| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| High risk pregnant women (prevention of RSV-associated lower respiratory tract illnesses (LRTIs) in infants) |
|
| E.1.1.1 | Medical condition in easily understood language |
| RSV is a very common virus that leads to mild, cold-like symptoms in adults and 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 |
• To evaluate the safety and reactogenicity of a single IM dose of study intervention administered to maternal participants up to 42 days post-delivery.
• To evaluate the pregnancy outcomes and pregnancy-related AESIs up to 42 days post-delivery, in maternal participants who received a single IM dose of study intervention .
• To evaluate safety up to 42 days post-birth in infants born to maternal participants who received a single IM dose of study intervention.
• To evaluate the safety of the vaccine in infants up to 365 days post-birth.
• To evaluate the immunogenicity of a single IM dose of study intervention administered to maternal participants, at delivery.
• To evaluate the transfer of RSV-specific antibodies from maternal participants who received a single IM dose of study intervention to their infants at delivery.
• To evaluate the RSV-specific antibody levels at birth in infants born to maternal participants who received a single IM dose of study intervention. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the safety of the vaccine in mothers up to 180 days post-delivery.
• To evaluate the worsening of pre-existing medical conditions and/or obstetric complications up to 180 days post-delivery.
• To evaluate the occurrence of RSV-associated MA-RTIs in maternal participants up to 180 days post-delivery.
• To evaluate the occurrence of RSV-associated LRTIs in infants up to 365 days post-birth.
• To evaluate the occurrence of RSV-associated hospitalization in infants up to 365 days post-birth.
• To evaluate the immunogenicity of the vaccine in maternal subjects up to delivery.
• To evaluate neutralizing antibody titers against RSV-B in infants at birth.
• To evaluate RSV-specific antibodies up to Day 181 post-birth in infants. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Maternal participants
• Participants who can and will comply with the requirements of the protocol.
• Participants and LARs who give written or witnessed/thumb printed informed consent after the study has been explained according to local regulatory requirements, and before any study specific procedures are performed. The informed consent given at screening should either:
- include consent for both the maternal participant’s participation* and participation of the infant after the infant’s birth, or
- include consent for the maternal participant’s participation* and expressed willingness to consider permitting the infant to take part after the infant’s birth (if local regulations/guidelines require parent(s) to provide an additional informed consent after the infant’s birth).
- both mother and father should consent if local regulations / guidelines require it.
• Pre-pregnancy Body Mass Index (based on participant’s report) 18.5 to 39.9 kg/m^2, inclusive.
• Healthy adolescent pregnant women, 15 to 17 YOA, inclusive, at the time of study intervention administration.
OR
• Pregnant women, 18 to 49 YOA, inclusive, at the time of study intervention administration with:
- HIV infection
AND/OR
- Obstetric complications or risk factors during the current pregnancy, where the expectant management of the pregnancy is possible and without evidence of non-reassuring fetal status (only cases for which fetal heart rate can be ascertained) as follows:
- Gestational diabetes, well-controlled on medications (with or without diet or exercise)
- Gestational hypertension, well-controlled on diet or medications below 160/110 mmHg.
- Pre-eclampsia without severe features (i.e. eclampsia, severe hypertension [>160/110 mmHg], organ dysfunction, unstable or complicated by [HELLP] syndrome).
- Fetal Growth Restriction in singleton pregnancies, with normal umbilical artery Doppler and estimated fetal weight 3 to 10th percentile for gestational age.
- History of threatened preterm labor in the current pregnancy, with no cervical dilation greater than 2 cm or effacement exceeding 50%, and/or no progressive change in cervical dilation or effacement detected by serial examinations, when maternal participant is asymptomatic
- Uncomplicated twin gestation.
• Pregnant females at 24^0/7 to 36^0/7 weeks of gestation at the time of study intervention administration (Day 1), as established by:
- Last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S) (i.e. at or before 28 weeks of gestation).
- first or second trimester U/S only, if LMP is unknown/uncertain.
