E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus Infection |
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E.1.1.1 | Medical condition in easily understood language |
Respiratory syncytial virus infection is caused by RSV, which causes respiratory tract infections in people of all ages. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 | 10035732 |
E.1.2 | Term | Pneumonia respiratory syncytial viral |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 | 10038718 |
E.1.2 | Term | Respiratory syncytial virus bronchiolitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 | 10069811 |
E.1.2 | Term | Respiratory syncytial virus bronchitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10035692 |
E.1.2 | Term | Pneumonia due to respiratory syncytial virus |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067384 |
E.1.2 | Term | Respiratory syncytial virus pneumonitis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052200 |
E.1.2 | Term | Respiratory syncytial virus infection NOS |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066741 |
E.1.2 | Term | Respiratory syncytial virus infection recurrent |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
•Demonstrate the efficacy of a single dose of the RSVPreF3 OA vaccine in preventing RSV-confirmed LRTD during the first season in adults ≥60 YOA. |
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E.2.2 | Secondary objectives of the trial |
• Demonstrate efficacy of RSVPreF3 OA vaccine following a single and annual revaccination doses in preventing: - RSV-confirmed LRTD over several seasons & for each RSV subtype - LRTD caused by other respiratory pathogens over 3 seasons •Evaluate efficacy of RSVPreF3 OA vaccine after 1 dose and annual revaccination doses in preventing: -RSV-confirmed LRTD by age, season, year, baseline comorbidities & frailty status, & for each RSV subtype, severity, RSV-confirmed ARI, LRTD caused by other respiratory pathogens; hospitalization due to respiratory diseases; complications related to RSV-confirmed ARI & any ARI during RSV seasons; Any ARI & any LRTD •Evolution of efficacy of single dose of study vaccine in preventing RSV-confirmed LRTD •Impact of the study vaccine after 1 dose and annual revaccination doses on LRT symptoms, ARI total symptoms, health utility score, physical functioning •Describe RSV-confirmed ARI & LRTD cases •Humoral immune response, reactogenicity & safety |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•A male or female ≥ 60 YOA at the time of the first vaccination, who live in the general community (community dwelling participants) or in a long-term care facility (LTCF) (LTCF participants). •Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Note: In case of physical incapacity that would preclude the self-completion of the diary cards and/or questionnaires, either site staff can assist the participant (for activities performed during site visits) or the participant may assign a caregiver to assist him/her with this activity (for activities performed at home or in the LTCF). However, at no time, the site staff or caregiver will evaluate the participant’s health status while answering diaries and/or questionnaires or make decisions on behalf of the participant •Written or witnessed informed consent obtained from the participant prior to performance of any study specific procedure. •Participants who are medically stable in the opinion of the investigator at the time of first vaccination. Participants with chronic stable medical conditions with or without specific treatment, such as diabetes, hypertension or cardiac disease, are allowed to participate in this study if considered by the investigator as medically stable. |
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E.4 | Principal exclusion criteria |
Medical conditions •Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy, based on medical history and physical examination (no laboratory testing required). •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. •Hypersensitivity to latex. •Serious or unstable chronic illness. •Any history of dementia or any medical condition that moderately or severely impairs cognition. Note: If deemed necessary for clinical evaluation, the investigator can use tools such as Mini-Mental State Exam (MMSE), Mini-Cog or Montreal Cognitive Assessment (MoCA) to determine cognition levels of the participant. •Recurrent or un-controlled neurological disorders or seizures. Participants with medically-controlled active neurological diseases can be enrolled in the study as per investigator assessment, provided that their condition will allow them to comply with the requirements of the protocol. •Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study. •Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Prior/Concomitant therapy •Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine during the period beginning 30 days before the first dose of study vaccine administration, or planned use during the study period. •Planned or actual administration of a vaccine not foreseen by the study protocol in the period starting 30 days before each dose and ending 30 days after each dose of study vaccine administration, with the exception of inactivated and subunit influenza vaccines which can be administered up to 14 days before or from 14 days after each study vaccination. •Previous vaccination with an RSV vaccine. •Administration of long-acting immune-modifying drugs or planned administration at any time during the study period. •Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 90 days before the first study vaccine or planned administration during the study period. •Chronic administration (defined as more than 14 consecutive days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first study vaccine administration or planned administration during the study period. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Prior/Concurrent clinical study experience •Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device). Other exclusions •History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential participant unable/unlikely to provide accurate safety reports or comply with study procedures. •Bedridden participants. •Planned move during the study period that will prohibit participating in the trial until study end. This includes: -Planned move during the study period to another LTCF that will prohibit participation in the trial until study end. -Planned move from the community to a LTCF that will prohibit participation in the trial until study end. •Participation of any study personnel or their immediate dependants, family, or household members. •Planned leave or holiday of 4 consecutive weeks or more during the RSV seasons* covered by the study, that would prohibit the reporting of ARI cases and attendance to ARI visit. *RSV seasons are from October to April in NH and from March to September in SH. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of participants with first episode of RT-PCR confirmed RSV A and/or B associated LRTD during the first season following a single dose of the RSVPreF3 OA vaccine in adults ≥ 60 YOA |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From 2 weeks post-first vaccination until the efficacy data lock point for analysis, triggered by at least 56 cases accrued (assessed approximately over 7 to 10 months) |
