Clinical trial NCT04754594: To Evaluate the Safety, Tolerability, and Immunogenicity of BNT162b2 Against COVID-19 in Healthy Pregnant Women 18 Years of Age and Older
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2 Infection
COVID-19
Maternal Immunization
Keywords: SARS-CoV-2 Infection
COVID-19
Maternal Immunization
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2021-02-15
Enrollment: 726
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Healthy participants who are determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study
4. Documented negative HIV antibody test (Phase 2 only), syphilis test, and HBV surface antigen test during this pregnancy and prior to randomization
5. Participant is willing to give informed consent for her infant to participate in the study
6. Capable of giving signed informed consent

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Participants with known or suspected immunodeficiency.
5. Bleeding diathesis or condition associated with prolonged bleeding that would in the opinion of the investigator contraindicate intramuscular injection.
6. Previous vaccination with any coronavirus vaccine.
7. Receipt of medications intended to prevent COVID 19.
8. 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.
9. Current alcohol abuse or illicit drug use.
10. 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.
11. Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
12. Previous participation in other studies involving study intervention containing LNPs.
13. 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.
14. 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.

Primary outcomes:
measure: Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 1
timeFrame: From Day 1 to Day 7 after dose 1
measure: Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 2
timeFrame: From Day 1 to Day 7 after dose 2
measure: Percentage of Maternal Participants Reporting Systemic Events Within 7 Days After Dose 1
timeFrame: From Day 1 to Day 7 after dose 1
measure: Percentage of Maternal Participants Reporting Systemic Events Within 7 Days After Dose 2
timeFrame: From Day 1 to Day 7 after dose 2
measure: Percentage of Maternal Participants With Adverse Events (AEs) From Dose 1 Through 1 Month After Dose 2 - Blinded Follow-up Period
timeFrame: From dose 1 on Day 1 through 1 month after dose 2 (approximately 2 months)
measure: Percentage of Maternal Participants Reporting Serious Adverse Events (SAEs) From Dose 1 Through 1 Month After Delivery - Blinded Follow-up Period
timeFrame: From dose 1 on Day 1 through 1 month after delivery (up to 22 weeks)
measure: Geometric Mean Ratio (GMR) of the SARS-CoV-2 Neutralizing Titers in Pregnant Women to Those in Nonpregnant Women From Study C4591001 (NCT04368728) for Evaluable Immunogenicity Population Without Evidence of Prior SARS-CoV-2 Infection
timeFrame: 1 Month after Dose 2
measure: GMR of SARS-CoV-2 Neutralizing Titers in Pregnant Women to Those in Nonpregnant Women From Study C4591001 (NCT04368728) for Evaluable Immunogenicity Population With and Without Evidence of Prior SARS-CoV-2 Infection
timeFrame: 1 Month after Dose 2
Secondary outcomes:
measure: COVID-19 Incidence Per 100 Person-Years of Blinded Follow up in Evaluable Maternal Participants Without Evidence of Prior SARS-CoV-2 Infection
timeFrame: From 7 days after Dose 2 up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.155, Placebo- 0.149)
measure: COVID-19 Incidence Per 100 Person-Years of Blinded Follow up in Evaluable Maternal Participants With or Without Evidence of Prior SARS-CoV-2 Infection
timeFrame: From 7 days after Dose 2 up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.270, Placebo- 0.263)
measure: Incidence of Asymptomatic Infection of SARS-CoV-2 Through 1 Month After Delivery in Evaluable Maternal Participants Without Evidence of Prior SARS-CoV-2 Infection
timeFrame: Up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.099, Placebo- 0.147)
measure: Geometric Mean Concentration (GMCs) of Full-Length S-Binding Immunoglobulin G (IgG) Levels in Evaluable Maternal Participants
timeFrame: Baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
measure: Geometric Mean Titer (GMTs) of SARS-CoV-2 Neutralizing Titers in Evaluable Maternal Participants
timeFrame: Baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
measure: Geometric Mean Fold Rise (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination for Full-Length S-Binding IgG Levels in Evaluable Maternal Participants
timeFrame: From before dose 1 up to 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
