| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy Volunteers (prevention of lower respiratory tract illness) |
|
| E.1.1.1 | Medical condition in easily understood language |
| RSV is a common virus that leads to mild, cold-like symptoms in adults and older healthy children. RSV can cause more serious disease in infants, such as inflammation of the lungs. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| 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 |
Safety
•To evaluate the safety and reactogenicity of 2 dose levels (60 and 120 µg) of RSVPreF3 when given alone or co-administered with dTpa from Vaccination up to Day 31.
•To evaluate the safety of a 2nd dose of RSVPreF3 given from 12 up to 18 months post 1st dose up to Day 31 days post 2nd dose vaccination.
Immunogenicity
•To evaluate the humoral immune response to 2 dose levels (60 and 120 µg) of RSVPreF3 when given alone and co-administered with dTpa, at Screening, Day 8 and Day 31 post 1st dose vaccination. |
|
| E.2.2 | Secondary objectives of the trial |
Safety
To evaluate safety of:
•RSVPreF3 (60 & 120µg), given alone & co-administered with dTpa compared to dTpa-Placebo groups from 1st vaccination to Day 181
•RSVPreF3 (pooled for all groups receiving RSVPreF3) for the 1st vaccination
•2nd dose of RSVPreF3 given from 12 up to 18 months post 1st vaccination to Day 181 post 2nd vaccination
To evaluate by formulation:
•Safety & reactogenicity of RSVPreF3 (60 & 120µg) given alone or co-administered with dTpa from 1st Vaccination to Day 31
•Safety of RSVPreF3 (60 & 120µg), given alone & co-administered from 1st Vaccination to Day 181
Immunogenicity
To evaluate humoral immune response:
•of RSVPreF3 (60 & 120µg) given alone & co-administered with dTpa (at Screening, Day 8, Day 31 & at 12 to 18 months) and to pertussis, diphtheria (D) & tetanus (T) components of dTpa vaccine (at Screening & Day 31) - by formulation
•of a 2nd vaccination of RSVPreF3 (120µg), following 1st vaccination (60 or 120µg) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Primary study
•Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
•Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure.
•Healthy female subjects; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
•Female subjects of childbearing potential may be enrolled in the study, if the subject:
-has practiced adequate contraception for 30 days prior to primary vaccination, and
-has a negative pregnancy test on the day of primary vaccination, and
-has agreed to continue adequate contraception for 90 days after completion of the vaccination.
•No local condition precluding injection in both left and right deltoid muscles.
Extension study
•Completed primary study and received 1st dose of a study vaccine.
•Written or witnessed/thumb printed informed consent obtained from the subject prior to performance of any study specific procedure to the study extension.
All subjects must satisfy ALL the following criteria:
•Subjects who can and will comply with the requirements of the protocol.
•Female subjects remain healthy; as established by medical history and clinical examination, aged 18 to 45 years at the time of the 1st vaccination;
•Female subjects of childbearing potential are eligible for the extension, if the subject:
- has practiced adequate contraception for 30 days prior to 2nd vaccination
- has a negative pregnancy test with results available on the day of 2nd vaccination
- has agreed to continue adequate contraception for 90 days after completion of the 2nd vaccination. |
|
| E.4 | Principal exclusion criteria |
Primary study
Medical conditions
•History of any reaction/hypersensitivity likely to be exacerbated by any vaccines’ component
•Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination
•Hypersensitivity to latex
•Major congenital defects
•Acute/chronic clinically significant pulmonary,cardiovascular,hepatic/renal functional abnormality
•Significant/uncontrolled psychiatric illness
•Recurrent history/uncontrolled neurological disorders/seizures
•Documented HIV-positive subject
•History of/current autoimmune disease
•Body mass index (BMI)>40 kg/m^2
•Any clinically significant hematological parameter and/or biochemical laboratory abnormality
•Any other clinical condition that might pose additional risk to the subject due to participation in the study
Prior/Concomitant therapy
•Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before 1st vaccination,or planned use during the study
•Administration of long-acting immune-modifying drugs at any time during the study
•Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st vaccination or planned administration during the study