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E.5.2 | Secondary end point(s) |
*Number (No.) of participants with 1st episode of RT-PCR confirmed 1)*RSV A &/or B associated LRTD over several seasons** 2)*RSV A &/or B associated LRTD over several seasons*** 3)*RSV subtype A&B LRTD over 3 seasons** 4)*RSV subtype A&B LRTD over 3 seasons*** 5)*LRTD caused by other respiratory pathogens over 3 seasons** 6)*LRTD caused by other respiratory pathogens over 3 seasons*** 7)*RSV subtype A&B LRTD**** 8)*LRTD caused by other respiratory pathogens**** 9)*RSV A &/or B associated LRTD, by age categories**** 10)*RSV A &/or B associated LRTD by RSV season**** 11)*RSV A &/or B associated LRTD by year**** 12)*RSV A &/or B associated LRTD** 13)*RSV A &/or B associated LRTD by baseline comorbidities**** 14)*RSV A &/or B associated LRTD by baseline frailty status**** 15)*RSV A &/or B associated severe LRTD**** 16)*RSV A &/or B associated ARI**** 17)No. of participants with 1st episode of any ARI or any LRTD**** 18)No. of hospitalizations due to respiratory diseases or due to a complication related to respiratory diseases, during the RSV seasons**** 19)No. of hospitalizations due to RSV-confirmed respiratory diseases or due to complication related to RSV-confirmed respiratory diseases, during the RSV seasons**** 20)No. of complications related to ARI & RSV-confirmed ARI during the RSV seasons**** 21)Maximum Influenza Patient- Reported Outcome (Flu-PRO) Chest score for the participants with RT-PCR-confirmed RSV A &/or B-associated ARI**** 22)Least Square Mean Flu-PRO total score for the participants with RT-PCR-confirmed RSV A &/or B-associated ARI**** 23)EuroQol 5-dimension health questionnaire (EQ-5D) utility score for participants with RT-PCR-confirmed RSV A &/or B-associated ARI**** 24)Short Form-12 (SF-12) physical functioning score for participants with RT-PCR confirmed RSV A &/or B-associated ARI**** 25)Duration of RT-PCR confirmed RSV A &/or B ARI & LRTD episodes 26)No. of participants with each reported symptom/sign of RT-PCR confirmed RSV A &/or B ARI & LRTD episodes 27)No. of participants with RT-PCR confirmed RSV A &/or B ARI & LRTD episodes according to severity 28)RSVPreF3 specific immunoglobulin G(IgG) antibody concentrations 29)RSV A neutralizing antibody titers 30)RSV B neutralizing antibody titers 31)No. of participants with any, grade 3 solicited administration site events 32)No. of participants with any, grade 3 solicited systemic events 33)No. of days with solicited administrative site & systemic events 34)No. of participants with any unsolicited AEs 35)No. of participants with Serious Adverse Events (SAEs) 36)No. of participants with potential Immune Mediated Diseases (pIMDs) 37)No. of participants with related SAEs & fatal SAEs 38)No. of participants with related pIMDs **following a single dose of the RSVPreF3 OA vaccine ***following annual revaccination (revacc.) doses of the RSVPreF3 OA vaccine ****following a single dose of the RSVPreF3 OA vaccine & following annual revacc. doses
Timeframes: 1)2 weeks (wks) post 1st vacc. over several seasons (*****) 2)2 wks post each revacc. dose over several seasons (*****) 3,5)2 wks post 1st vacc. over 3 seasons (*****) 4,6)2 wks post each revacc. dose over 3 seasons (*****) 7)2 wks post 1st & each revacc. dose to the 1st occurrence of LRTD caused by RSV A&B subtype (*****) 8)2 wks post 1st & each revacc. dose to the 1st occurrence of LRTD caused by other respiratory pathogens (*****) 9,13,14,15)2 wks post 1st & each revacc. dose to the 1st occurrence of RSV LRTD (*****) 10)start of the RSV season to the 1st occurrence of RSV-confirmed LRTD at each RSV season (assessed approximately over 7 months at each season) 11)2 wks post 1st & each revacc. dose until end of year 1, 2&3 12)2 wks post 1st vacc. to 1st occurrence of RSV LRTD over time (*****) 16)2 wks post 1st & each revacc. dose to 1st occurrence of RSV ARI (*****) 17)2 wks post 1st & each revacc. dose to the 1st occurrence of any ARI or any LRTD (*****) 18,19,20)During the 3 RSV seasons in NH & at least 2 RSV seasons in SH (approximately 7 months for each season) 21,22)During the 1st 7 days from the onset of ARI symptoms 23, 24)At the ARI visit (assessed from 2 wks post 1st & each revacc. dose until end of study- ******) 25,26,27)Assessed during the study period (******) 28,29,30)At Day 1, Day 31, pre-season 2&3 31,32,33)During the 4-day follow up period after each vacc. (*******) 34)During the 30-day follow up period after each vacc. (*******) 35,36)From the day of the vacc. up to 6 months after each vacc. (*******) 37,38)From Day 1 up to study end (******) *****assessed approximately over 3 years in NH & 2.5-3 years in SH ******approximately 3 years in NH & 2.5-3 years in SH *******vaccine or placebo administered on Day 1, pre-season 2&3-only applicable for participants in NH |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Due to the character limitation, timeframes for secondary endpoints are added after the endpoints in section E.5.2 |
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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 |
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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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 13 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
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 |
Australia |
Canada |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
South Africa |
United States |
Belgium |
Estonia |
Finland |
Hungary |
Poland |
United Kingdom |
Spain |
Czechia |
Germany |
Italy |
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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
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End of Study (EoS): Release of the last testing results of samples collected at the last ARI visit. In these cases, EoS must be achieved no later than 8 months after Last Participant Last Visit (Visit 7NH/Visit 5SH). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 6 |