measure: Geometric Mean Fold Rise (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination for SARS-CoV-2 Neutralizing Titers in Evaluable Maternal Participants
timeFrame: From before dose 1 up to 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
measure: Percentage of Infant Participants Reporting Specific Birth Outcomes
timeFrame: At birth
measure: Percentage of Infant Participants Reporting Adverse Events From Birth Through 1 Month of Age
timeFrame: From birth through 1 month of age
measure: Percentage of Infant Participants Reporting Serious Adverse Events (SAE) From Birth Through 6 Months of Age
timeFrame: From birth through 6 months of age
measure: Percentage of Infant Participants Reporting Adverse Event of Special Interest (AESI) From Birth Through 6 Months of Age
timeFrame: From birth through 6 months of age
measure: GMCs of Full-Length S-Binding IgG Levels at Birth and 6 Months of Age in Infant Participants Born to Evaluable Maternal Participants
timeFrame: At birth and 6 months of age
measure: GMFR of Full-Length S-Binding IgG Levels From Birth to 6 Months of Age in Infant Participants Born to Evaluable Maternal Participants
timeFrame: From birth to 6 months of age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Women & Infant Center
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/Center for Women's Reproductive Health
state: Alabama
city: Mobile
country: United States
facility: Velocity Clinical Research, Gulfport
state: Alabama
city: Glendale
country: United States
facility: Arrowhead Hospital
state: Arizona
city: Goodyear
country: United States
facility: Abrazo West Campus Hospital
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph Hospital
state: Arizona
city: Phoenix
country: United States
facility: MedPharmics, LLC
state: Arizona
city: Huntington Park
country: United States
facility: Matrix Clinical Research.
state: California
city: Huntington Park
country: United States
facility: Matrix Clinical Research
state: California
city: Lancaster
country: United States
facility: Chemidox Clinical Trials Inc.
state: California
city: Los Angeles
country: United States
facility: East LA Doctors Hospital
state: California
city: Los Angeles
country: United States
facility: Matrix Clinical Research
state: California
city: Loxahatchee Groves
country: United States
facility: Axcess Medical Research
state: Florida
city: Ammon
country: United States
facility: Idaho Falls Pediatrics
state: Idaho
city: Blackfoot
country: United States
facility: Bingham Memorial Hospital
state: Idaho
city: Idaho Falls
country: United States
facility: Idaho Falls Pediatrics
state: Idaho
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Idaho Falls
country: United States
facility: Eastern Idaho Regional Medical Center
state: Idaho
city: Idaho Falls
country: United States
facility: Mountain View Hospital
state: Idaho
city: Saginaw
country: United States
facility: Covenant Healthcare
state: Michigan
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group, LLC
state: Michigan
city: Anaconda
country: United States
facility: Community Hospital of Anaconda
state: Montana
city: Butte
country: United States
facility: Boeson Research (BUT)
state: Montana
city: Butte
country: United States
facility: SCL St. James Healthcare Hospital
state: Montana
city: Hamilton
country: United States
facility: Marcus Daly Memorial Hospital
state: Montana
city: Missoula
country: United States
facility: Providence St. Patrick Hospital
state: Montana
city: Missoula
country: United States
facility: The Birth Center
state: Montana
city: Missoula
country: United States
facility: Boeson Research
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Physicians Group-Maternal Fetal Medicine
state: Montana
city: Ronan
country: United States
facility: St. Luke Community Healthcare Hospital
state: Montana
city: Hastings
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research, LLC
state: Nebraska
city: Erie
country: United States
facility: Allegheny Health and Wellness Pavilion
state: Pennsylvania
city: Erie
country: United States
facility: OBGYN Associates of Erie
state: Pennsylvania
city: Erie
country: United States
facility: Central Erie Primary Care
state: Pennsylvania
city: Erie
country: United States
facility: Liberty Family Practice
state: Pennsylvania
city: Erie
country: United States
facility: Saint Vincent Hospital
state: Pennsylvania
city: Austin
country: United States
facility: St. David's Medical Center
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc.