- Certain LMP, corroborated by an U/S performed after 28 weeks of gestation is also acceptable.
The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) gestation age assessment tool
• Participants who are willing to provide cord blood.
• Willing to have their offspring followed-up after delivery for a period of 12 months.
• Participants who do not plan to give their offspring for adoption or place the child in care.
Note that women whose pregnancies resulted from Assisted Reproductive Technologies may be enrolled if they meet all inclusion criteria and none of the exclusion criteria.
Infant participants
• Live-born from the study pregnancy.
• If required per local regulations / guidelines, re-signed (confirmed) written or witnessed/thumb printed informed consent for study participation of the infant obtained from the infant’s mother and/or father and/or LAR, before performing any infant study specific procedure. To comply with RTI surveillance and other protocol required procedures that begin immediately after birth: if written consent cannot be provided by the parent(s)/LAR(s) readily post-birth, verbal consent – if permitted per local regulation -- may be sought from the parent(s) / LAR(s) instead. Verbal consent should be documented in the source data by the investigator or delegate. The parent(s) / LAR(s) will provide additional, written informed consent by (or before) Visit 2-NB. |
|
| E.4 | Principal exclusion criteria |
Maternal participants
Medical conditions
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
• Hypersensitivity to latex.
• Any pre-existing medical conditions or obstetric complications in the current pregnancy that, are poorly controlled and/or with clinical evidence of a non-reassuring fetal status and/or are likely to result in delivery within 7 days after study intervention administration and/or when the timing of planned delivery is within 7 days after study intervention administration and/or acute conditions requiring immediate medical attention for maternal stabilization and/or treatment.
• A multiple pregnancy with 3 or more fetuses.
• Complicated twin gestation.
• Placenta Accreta Spectrum, including placenta increta, percreta, and accreta.
• Fetal structural defects or genetic abnormalities that affect (or are likely to affect) fetal health or survival during the first year of life.
• Known or suspected impairment of the immune system or immunodeficiency syndrome other than HIV.
• Lymphoproliferative disorder or malignancy within 5 years before study dose administration.
• Any illness of the mother or conditions of the fetus that, may substantially interfere with the maternal participant’s ability to comply with study procedures, or could increase the risks to the mother or the fetus, or could preclude the evaluation of the participant's data.
• Any other clinical condition that, might pose additional risk to the participant due to participation in the study, as determined by medical history, physical examination or laboratory screening tests.
• Women with any diagnosis, condition, treatment, or other factor that, has the potential to affect or confound assessments of immunogenicity or safety
• Any conditions which, in the investigator’s opinion, would increase the risks of study participation to the unborn infant.
Prior/Concomitant therapy
• Prior receipt of an RSV maternal vaccine.
• Use of any investigational or non-registered product other than the study intervention(s) during the period beginning:
- For a drug, vaccine or medical device: 29 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
- For immunoglobulins: 90 days before the dose of study intervention(s), or their planned use during the study period.
The exception to this is investigational products administered in the setting of a pandemic. Administration in this case should respect the same period outlined above prior to study intervention administration, but may be allowed following delivery.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 29 days before the study Day 1 and ending at delivery, with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap – alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B vaccines, all of which may be administered according to standard of care ≥ 15 days before or after study intervention (Day 1).
• Receipt of blood or plasma products or immunoglobulin, from 90 days before study intervention administration, or planned receipt through delivery, with the exception of Rho(D) immunoglobulin, which can be given at any time. In that sense, COVID-19 vaccines may be allowed, when administered ≥ 15 days before or after study vaccination.
• Administration of immune-modifying therapy within 6 months before study intervention administration, or planned administration through delivery, except if it is part of management of HIV infection.
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 intervention.
Other exclusions
• Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of major roles to use, withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving.
• A local condition that precludes injection of the study vaccine/product or precludes assessment of local (administration site) reactogenicity.
• Consanguinity of maternal participant and her partner.
• Any study personnel or their immediate dependents, family, or household members.
Infant participants
• Concurrently participating in another clinical trial, 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.
