To Evaluate the Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older

Study Overview
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Brief Summary
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Results will be submitted, however please note that data are not yet available for all serology outcome measures. This will be a Phase 2/3, randomized, placebo-controlled, observer-blind study evaluating the safety, tolerability, and immunogenicity of 30 µg of BNT162b2 or placebo administered in 2 doses, 21 days apart, in approximately 350 healthy pregnant women 18 years of age or older vaccinated at 24 to 34 weeks' gestation. Participants will be randomized 1:1 to receive BNT162b2 or placebo (saline).

Detailed Description
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The Phase 2 portion of the study will include approximately 200 pregnant women randomized 1:1 to receive BNT162b2 or placebo (saline) at 27 to 34 weeks' gestation. IRC review of safety data through 7 days after the second dose for all Phase 2 participants will be completed. The Phase 3 portion of this study will assess the safety, tolerability, and immunogenicity of BNT162b2 among pregnant women enrolled at 24 to 34 weeks' gestation. Maternal participants who originally received placebo will receive BNT162b2 at defined time points as part of the study.

Official Title
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A PHASE 2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE (BNT162b2) AGAINST COVID-19 IN HEALTHY PREGNANT WOMEN 18 YEARS OF AGE AND OLDER

Conditions
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COVID-19, SARS-CoV-2 Infection, Maternal Immunization

Intervention / Treatment
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* Biological: BNT162b2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy women ≥18 years of age who are between 24 0/7 and 34 0/7 weeks' gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Healthy participants who are determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study Documented negative HIV antibody test (Phase 2 only), syphilis test, and HBV surface antigen test during this pregnancy and prior to randomization Participant is willing to give informed consent for her infant to participate in the study Capable of giving signed informed consent Exclusion Criteria: Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID 19. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention or any related vaccine. Participants with known or suspected immunodeficiency. Bleeding diathesis or condition associated with prolonged bleeding that would in the opinion of the investigator contraindicate intramuscular injection. Previous vaccination with any coronavirus vaccine. Receipt of medications intended to prevent COVID 19. Receipt of blood/plasma products or immunoglobulin, from 60 days before administration of study intervention, or planned receipt through delivery, with 1 exception, anti-D immunoglobulin (eg, RhoGAM), which can be given at any time. Current alcohol abuse or illicit drug use. Participants who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt through the postvaccination blood draw. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation. Previous participation in other studies involving study intervention containing LNPs. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. Participants whose unborn baby has been fathered by investigational site staff members directly involved in the conduct of the study or their family members, site staff members otherwise supervised by the investigator, or Pfizer employees directly involved in the conduct of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BNT162b2<br>2 doses | Biological: BNT162b2<br>* Intramuscular Injection<br>|
| Placebo Comparator: Placebo<br>2 doses | Other: Placebo<br>* Intramuscular Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of maternal participants reporting: Local reactions | Pain at the injection site, redness, and swelling as self-reported on electronic diaries | For 7 Days after Dose 1 and Dose 2 | 
| Percentage of maternal participants reporting systemic events | Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries. | For 7 days after Dose 1 and Dose 2 | 
| Percentage of maternal participants reporting adverse events | As elicited by investigational site staff | From Dose 1 through 1 month after Dose 2 | 
| Percentage of maternal participants reporting serious adverse events | As elicited by investigational site staff | From Dose 1 through 6 months after delivery | 
| Describe the immune response in pregnant women and reference to the immune response to nonpregnant female participants from the C4591001 study without evidence of past SARS-CoV-2 infection. | GMR, estimated by the ratio of the geometric mean of SARS CoV 2 neutralizing titers in pregnant women to those in nonpregnant female participants | 1 month after Dose 2 | 
| Describe the immune response in pregnant women and reference to the immune response in nonpregnant female participants from the C4591001 study with and without evidence of prior SARS-CoV-2 infection | GMR, estimated by the ratio of the geometric mean of SARS CoV 2 neutralizing titers in pregnant women to those in nonpregnant female participants | 1 month after Dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed COVID 19 in participants without evidence of infection prior to vaccination | 1000 person years of follow-up | 7 days after Dose 2 through 1 month after delivery | 
| Confirmed COVID 19 in participants with and without evidence of infection prior to vaccination | 1000 person years of follow-up | 7 days after Dose 2 through 1 month after delivery | 
| Describe the efficacy of prophylactic BNT162b2 against asymptomatic SARS-CoV-2 infection without evidence of prior SARS-CoV-2 infection | Incidence of asymptomatic infection of SARS-CoV-2 based on N-binding antibody seroconversion | 1 month after delivery | 
| Describe the immune response over time and persistence of prophylactic BNT162b2 | GMCs/GMTs and GMFRs of Full-length S-binding IgG levels and SARS-CoV-2 neutralizing titers | At baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery | 
| Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy | Specific birth outcomes (infant outcome using percentage of births clinically assessed as either normal, congenital malformation/anomaly or other neonatal problem as reported by the investigator) | At birth | 
| Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy | AEs | From birth through 1 month of age | 
| Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy | SAEs and AESIs (major congenital anomalies, developmental delay) | Through 6 months of age | 
| Describe the immune response in infants born to maternal participants vaccinated with prophylactic BNT162b2 during pregnancy | GMCs and GMFRs of Full-length S-binding IgG levels | At birth and 6 months after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 Infection, COVID-19, Maternal Immunization