known history of poorly controlled hypertension (per determination of the investigator), or systolic blood pressure > 160 mmHg at the Screening or baseline (Day 1) visit.
14. Known history of hypotension, or systolic blood pressure < 85 mmHg at the Screening or baseline (Day 1) visit.
15. Diastolic blood pressure > 90 mmHg at the Screening or baseline (Day 1) visit.
16. Known uncontrolled disorder of coagulation.
Note: Participants receiving aspirin, clopidogrel, prasugrel, dipyridamole, dabigatran, apixaban, rivaroxaban, or warfarin for cardiovascular prophylaxis or prophylaxis of thromboembolic disease or stroke in the setting of atrial fibrillation and under good control will NOT be excluded.
17. History of myocarditis, pericarditis, or myopericarditis within 2 months prior to Screening. Participants who have not returned to baseline after their convalescent period will also be excluded.
18. Donated ≥ 450 mL of blood products < 14 days prior to Screening.
19. Member of study personnel or is an immediate family member or household member of study personnel. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Safety Endpoint
•Numbers and percentages of participants with solicited local and systemic adverse reactions (ARs) up to 7 days post-injection.
• Unsolicited adverse events (AEs) up to 28 days post-injection.
• Medically attended adverse events (MAAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and AEs leading to withdrawal up to 24 months post-injection.
Efficacy Endpoint
•Vaccine efficacy of mRNA-1345 to prevent a first episode of RSV-LRTD with 2 or more symptoms within the period of 14 days post-injection up to 12 months post-injection.
•Vaccine efficacy of mRNA 1345 to prevent a first episode of RSV LRTD with 3 or more symptoms within the period of 14 days post-injection up to 12 months post-injection.
| |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | Screening
D1 (Baseline)
D8
D15
D29
D60 then Monthly
B181
D365
D546
D730/EOS | |
| E.5.2 | Secondary end point(s) | •Vaccine efficacy of mRNA-1345 to prevent a first episode of RSV-ARD within the period of 14 days post-injection up to 12 months post-injection.
•Vaccine efficacy of mRNA-1345 to prevent first hospitalization associated with RSV-ARD or RSV-LRTD within the period of 14 days post-injection up to 12 months post-injection.
Key Efficacy Endpoints
•Vaccine efficacy of mRNA-1345 to prevent all cause hospitalizations within the period of 14 days post-injection up to 12 months post-injection.
•Vaccine efficacy of mRNA-1345 to prevent all-cause LRTD within the period of 14 days post-injection up to 12 months post-injection.
•Vaccine efficacy of mRNA-1345 to prevent first episode of RSV-LRTD with 3 or more symptoms within the period of 14 days post-injection up to 24 months post-injection.
•Vaccine efficacy of mRNA 1345 to prevent a first episode of RSV-LRTD with 2 or more symptoms within the period of 14 days post-injection up to 24 months post-injection. | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Screening
D1 (Baseline)
D8
D15
D29
D60 then Monthly
B181
D365
D546
D730/EOS | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description | Tolerability
immunogenecity | |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 53 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Argentina | | Bangladesh | | Chile | | Colombia | | Costa Rica | | New Zealand | | Panama | | Singapore | | Puerto Rico | | Taiwan | | Australia | | Canada | | Japan | | Korea, Republic of | | Mexico | | South Africa | | United Kingdom | | United States | | Belgium | | Finland | | Germany | | Poland | | Spain | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 25 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 25 |
