Clinical trial NCT05031468: Multisite Observational Maternal and Infant Study for COVID-19
Official title: Observational, Prospective Cohort Study of the Immunogenicity and Safety of SARS-CoV-2 Vaccines Administered During Pregnancy or Postpartum and Evaluation of Antibody Transfer and Durability in Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Keywords: Immunization
Pregnancy
Lactation
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2021-09-02
Enrollment: 562
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant individuals and postpartum individuals (within 2 months of delivery) who will be or have been vaccinated with a licensed or EUA SARS-CoV-2 vaccine, and their infants will be enrolled. Individuals receiving additional SARS-CoV-2 vaccine (beyond the primary series) during pregnancy will also be enrolled. Upon delivery, the infants born to individuals who received vaccine during pregnancy will become study participants.

Brief summary: This is an observational, non-interventional, prospective cohort study designed to collect clinical information and specimens to evaluate the immune responses from pregnant individuals and postpartum individuals and their infants following maternal receipt of licensed or Emergency Use Authorization (EUA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines.

Detailed description: SARS-CoV-2, the novel coronavirus that causes Coronavirus Disease 2019 (COVID-19) disease, first emerged in Wuhan, China in December 2019 and has continued to spread globally. SARS-CoV-2 is highly transmissible between humans. A number of public health measures, including social distancing, avoidance of large congregations, particularly indoors, and the wearing of face masks, have been introduced to prevent spread of the virus. However, once these measures are relaxed, unless population immunity exceeds herd immunity thresholds, recrudescence of SARS-CoV-2 is expected. This underscores the urgent need for a safe and effective SARS-CoV-2 vaccine.

While all vaccines in late-stage development are based on the SARS-CoV- 2 S glycoprotein, they differ in other important characteristics, including manufacturing platform, number of doses, and immunogenicity and safety profiles. Two messenger RNA (mRNA)-based vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (NIAID-Moderna) were granted Emergency Use Authorization (EUA) by the U.S. FDA based on high demonstrated efficacy against symptomatic infection and severe disease in diverse populations. Janssen (Johnson \& Johnson) was also granted EUA for their single dose nonreplicating adenovirus vector vaccine. None of these large vaccine trials enrolled pregnant or lactating women (except for a small number of lactating women who were enrolled in the Janssen study).

The mRNA vaccines are being distributed to prioritized population groups, and other vaccines are expected to follow as they receive EUA approval. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) gave a permissive recommendation for pregnant individuals who are in a priority group to receive SARS-CoV-2 vaccines based on risk of exposure or comorbidities. In addition, some states have included pregnant individuals in priority groups based on pregnancy itself being considered a high-risk condition by CDC. Thus, pregnant individuals are choosing to receive these vaccines under EUA, without trial data on safety and efficacy. There are neither data on the safety of SARS-CoV-2 vaccines in lactating women nor on the effects of mRNA or other vaccines on the breastfed infant or on milk production/excretion. Current EUA vaccines are not thought to be a risk to the breastfeeding infant.

Currently, additional doses of SARS-CoV-2 vaccines are being considered to enhance durability and breadth of protection, particularly against variant strains. On August 25, 2021, Pfizer submitted a supplement to their Biologics License Application (BLA) for their mRNA vaccine seeking approval for administration of an additional dose, and other manufacturers are expected to follow. In the setting of this rapidly evolving regulatory and policy environment, it is important that data on kinetics and durability of maternal and infant antibodies be generated for all vaccine regimens, including any additional doses beyond the primary series that may be administered to pregnant women.

Vaccines for pregnant individuals, such as influenza, tetanus and pertussis vaccines, are one of the most important public health measures globally to reduce disease in both mothers and infants in the first months of life. Various organizations support the position that pregnant and lactating women are a priority population and must not be excluded from the SARS-CoV-2 vaccine allocation strategy.

The purpose of this study is to evaluate the immunogenicity and safety of various licensed or EUA SARS-CoV-2 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in infants. The researchers will also evaluate the durability of the antibodies in mothers and infants and assess breast milk antibodies in lactating women. The researchers will evaluate breast milk antibodies to assess potential for protection against COVID-19 in breastfed infants, similar to influenza vaccine protection from influenza illness in infants of mothers vaccinated during pregnancy or postpartum. The researchers anticipate including up to 3 vaccines, whether given as part of the primary series or additional doses, as part of this non-interventional study. It is expected that the results of this study will inform policy recommendations and personal decision-making on the use of approved SARS-CoV-2 vaccines in pregnant and lactating individuals.