• Any condition which, would increase the risks of study participation to the infant.
• Child in care. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Percentage of maternal participants reporting solicited administration site events
2. Percentage of maternal participants reporting solicited systemic events
3. Percentage of maternal participants reporting unsolicited adverse events (AEs)
4. Percentage of maternal participants reporting serious adverse events (SAEs), (S)AEs leading to study withdrawal, and medically attended adverse events (MAEs)
5. Percentage of maternal participants reporting pregnancy outcomes
6. Percentage of maternal participants reporting pregnancy-related adverse events of special interest (AESIs)
7. Percentage of maternal participants reporting worsening of pre-existing medical conditions and/or obstetric complications from Day 1 up to 42 days post-delivery
8. Percentage of infant participants reporting neonatal / infant AESIs
9. Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
10. Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
11. Percentage of infant participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
12. Humoral immune response in terms of RSV MAT immunoglobulin G (IgG)-specific antibody concentrations at pre-dosing (Day 1) for maternal participants
13. Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at delivery for maternal participants
14. Humoral immune response in terms of RSV-A neutralizing antibody titers at pre-dosing (Day 1) for maternal participants
15. Humoral immune response in terms of RSV-A neutralizing antibody titers at delivery for maternal participants
16. Geometric Mean Ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations.
17. Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at delivery for infant participants
18. Humoral immune response in terms of RSV-A neutralizing antibody titers at delivery for infant participants |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 2. From Day 1 to Day 7 included
3. From Day 1 to Day 30 included
4, 5, 6, 7. From Day 1 up to 42 days post-delivery
8, 9. From birth up to 42 days post-birth
10. From birth up to 180 days post-birth
11. From birth up to 365 days post-birth
12, 14. At Day 1 (pre-dosing)
13, 15, 16, 17, 18. At delivery |
|
| E.5.2 | Secondary end point(s) |
1. Percentage of maternal participants reporting SAEs, (S)AEs leading to study withdrawal, and MAEs
2. Percentage of maternal participants reporting worsening of pre-existing medical conditions and/or obstetric complications from Day 1 post-dosing up to 180 days post-delivery
3. Percentage of maternal participants reporting RSV-associated medically attended respiratory tract illnesses (MA-RTIs)
4. Percentage of infant participants reporting medically assessed, RSV-associated LRTIs
5. Percentage of infant participants reporting medically assessed, RSV-associated hospitalizations
6. Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at Day 31 post-dosing for maternal participants
7. Humoral immune response in terms of RSV-A neutralizing antibody titers at Day 31 post-dosing for maternal participants
8. Humoral immune response in terms of RSV-B neutralizing antibody titers at pre-dosing (Day 1), Day 31 post-dosing and delivery for maternal participants
9. Humoral immune response in terms of RSV-B neutralizing antibody titers at delivery for infant participants
10. Humoral immune response in terms of RSV MAT IgG-specific antibody concentrations at Day 43, Day 121 and Day 181 post-birth for infant participants
11. Humoral immune response in terms of RSV-A neutralizing antibody titers at Day 43, Day 121 and Day 181 post-birth for infant participants
12. Humoral immune response in terms of RSV-B neutralizing antibody titers at Day 43, Day 121 and Day 181 post-birth for infant participants |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3. From Day 1 up to 180 days post-delivery
2. From Day 1 post-dosing up to 180 days post-delivery
4, 5. From birth up to 365 days post-birth
6, 7. At Day 31 post-dosing
8. At pre-dosing (Day 1), Day 31 post-dosing and delivery
9. At delivery
10, 11, 12. At Day 43, Day 121 and Day 181 post-birth |
|
| 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 |
Immune response
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) | 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 | Yes |
| 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 |
| The study was unblinded to ensure the participant’s safety. |
|
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
| Brazil |
| Canada |
| India |
| Panama |
| South Africa |
| United States |
| Finland |
| Italy |
| 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
|
| End of Study (EoS) occurs with the last infant participant last visit (LSLV; Visit 5-NB). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 16 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 16 |
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