| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteer (prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV)) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Healthy volunteer (prevention of lower respiratory tract disease caused by RSV) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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 |
Cohorts 1 and 2:
-To assess the safety and reactogenicity of various combinations of RSV vaccine components
-To assess humoral immune responses elicited by various combinations of RSV vaccine components
Cohort 3:
-To assess the safety and reactogenicity of the selected RSV.preF-based vaccine formulation (based on Cohort 1 and 2 results), compared to the formulation to be used for future clinical development
Cohort 4:
-To assess immune responses, including durability to the selected RSV.preF-based vaccine formulation (formulation for future clinical development) in groups with and without revaccination |
|
| E.2.2 | Secondary objectives of the trial |
Cohorts 1 and 2:
-To assess humoral and cellular immune responses elicited by various combinations of RSV vaccine components using other immunological assays
Cohort 3:
-To assess immune responses to the selected RSV.preF-based vaccine formulation (based on Cohort 1 and 2 results), compared to the formulation to be used for future clinical development
-To assess the durability of the immune response to the selected RSV.preF-based vaccine formulation in groups with and without revaccination
Cohort 4:
-To assess the safety and reactogenicity of the selected RSV.preF-based vaccine formulation (formulation for future clinical development) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. aged 60 years or older on the day of signing the ICF and expected to be available for the duration of the study.
2. before randomization, a participant must be:
- postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and
- not intending to conceive by any methods.
3. participant must be in stable health at the time of vaccination. Participants may have underlying illnesses such as hypertension, congestive heart failure, COPD, Type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant’s healthcare provider. Participants will be included on the basis of physical examination, medical history, and vital signs performed between ICF signature and vaccination
4. For participants in Cohorts 1 and 2 only: Participant must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the laboratory screening tests are outside the laboratory normal reference ranges and additionally within the limits of toxicity Grade 2 according to the US FDA toxicity tables, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant and appropriate and reasonable for the population under study. This determination must be recorded in the participant’s source documents and initialed by the investigator
5. agrees not to donate blood from the time of vaccination through 3 months after vaccination |
|
| E.4 | Principal exclusion criteria |
1. history of malignancy within 5 years before screening not in the following categories:
a. Participants with squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix may be enrolled at the discretion of the investigator.
b. Participants with a history of malignancy within 5 years before screening, with minimal risk of recurrence per investigator’s judgment, can be enrolled.
2. known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine)
3. abnormal function of the immune system resulting from:
a. Clinical conditions (eg, autoimmune disease or immunodeficiency) expected to have an impact on the immune response elicited by the study vaccine. Participants with autoimmune disease (eg, autoimmune-mediated thyroid disease, autoimmune inflammatory rheumatic disease such as rheumatoid arthritis, and Type 1 diabetes) that is stable and inactive without the use of systemic immunomodulators and glucocorticoids may be enrolled at the discretion of the investigator.
b. Chronic or recurrent use of systemic corticosteroids within 2 months before administration of study vaccine and during the study. A substantially immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg of prednisone or equivalent.
c. Administration of antineoplastic and immunomodulating agents, eg, cancer chemotherapeutic agents, or radiotherapy within 6 months before administration of study vaccine and during the study
4. per medical history, participant has chronic active hepatitis B or hepatitis C infection.
5. per medical history, participant has HIV type 1 or type 2 infection.
6. history of acute polyneuropathy (eg, Guillain-Barré syndrome) or chronic idiopathic demyelinating polyneuropathy.
7. received hematopoietic stem cell transplant in medical history, treatment with immunoglobulins expected to impact the vaccine-induced immune response (including monoclonal antibodies for chronic underlying conditions) in the 2 months, immunoglobulins specific to RSV, human metapneumovirus, or parainfluenza viruses in the 12 months, apheresis therapies in the 4 months, or blood products in the 4 months before the planned administration of the first study vaccine or has any plans to receive such treatment during the study
8. history of TTS or heparin-induced thrombocytopenia and thrombosis (HITT).
9. received or plans to receive:
a. Licensed live attenuated vaccines within 28 days before or after planned administration of study vaccination
b. Other licensed (not live) vaccines within 14 days before or after planned administration of study vaccination.
10. received or plans to receive a SARS-CoV-2 vaccine:
a. Live attenuated SARS-CoV-2 vaccine within 28 days before or after planned administration of the first or subsequent study vaccines.
b. Non-live SARS-CoV-2 vaccine within 14 days before or after planned administration of the first or subsequent study vaccines.
c. A viral-vectored SARS-CoV-2 vaccine within 6 months prior to randomization or during the study period until 28 days after the last study vaccination.
11. received an RSV vaccine in a previous RSV vaccine study at any time prior to randomization.
12. received or plans to receive an Ad26-vectored vaccine at any time prior to randomization until 28 days after the last study vaccination
13. has taken any disallowed therapies before vaccination.
14. received an investigational drug or used an invasive investigational medical device within 30 days or received an investigational vaccine within 6 months before the planned administration of the study vaccine or is currently enrolled or plans to participate in another investigational study during this study.
15. has a serious chronic disorder, eg, severe chronic obstructive pulmonary disease or severe congestive heart failure, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer’s disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
16. had major surgery (per the investigator’s judgment) within 4 weeks before vaccination, or will not have fully recovered from surgery at time of vaccination (in the opinion of the investigator), or has major surgery planned during the time the participant is expected to participate in the study.
17. contraindication to IM injections and blood draws (eg, bleeding disorders)
18. has had major psychiatric illness and/or drug or alcohol abuse which in the investigator’s opinion would compromise the participant’s safety and/or compliance with the study procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Cohorts 1, 2 and 3:
- Serious adverse events (SAEs) and adverse events of special interest (AESIs) from first dose administration until 6 months after vaccination
- Solicited local and systemic adverse events (AEs) for 7 days after vaccine administration
- Unsolicited AEs from the time of vaccine administration through the following 28 days
Cohorts 1, 2 and 4:
- RSV neutralization antibody titers |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs up to Days 7 and 28 after vaccine administration
SAEs and AESIs until 6 months after vaccination
RSV neutralization antibody titers:
- Cohorts 1 & 2: Days 1, 15, 29, 85, 183, 365, 730, 1095
- Cohort 4: Days 1, 15, 29, 85, 183, 730, 1095, 1460, 1825; Day of Vaccination 2 and Days 14, 28, 84, 182 post-Vaccination 2 |
|
| E.5.2 | Secondary end point(s) |
Cohorts 1 and 2:
F protein binding antibodies (pre-F and/or post-F), and antigen-specific T-cell responses
Cohort 3:
- RSV neutralization antibody titers
Cohort 4:
- SAEs and AESIs from first administration until 6 months after the last vaccination
- Solicited local and systemic AEs for 7 days after each vaccine administration
- Unsolicited AEs from the time of each vaccine administration through the following 28 days |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
AEs up to Days 7 and 28 after vaccine administration
SAEs and AESIs until 6 months after vaccination
F protein binding antibodies (pre-F and/or post-F): Days 1, 15, 29, 85, 183, 365, 730, 1095
Antigen-specific T-cell responses: Days 1, 15, 85, 183, 365, 730, 1095
RSV neutralization antibody titers: Days 1, 15, 29, 85, 183, 730, 1095, 1460, 1825; Day of Vaccination 2 and Days 14, 28, 84, 182 post-Vaccination 2 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| 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 |
| Immunogenicity and reactogenicity |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 19 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| 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 |
| United States |
| Spain |
| Belgium |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| Last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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