This is an observational, non-interventional, prospective cohort study designed to collect clinical information and specimens to evaluate the immune responses from approximately 2,000 study participants following maternal receipt of licensed or EUA SARS-CoV-2 vaccines. Participants receiving a SARS-CoV-2 vaccine either during pregnancy or within 2 months of delivery, and their infants, will be followed for 12 months after delivery.

Eligibility criteria: Inclusion Criteria for Pregnancy Group (Group 1):

* Pregnant individuals who are scheduled to receive or have received complete vaccination series of any licensed or EUA SARS-CoV-2 vaccine during pregnancy. (NOTE: no limitation health status, or gestational age at enrollment)
* Willing and able to provide consent for study participation for herself and for her infant prior to initiation of any study procedures.

Inclusion Criteria for Postpartum Group (Group 3):

* Individuals who are scheduled to receive or who have initiated vaccination series of any licensed or EUA SARS-CoV-2 vaccine within the first 2 months postpartum. (NOTE: no limitation on health status).
* Willing and able to provide consent for study participation for herself and for her infant prior to initiation of any study procedures (a separate consent form will be used for their infants).

Inclusion Criteria for Additional Dose(s) During Pregnancy Group (Group 5):

* Pregnant individuals who received one dose or both doses of their primary vaccine series prior to pregnancy and are scheduled to receive or have received additional dose(s) of any licensed or EUA SARS-CoV-2 vaccine during pregnancy OR pregnant individuals who received complete vaccination series during pregnancy and are scheduled to receive or have received additional dose(s) of any licensed or EUA SARS-CoV-2 vaccine during pregnancy. (NOTE: no limitation on health status or gestational age at enrollment). This applies to individuals who have completed their primary series and receive an additional dose during pregnancy.
* Willing and able to provide consent for study participation for herself and for her infant prior to initiation of any study procedures.

Inclusion Criteria for All Participants:

* ≥18 years of age at time of enrollment
* Understands and agrees to comply with all study procedures.
* Agrees to sign medical release for herself and her infant to allow study staff to gather pertinent medical information, pregnancy outcome data, and medical information as needed.

Exclusion Criteria:

* Behavioral (including a history of alcohol or drug abuse within 1 year prior to study enrollment) or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
* Any condition which, in the opinion of the investigators, may pose a health risk to the subject or interfere with the evaluation of the study objectives.