•Chronic administration of immunosuppressants/other immune-modifying drugs during the period starting 3 months prior to 1st vaccine dose(s).For corticosteroids,this will mean prednisone≥5 mg/day,or equivalent.Inhaled and topical steroids are allowed
•Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 1st vaccination,with the exception of any licensed influenza vaccine which may be administered≥15 days before/after study vaccination
•Administration of a vaccine containing diphtheria, tetanus/pertussis antigens/diphtheria and tetanus toxoids within the previous 5 years
•Previous experimental vaccination against RSV
Prior/Concurrent clinical study experience
•Concurrently participating in another clinical study, at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product
Other exclusions
•Pregnant/lactating female
•Female planning to become pregnant/planning to discontinue contraceptive precautions
•History of alcoholism, drug abuse and/or use disorder within the past 2 years
•Any study personnel/their immediate dependents, family/household members
Extension study
Medical conditions
•History of any reaction/hypersensitivity likely to be exacerbated by any component of the vaccines
•Any confirmed/suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination
•Hypersensitivity to latex
•Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality
•Significant/uncontrolled psychiatric illness
•Recurrent history/uncontrolled neurological disorders/seizures
•Documented HIV-positive subject
•History of/current autoimmune disease
•BMI>40 kg/m^2
•Participants who experienced any SAE judged to be possibly or probably related to 1st dose of RSVPreF3, including hypersensitivity reactions
•Any other clinical condition that might pose additional risk to the subject due to participation in the study
Prior/Concomitant therapy
•Use of any investigational/non-registered product other than the study vaccines during the period starting 30 days before the 2nd vaccination, or planned use during the 6-month study extension
•Administration of long-acting immune-modifying drugs at any time during the study
•Administration of immunoglobulins and/or any blood products/plasma derivatives during the period starting 3 months before the 1st dose of study vaccines/planned administration during the study
•Chronic administration of immunosuppressants or other immune-modifying drugs during the starting 3 months prior to the 1st vaccine dose(s). For corticosteroids, this will mean prednisone≥5 mg/day or equivalent.Inhaled and topical steroids are allowed
•Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after study 2nd vaccination,with the exception of any licensed influenza vaccine which may be administered≥15 days before/after study vaccination
Prior/Concurrent clinical study experience
Concurrently participating in another clinical study,at any time during the study, in which the subject has been/will be exposed to an investigational/a non-investigational vaccine/product
Other exclusions
•Pregnant/lactating female at the time of Visit 4
•Female planning to become pregnant/planning to discontinue contraceptive precautions
•History of alcoholism, drug abuse and/or use disorder within the past 2 years
•Any study personnel/their immediate dependents,family/household members |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Percentage of subjects with at least one solicited local adverse event (AE) for each study group, after the 1st vaccination
An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Solicited local AEs, at the site of injection in both limbs, are: pain, redness and swelling.
2. Percentage of subjects with at least one solicited general AE for each study group, after the 1st vaccination
Solicited general AEs are: fatigue, fever, gastrointestinal symptoms including nausea, vomiting, diarrhea and/or abdominal pain, headache.
3. Percentage of subjects with any unsolicited AEs for each study group, after the 1st vaccination
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.
4. Percentage of subjects with at least one serious adverse event (SAE) for each study group, after the 1st vaccination
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
5. Percentage of subjects with at least one solicited local AE for each study group, after the 2nd vaccination
An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Solicited local AEs, at the site of injection in both deltoids, are: pain, redness and swelling.
6. Percentage of subjects with at least one solicited general AE for each study group, after the 2nd vaccination
Solicited general AEs are: fatigue, fever, gastrointestinal symptoms including nausea, vomiting, diarrhea and/or abdominal pain, headache.
7. Percentage of subjects with any unsolicited AEs for each study group, after the 2nd vaccination
An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited AE.