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc.
state: Texas
city: Bedford
country: United States
facility: Texas Health Harris Methodist Hospital Hurst-Euless-Bedford
state: Texas
city: Dallas
country: United States
facility: Ventavia Research Group LLC
state: Texas
city: Edinburg
country: United States
facility: DHR Health Institute for Research and Development
state: Texas
city: Fort Worth
country: United States
facility: 8th Avenue Obstetrics & Gynecology
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott & White All Saints Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: McAllen
country: United States
facility: Dr. Ruben Aleman & Associates
state: Texas
city: Plano
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: Weatherford
country: United States
facility: Ventavia Research Group, LLC
state: Texas
city: Weatherford
country: United States
facility: Weatherford OBGYN
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: The Group for Women- MAWC
state: Virginia
city: Norfolk
country: United States
facility: Tidewater Physicians for Women- MAWC
state: Virginia
city: Belo Horizonte
country: Brazil
facility: Faculdade de Medicina da Universidade Federal de Minas Gerais
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas da Universidade Federal de Minas Gerais
state: Minas Gerais
city: Sorocaba
country: Brazil
facility: Hospital Santa Casa de Misericordia de Sorocaba
state: SAO Paulo
city: Sorocaba
country: Brazil
facility: Unimed Sorocaba-Hospital Dr. Miguel Soeiro (HMS)
state: SAO Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila S/S Ltda./ CMPC - Consultoria Medica e Pesquisa Clinica
state: SP
city: São Bernardo do Campo
country: Brazil
facility: HMU SBC - Hospital Municipal Universitário de São Bernardo
state: SÃO Paulo
city: São Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
state: SÃO Paulo
city: Benoni
country: South Africa
facility: WorthWhile Clinical Trials
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute (Wits RHI) Shandukani Research Centre
state: Gauteng
city: Pretoria
country: South Africa
facility: Botho Ke Bontle Health Services
state: Gauteng
city: Soweto
country: South Africa
facility: Vaccines and Infectious Diseases Analytics (VIDA)
state: Gauteng
city: Cape Town
country: South Africa
facility: Dr Tobias de Villiers
state: Western CAPE
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre CC
state: Western CAPE
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: Boadilla del Monte
country: Spain
facility: Hospital Universitario HM Monteprincipe
state: Madrid
city: Antequera
country: Spain
facility: Hospital de Antequera
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Clinica Diagonal
city: Mostoles
country: Spain
facility: Hospital Madrid Puerta del Sur Mostoles
city: Sevilla
country: Spain
facility: Instituto Hispalense de Pediatria- IHP1
city: Sevilla
country: Spain
facility: Hospital Materno-Infantil Quirón
city: Sevilla
country: Spain
facility: Servicio de Ginecología del Hospital Quirón Salud Sagrado Corazón
city: Southampton
country: United Kingdom
facility: Hampshire Research Hub, Royal South Hants Hospital
state: Hampshire
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
state: Kent
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: University College London Hospitals
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Nana M, Hodson K, Lucas N, Camporota L, Knight M, Nelson-Piercy C. Diagnosis and management of covid-19 in pregnancy. BMJ. 2022 Apr 26;377:e069739. doi: 10.1136/bmj-2021-069739.
citation: Mohapatra S, Ananda P, Tripathy S. Pharmacological consideration of COVID-19 infection and vaccines in pregnancy. J Chin Med Assoc. 2022 May 1;85(5):537-542. doi: 10.1097/JCMA.0000000000000712. Epub 2022 May 2.