Primary outcomes:
measure: Change in Geometric Mean Titer (GMT) of Serum Immunoglobulin G (IgG) Among Individuals Vaccinated During Pregnancy
timeFrame: Baseline, 28 days post-vaccination, at delivery, postpartum months 2, 6, and 12
measure: Change in GMT of Neutralizing (Neut) Antibodies in Serum Among Individuals Vaccinated During Pregnancy
timeFrame: Baseline, 28 days post-vaccination, at delivery, postpartum months 2, 6, and 12
measure: GMT of Cord Blood IgG
timeFrame: At delivery
measure: Ratio of Cord Blood IgG to Maternal Serum IgG
timeFrame: At delivery
measure: Neut antibodies of cord blood
timeFrame: At delivery
measure: Ratio of cord blood Neut antibodies to maternal serum Neut antibodies
timeFrame: At delivery
measure: Change GMT of serum IgG in Infants Born to Individuals Vaccinated During Pregnancy
timeFrame: At delivery, 2 months of age, 6 months of age
measure: Change GMT of Neut antibodies in Infants Born to Individuals Vaccinated During Pregnancy
timeFrame: At delivery, 2 months of age, 6 months of age
Secondary outcomes:
measure: Frequency of Maternal Outcomes
timeFrame: At delivery
measure: Frequency of Infant Outcomes
timeFrame: At delivery
measure: GMT of Serum IgG Compared to Non-Pregnant Women
timeFrame: 28 days post-vaccination
measure: GMT of Neut Antibodies Compared to Non-Pregnant Women
timeFrame: 28 days post-vaccination
measure: GMT of Serum IgG by Gestational Age at Vaccination
timeFrame: 28 days post-vaccination
measure: GMT of Neut Antibodies by Gestational Age at Vaccination
timeFrame: 28 days post-vaccination
measure: GMT of Serum IgG by Baseline Characteristics
timeFrame: 28 days post-vaccination
measure: GMT of Neut Antibodies by Baseline Characteristics
timeFrame: 28 days post-vaccination
measure: GMT of Cord Blood IgG by Gestational Age at Vaccination
timeFrame: At delivery
measure: Ratio of Cord Blood IgG to Maternal Serum IgG by Gestational Age at Vaccination
timeFrame: At delivery
measure: GMT of Cord Blood Neut Antibodies by Gestational Age at Vaccination
timeFrame: At delivery
measure: Ratio of Cord Blood Neut Antibodies to Maternal Serum Neut Antibodies by Gestational Age at Vaccination
timeFrame: At delivery
measure: GMT of Cord Blood IgG by Baseline Characteristics
timeFrame: At delivery
measure: Ratio of Cord Blood IgG to Maternal Serum IgG by Baseline Characteristics
timeFrame: At delivery
measure: GMT of Cord Blood Neut Antibodies by Baseline Characteristics
timeFrame: At delivery
measure: Ratio of Cord Blood Neut Antibodies to Maternal Serum Neut Antibodies by Baseline Characteristics
timeFrame: At delivery
measure: Change in GMT of IgG in Breast Milk
timeFrame: 2 weeks postpartum, and 2, 6, and 12 months postpartum
measure: Change in GMT of Immunoglobulin A (IgA) in Breast Milk
timeFrame: 2 weeks postpartum, and 2, 6, and 12 months postpartum
measure: Change in GMT of Neut Antibodies in Breast Milk
timeFrame: 2 weeks postpartum, and 2, 6, and 12 months postpartum
measure: Change in GMT of Serum IgG Among Individuals Vaccinated Postpartum
timeFrame: Baseline, 28 days post-vaccination, postpartum months 2, 6, and 12
measure: Change in GMT of Neutralizing (Neut) Antibodies in Serum Among Individuals Vaccinated Postpartum
timeFrame: Baseline, 28 days post-vaccination, postpartum months 2, 6, and 12
measure: Change GMT of serum IgG in Infants Born to Individuals Vaccinated Postpartum
timeFrame: 2 months of age, 6 months of age
measure: Change GMT of Neut antibodies in Infants Born to Individuals Vaccinated Postpartum
timeFrame: 2 months of age, 6 months of age
measure: Change in GMT of Serum IgG Among Individuals Receiving Additional Vaccine Dose(s)
timeFrame: Baseline, 28 days post-vaccination, postpartum months 2, 6, and 12
measure: Change in GMT of Neut Antibodies Among Individuals Receiving Additional Vaccine Dose(s)
timeFrame: Baseline, 28 days post-vaccination, postpartum months 2, 6, and 12
Other outcomes:
measure: Incidence of COVID-19 Infection Among Pregnant Individuals
timeFrame: Up to postpartum month 12
measure: Severity of COVID-19 Infection Among Pregnant Individuals
timeFrame: Up to postpartum month 12
measure: Incidence of COVID-19 Infection Among Infants
timeFrame: Up to 12 months of age
measure: Severity of COVID-19 Infection Among Infants
timeFrame: Up to 12 months of age
measure: Incidence of COVID-19 Infection Among Breastfed Infants
timeFrame: Up to 12 months of age
measure: Severity of COVID-19 Infection Among Breastfed Infants
timeFrame: Up to 12 months of age
measure: Incidence of COVID-19 Infection Among Breastfed Infants by Vaccination Timing
timeFrame: Up to 12 months of age
measure: Severity of COVID-19 Infection Among Breastfed Infants by Vaccination Timing
timeFrame: Up to 12 months of age
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: New York
country: United States
facility: New York University Langone Vaccine Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC) Magee - Womens Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Baylor College of Medicine
name: Flor Munoz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Munoz FM, Beigi RH, Posavad CM, Richardson BA, Chu HY, Bok K, Campbell J, Cardemil C, DeFranco E, Frenck RW, Makhene M, Piper JM, Sheffield J, Miller A, Neuzil KM. Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol. BMC Pregnancy Childbirth. 2022 May 12;22(1):402. doi: 10.1186/s12884-022-04500-w.
citation: Munoz FM, Posavad CM, Richardson BA, Badell ML, Bunge K, Mulligan MJ, Parameswaran L, Kelly C, Olsen-Chen C, Novak RM, Brady RC, Pasetti M, DeFranco E, Gerber JS, Shriver M, Suthar MS, Moore K, Coler R, Berube B, Kim SH, Piper JM, Miller A, Cardemil C, Neuzil KM, Beigi R; DMID Study Group. COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004). medRxiv [Preprint]. 2022 Jun 13:2022.06.13.22276354. doi: 10.1101/2022.06.13.22276354.
citation: Cardemil CV, Cao Y, Posavad CM, Badell ML, Bunge K, Mulligan MJ, Parameswaran L, Olson-Chen C, Novak RM, Brady RC, DeFranco E, Gerber JS, Pasetti M, Shriver M, Coler R, Berube B, Suthar MS, Moreno A, Gao F, Richardson BA, Beigi R, Brown E, Neuzil KM, Munoz FM; MOMI-Vax Study Group. Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants. Pediatrics. 2024 Mar 1;153(3):e2023064252. doi: 10.1542/peds.2023-064252.