8. Percentage of subjects with at least one SAE for each study group, after the 2nd vaccination
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
9. Humoral immune response in terms of RSV A neutralizing antibody Geometric Mean Titers (GMTs) for each group, at Screening
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay.
10. RSV A neutralizing antibody GMTs for each group, at Day 8, after the 1st vaccination
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay.
11. RSV A neutralizing antibody GMTs for each group, at Day 31, after the 1st vaccination
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay.
12. Humoral immune response in terms of RSV PreF3 IgG antibody Geometric Mean Concentration (GMCs) for each group, at Screening
Serological assays for the determination of IgG antibodies against RSV PreF3 are performed by Enzyme-linked immunosorbent assay (ELISA). The corresponding antibody GMC is expressed in ELU/mL. The cut-off value for the assay is 25 ELU/mL.
13. RSV PreF3 IgG GMCs for each group, at Day 8, after the 1st vaccination
Serological assays for the determination of IgG antibodies against RSV PreF3 are performed by ELISA. The corresponding antibody GMC is expressed in ELU/mL. The cut-off value for the assay is 25 ELU/mL.
14. RSV PreF3 IgG GMCs for each group, at Day 31, after the 1st vaccination
Serological assays for the determination of IgG antibodies against RSV PreF3 are performed by ELISA. The corresponding antibody GMC is expressed in ELU/mL. The cut-off value for the assay is 25 ELU/mL. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From Day 1 to Day 8
2. From Day 1 to Day 8
3. From Day 1 to Day 31
4. From Day 1 to Day 31
5. From the Day of 2nd vaccination to Day 8 post 2nd vaccination
6. From the Day of 2nd vaccination to Day 8 post 2nd vaccination
7. From the Day of 2nd vaccination to Day 31 post 2nd vaccination
8. From the Day of 2nd vaccination to Day 31 post 2nd vaccination
9. From Day -7 to Day 1
10. At Day 8
11. At Day 31
12. From Day -7 to Day 1
13. At Day 8
14. At Day 31 |
|
| E.5.2 | Secondary end point(s) |
1. Percentage of subjects with at least one solicited local AE for each group and formulation, after the 1st vaccination
For description, please see primary (pri.) end point 1
2. Percentage of subjects with at least one solicited general AE for each group and formulation, after the 1st vaccination
For description, please see pri. end point 2
3. Percentage of subjects with any unsolicited AE, for each group and formulation, after the 1st vaccination
For description, please see pri. end point 3
4. Percentage of subjects with at least one SAE from 1st vaccination to Day 31, for each formulation
For description, please see pri. end point 4
5. Percentage of subjects with at least one SAE from 1st vaccination to Day 181, for pooled formulations
For description, please see pri. end point 4.This outcome measure evaluates the safety of 2 dose levels of RSVPreF3 when given alone and co-administered with dTpa compared to dTpa_Placebo groups.
6. Percentage of subjects with at least one report of SAE from 1st vaccination to Day 181, for each formulation
For description, please see pri. end point 4.This outcome measure evaluates the safety of 2 dose levels of RSVPreF3 when given alone and co-administered.
7. Percentage of subjects with at least one SAE from 1st vaccination to Day 181, for pooled all groups receiving RSVPreF3
For description, please see pri. end point 4.This outcome measure evaluates the safety of all groups receiving RSVPreF3 vaccine.
8. Percentage of subjects with at least one SAE from 2nd vaccination to Day 181 post 2nd vaccination
For description, please see secondary (sec.) end point 6
9. Humoral immune response in terms of RSV A neutralizing GMTs for each formulation, at Screening
Serological assays for the determination of antibodies against RSV-A are performed by neutralization assay.
10. RSV A neutralizing GMTs for each formulation, at Day 8, after the 1st vaccination
For description, please see sec. end point 9
11. RSV A neutralizing GMTs for each formulation, at Day 31, after the 1st vaccination
For description, please see sec. end point 9
12. RSV A neutralizing GMTs for each formulation, at a single timepoint between 12 to 18 months post 1st vaccination
For description, please see sec. end point 9
13. Humoral immune response in terms of RSV PreF3 IgG antibody GMCs for each formulation, at Screening
Serological assays for the determination of IgG antibodies against RSV PreF3 are performed by ELISA. The corresponding antibody concentration is expressed in ELU/mL. The cut-off value for the assay is 25 ELU/mL.
