| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention of medically attended Respiratory Syncytial Virus-associated lower respiratory tract illness (LRTI) in infants by active immunization of pregnant women |
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| E.1.1.1 | Medical condition in easily understood language |
| Prevention of respiratory tract illness caused by a virus called Respiratory Syncytial Virus |
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| 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 | LLT |
| E.1.2 | Classification code | 10066742 |
| E.1.2 | Term | Respiratory syncytial virus infection prophylaxis |
| E.1.2 | System Organ Class | 100000004865 |
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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 |
Primary Efficacy Objectives – Infant Participants
- To evaluate the efficacy of RSVpreF in reducing the incidence of medically attended lower respiratory tract illness (MA-LRTI) due to RSV.
- To evaluate the efficacy of RSVpreF in reducing the incidence of severe MA-LRTI due to RSV.
Primary Safety Objective – Infant Participants
- To describe the safety of RSVpreF.
Primary Safety Objective – Maternal Participants
- To describe the safety and tolerability of RSVpreF. |
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| E.2.2 | Secondary objectives of the trial |
Secondary Efficacy Objectives – Infant Participants
- To evaluate the efficacy of RSVpreF in reducing the incidence of hospitalization due to RSV.
- To evaluate the efficacy of RSVpreF in reducing the incidence of all cause MA-LRTI. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Maternal Participants
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Healthy women ≥18 and ≤ 49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications.
a. First-trimester data available (data obtained at ≤13 6/7 weeks):
•The date of the first day of the reported LMP may be used to establish the GA if corroborated by a first-trimester ultrasound examination.
•If there is a discrepancy of >5 days between the LMP-determined GA and an ultrasound result at ≤8 6/7 weeks OR the LMP is uncertain/unknown, then the GA should be determined using the first-trimester ultrasound result.
•If there is a discrepancy of >7 days between the LMP-determined GA and an ultrasound result at 9 0/7 to 13 6/7 weeks OR the LMP is uncertain/unknown, then the GA should be determined using the first-trimester ultrasound result.
b. Second-trimester data available (data obtained at 14 0/7 to 27 6/7 weeks):
•The date of the first day of the reported LMP may be used to establish the GA if corroborated by a second-trimester ultrasound result.
•If there is a discrepancy of >7 days between the LMP-determined GA and the ultrasound result at 14 0/7 to 15 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be determined using the second-trimester ultrasound result.
•If there is a discrepancy of >10 days between the LMP-determined GA and the ultrasound result at 16 0/7 to 21 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be determined using the second-trimester ultrasound result.
•If there is a discrepancy of >14 days between the LMP-determined GA and the ultrasound result at 22 0/7 to 27 6/7 weeks OR if the LMP is uncertain/unknown, then the GA should be determined using the second-trimester ultrasound result.
Type of Participant and Disease Characteristics
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Receiving prenatal standard of care based on country requirements. Had an ultrasound examination performed at ≥18 weeks of pregnancy with no significant fetal abnormalities observed, based on the investigator’s judgment.
5. Determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study.
6. Documented negative HIV antibody test, syphilis test, and hepatitis B virus (HBV) surface antigen test during this pregnancy and prior to randomization (Visit 1).
7. Intention to deliver at a hospital or birthing facility where study procedures can be obtained.
8. Expected to be available for the duration of the study and can be contacted by telephone during study participation.
9. Participant is willing to give informed consent for her infant to participate in the study.
Informed Consent
10. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol OR
11. If the maternal participant is illiterate, a thumb printed informed consent must be obtained, which must be signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant has been informed of all pertinent aspects of the study.
Infant Participants
1. Evidence of a signed and dated ICD signed by the parent(s)/legal guardian(s) OR
If the infant participant’s maternal participant/parent(s)/legal guardian(s) is illiterate, a thumbprinted informed consent must have been obtained, which must have been signed and dated by an impartial witness who was present throughout the entire informed consent process confirming that the maternal participant/parent(s)/legal guardian(s) has been informed of all pertinent aspects of the study for herself (maternal participant) and her fetus/infant prior to taking part in the study.
2. Parent(s)/legal guardian(s) willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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| E.4 | Principal exclusion criteria |
Maternal Participants
Participants are excluded from the study if any of the following criteria apply:
Weight:
1. Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.
Medical Conditions:
2. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
3. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the investigational product or any related vaccine.
4. Current pregnancy resulting from in vitro fertilization. Participants known to have used clomiphene citrate and/or letrozole with or without intrauterine insemination (IUI) are permitted.
5. Current pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the participation in and completion of the study, including but not limited to the following (refer to the ISF for further details):
•Preeclampsia, eclampsia, or uncontrolled gestational hypertension.
•Placental abnormality.
•Polyhydramnios or oligohydramnios.
•Significant bleeding or blood clotting disorder.
•Endocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating pregnancy or occurring during pregnancy if uncontrolled at the time of consent.
•Any signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current pregnancy to prevent preterm birth.
6. Prior pregnancy complications or abnormalities at the time of consent, based on the investigator’s judgment, that will increase the risk associated with the participation in and completion of the study, including but not limited to the following:
•Prior preterm delivery ≤34 weeks’ gestation.
•Prior stillbirth or neonatal death.
•Previous infant with a known genetic disorder or significant congenital anomaly.
7. Major illness of the maternal participant or conditions of the fetus that, in the investigator’s judgment, will substantially increase the risk associated with the maternal participant’s participation in, and completion of, the study or could preclude the evaluation of the maternal participant’s response.
8. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including monoclonal antibodies, within the year prior to enrollment.
9. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
Prior/Concomitant Therapy:
10. Participation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study participation.
11. Receipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days within 28 days prior to study enrollment. Prednisone use of <20 mg/day for ≤14 days is permitted. Inhaled/nebulized, intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
12. Current alcohol abuse or illicit drug use.
13. Receipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or planned receipt through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.
Prior/Concurrent Clinical Study Experience:
14. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
Diagnostic Assessments:
Not applicable.
Other Exclusions:
15. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
16. Participants who are breastfeeding at the time of enrollment.
Infant Participants
1. Infant who is a direct descendant (eg, child or grandchild) of the study personnel.
2. Receipt of investigational or approved monoclonal antibodies against RSV.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Safety Endpoints – Maternal Participants
The incidence of:
a. prespecified local reactions within 7 days after vaccination.
b. prespecified systemic events within 7 days after vaccination.
c. AEs from the time of vaccination through 1 month after vaccination.
d. SAEs throughout the study (Visit 1 through the 6-month-postdelivery
study visit).
Primary Efficacy Endpoints – Infant Participants
a. RSV-positive MA-LRTI as confirmed by the EAC:
- occurring within 90 days after birth.
- occurring within 120 days after birth, if the analysis at 90 days meets efficacy criteria.
- occurring within 150 days after birth, if the analysis at 120 days meets efficacy criteria.
- occurring within 180 days after birth, if the analysis at 150 days meets efficacy criteria.
b. Severe MA-LRTIs due to RSV as confirmed by the EAC:
- occurring within 90 days after birth.
- occurring within 120 days after birth, if the analysis at 90 days meets efficacy criteria.
- occurring within 150 days after birth, if the analysis at 120 days meets efficacy criteria.
- occurring within 180 days after birth, if the analysis at 150 days meets efficacy criteria.
Primary Safety Endpoints – Infant Participants
a. Specific birth outcomes.
b. AEs from birth to 1 month of age.
c. SAEs and NDCMCs:
- from birth through 6 months of age (first RSV season for all infant
participants).
- from birth through 12 months of age (for all infant participants).
- from birth through 24 months of age (for infant participants born to
maternal participants enrolled during the first year of the study). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Safety Endpoints – Maternal Participants
a. and b.: within 7 days after vaccination.
c. from the time of vaccination through 1 month after vaccination.
d. throughout the study (Visit 1 through the 6-month-postdelivery study visit).
Primary Efficacy Endpoints – Infant Participants
a. and b.: within 90, 120, 150 and 180 days after birth.
Primary Safety Endpoints – Infant Participants
a.birth
b. from birth to 1 month of age.
c. from birth through 6 months of age (first RSV season for all infant
participants).
- from birth through 12 months of age (for all infant participants).
- from birth through 24 months of age (for infant participants born to maternal participants enrolled during the first year of the study). |
|
| E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints – Infant Participants
a. Hospitalization due to RSV:
- occurring within 90 days after birth.
- occurring within 120 days after birth, if the analysis at 90 days meets efficacy criteria.
- occurring within 150 days after birth, if the analysis at 120 days meets efficacy criteria.
- occurring within 180 days after birth, if the analysis at 150 days meets efficacy criteria.
b. MA-LRTI due to any cause with protocol defined criteria:
- occurring within 90 days after birth.
- occurring within 120 days after birth, if the analysis at 90 days meets efficacy criteria.
- occurring within 150 days after birth, if the analysis at 120 days meets efficacy criteria.
- occurring within 180 days after birth, if the analysis at 150 days meets efficacy criteria. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints – Infant Participants
a. and b.: within 90, 120, 150 and 180 days after birth. |
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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 |
|
| 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 | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
| Australia |
| Brazil |
| Canada |
| Chile |
| Denmark |
| Finland |
| Gambia |
| Japan |
| Korea, Republic of |
| Mexico |
| Netherlands |
| New Zealand |
| South Africa |
| Spain |
| Taiwan |
| United States |
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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
|
last visit of the last infant participant in the study
|
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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 | 27 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 13 |
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