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

• ClinicalTrials.gov Identifier: NCT04754594
• Recruitment Status: Completed
• First Posted: February 15, 2021
• Last Update Posted: July 13, 2023
• Sponsor: BioNTech SE
• Collaborator: Pfizer
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: February 9, 2021
• First Posted Date: February 15, 2021
• Last Update Posted Date: July 13, 2023
• Actual Study Start Date: February 16, 2021
• Actual Primary Completion Date: July 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 15, 2022)

• Percentage of maternal participants reporting: Local reactions [ Time Frame: For 7 Days after Dose 1 and Dose 2 ]
  Pain at the injection site, redness, and swelling as self-reported on electronic diaries
• Percentage of maternal participants reporting systemic events [ Time Frame: For 7 days after Dose 1 and Dose 2 ]
  Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
• Percentage of maternal participants reporting adverse events [ Time Frame: From Dose 1 through 1 month after Dose 2 ]
  As elicited by investigational site staff
• Percentage of maternal participants reporting serious adverse events [ Time Frame: From Dose 1 through 6 months after delivery ]
  As elicited by investigational site staff
• 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. [ Time Frame: 1 month after Dose 2 ]
  GMR, estimated by the ratio of the geometric mean of SARS CoV 2 neutralizing titers in pregnant women to those in nonpregnant female participants
• 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 [ Time Frame: 1 month after Dose 2 ]
  GMR, estimated by the ratio of the geometric mean of SARS CoV 2 neutralizing titers in pregnant women to those in nonpregnant female participants

Original Primary Outcome Measures (submitted: February 11, 2021)

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

Current Secondary Outcome Measures (submitted: August 3, 2022)

• Confirmed COVID 19 in participants without evidence of infection prior to vaccination [ Time Frame: 7 days after Dose 2 through 1 month after delivery ]
  1000 person years of follow-up
• Confirmed COVID 19 in participants with and without evidence of infection prior to vaccination [ Time Frame: 7 days after Dose 2 through 1 month after delivery ]
  1000 person years of follow-up
• Describe the efficacy of prophylactic BNT162b2 against asymptomatic SARS-CoV-2 infection without evidence of prior SARS-CoV-2 infection [ Time Frame: 1 month after delivery ]
  Incidence of asymptomatic infection of SARS-CoV-2 based on N-binding antibody seroconversion
• Describe the immune response over time and persistence of prophylactic BNT162b2 [ Time Frame: At baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery ]
  GMCs/GMTs and GMFRs of Full-length S-binding IgG levels and SARS-CoV-2 neutralizing titers
• Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy [ Time Frame: At birth ]
  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)
• Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy [ Time Frame: From birth through 1 month of age ]
  AEs
• Assess the safety of maternal immunization in infants born to maternal participants who were vaccinated with BNT162b2 during pregnancy [ Time Frame: Through 6 months of age ]
  SAEs and AESIs (major congenital anomalies, developmental delay)
• Describe the immune response in infants born to maternal participants vaccinated with prophylactic BNT162b2 during pregnancy [ Time Frame: At birth and 6 months after delivery ]
  GMCs and GMFRs of Full-length S-binding IgG levels

Original Secondary Outcome Measures (submitted: February 11, 2021)

• Confirmed COVID 19 in participants without evidence of infection prior to vaccination [ Time Frame: 7 days after Dose 2 through 1 month after delivery ]
  1000 person years of follow-up
• Confirmed COVID 19 in participants with and without evidence of infection prior to vaccination. [ Time Frame: 7 days after Dose 2 through 1 month after delivery ]
  1000 person years of follow-up

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention

Condition

• SARS-CoV-2 Infection
• COVID-19
• Maternal Immunization

Intervention

• Biological: BNT162b2
  Intramuscular Injection
• Other: Placebo
  Intramuscular Injection

Study Arms

• Experimental: BNT162b2
  2 doses
  Intervention: Biological: BNT162b2
• Placebo Comparator: Placebo
  2 doses
  Intervention: Other: Placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 12, 2023): 683
• Original Estimated Enrollment (submitted: February 11, 2021): 4000
• Actual Study Completion Date: July 15, 2022
• Actual Primary Completion Date: July 15, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, South Africa, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04754594
• Other Study ID Numbers: C4591015; 2020-005444-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: Same as current
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: Same as current
• Collaborators: Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: BioNTech SE
• Verification Date: July 2023