14. RSV PreF3 IgG antibody GMCs for each formulation, at Day 8, after the 1st vaccination
For description, please see sec. end point 13
15. RSV PreF3 IgG antibody GMCs for each formulation, at Day 31, after the 1st vaccination
For description, please see sec. end point 13
16. RSV PreF3 IgG antibody GMCs for each formulation, at a single timepoint between 12 to 18 months post 1st vaccination
For description, please see sec. end point 13
17. Humoral immune response to the pertussis components of the dTpa vaccine in terms of antibody GMCs against pertussis toxoid (anti-PT), filamentous hemagglutinin (anti-FHA) and pertactin (anti-PRN) for each formulation, at Screening
Serological assays for the determination of IgG antibodies against Bordetella pertussis: anti-PT, anti-FHA and anti-PRN are performed by ELISA. The corresponding antibody concentrations are expressed in IU/mL. The cut-off value for the assay for anti-PT is 2.693 IU/mL, for anti-FHA is 2.046 IU/mL and for anti-PRN is 2.187 IU/mL.
18. Anti-PT, anti-FHA and anti-PRN concentrations, for each formulation, at Day 31, after the 1st vaccination
For description, please see sec. end point 17
19. Humoral immune response to the Diphtheria (D) component of the dTpa vaccine in terms of antibody GMCs against D toxoid (anti-D), for each formulation, at Screening
Serological assays for the determination of IgG antibodies against Corynebacterium diphtheriae, anti-D, are performed by ELISA. The corresponding antibody concentration is expressed in IU/mL. The cut-off value for the assay is 0.057 IU/mL.
20. Anti-D antibody GMCs for each formulation, at Day 31, after the 1st vaccination
For description, please see sec. end point 19
21. Anti-T (Tetanus) antibody GMCs for each formulation, at Screening
Serological assays for the determination of IgG antibodies against Clostridium tetani, anti-T, are performed by ELISA. The corresponding antibody concentration is expressed in IU/mL. The cut-off value for the assay is 0.043 IU/mL.
22. Anti-T antibody GMCs for each formulation, at Day 31, after the 1st vaccination
For description, please see sec. end point 21
23. RSV A neutralizing GMTs for each formulation, at Day 31 post 2nd vaccination
For description, please see sec. end point 9
24. RSV PreF3 IgG antibody GMCs for each formulation, at 31 days post 2nd vaccination
For description, please see sec.end point 13 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From Day 1 to Day 8
2. From Day 1 to Day 8
3. From Day 1 to Day 31
4. From Day 1 to Day 31
5. Throughout the study period (From Day 1 to Day 181)
6. From Day 1 to Day 181
7. From Day 1 to Day 181
8. From the Day of 2nd vaccination to Day 181 post 2nd vaccination
9. From Day -7 to Day 1
10. At Day 8
11. At Day 31
12. At a single timepoint between 12 to 18 months post 1st vaccination
13. From Day -7 to Day 1
14. At Day 8
15. At Day 31
16. At a single timepoint between 12 to 18 months post 1st vaccination
17. From Day -7 to Day 1
18. At Day 31
19. From Day -7 to Day 1
20. At Day 31
21. From day -7 to Day 1
22. At Day 31
23. At Day 31 post 2nd vaccination
24. At Day 31 post 2nd vaccination |
|
| 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, Reactogenicity |
|
| 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) | 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 | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 5 |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 |
| Canada |
| United States |
| Belgium |
|
| 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 testing results released of samples collected at Visit 6, to occur no later than 8 months after last subject last visit (LSLV), which occurs with phone contact 3 on Day 181 post 2nd vaccination. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 25 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 25 |
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