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).
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
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
726
Children's of Alabama
Birmingham, Alabama, United States
University of Alabama at Birmingham Women & Infant Center
Birmingham, Alabama, United States
University of Alabama at Birmingham/Center for Women's Reproductive Health
Birmingham, Alabama, United States
Velocity Clinical Research, Gulfport
Mobile, Alabama, United States
Arrowhead Hospital
Glendale, Arizona, United States
Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 1
Pain at injection site, redness \& swelling were recorded by participants in an electronic diary (e-diary). Redness \& swelling were measured \& recorded in measuring devise units (range 1 to 21) then converted to cm. 1 measuring device unit = 0.5 cm \& graded as mild: \> 2.0 to 5.0 cm, moderate: \> 5.0 to 10.0 cm, severe: \> 10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) \& necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity \& grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Reactions reported as adverse events in the case report form within 7 days after the study vaccination were also included in the analysis. Exact 2-sided 95% confidence interval (CI) was based on Clopper \& Pearson method.
Time frame: From Day 1 to Day 7 after dose 1
Percentage of Maternal Participants Reporting Local Reactions Within 7 Days After Dose 2
Pain at injection site, redness \& swelling were recorded by participants in an e-diary. Redness \& swelling were measured \& recorded in measuring devise units (range 1 to 21) then converted to cm. 1 measuring device unit = 0.5 cm \& graded as mild: \> 2.0 to 5.0 cm, moderate: \> 5.0 to 10.0 cm, severe: \> 10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) \& necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity \& grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Reactions reported as adverse events (AEs) in the case report form (CRF) within 7 days after the study vaccination were also included in the analysis. Exact 2-sided 95% CI was based on the Clopper \& Pearson method.
Time frame: From Day 1 to Day 7 after dose 2
Percentage of Maternal Participants Reporting Systemic Events Within 7 Days After Dose 1
Systemic events were recorded by participants in an e-diary. Fever was oral temperature \>= 38 degree Celsius (°C) \& categorized as \>=38.0 to 38.4 °C, \>38.4 to 38.9 °C, \>38.9 to 40.0 °C \& \>40.0 °C. Fatigue, headache, chills, new or worsened muscle pain \& new or worsened joint pain were graded mild: did not interfere with activity, moderate: some interference with activity \& severe: prevented daily routine activity. Vomiting was graded mild: 1 to 2 times in 24 hours (h), moderate: \>2 times in 24h \& severe: required intravenous hydration. Diarrhea was graded mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h \& severe: 6 or more loose stools in 24h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator/medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also included in analysis. Exact 95% CI was based on Clopper \& Pearson method.
Time frame: From Day 1 to Day 7 after dose 1
Percentage of Maternal Participants Reporting Systemic Events Within 7 Days After Dose 2
Systemic events were recorded by participants in an e-diary. Fever was oral temperature \>= 38 °C \& categorized as \>=38.0 to 38.4 °C, \>38.4 to 38.9 °C, \>38.9 to 40.0 °C \& \>40.0 °C. Fatigue, headache, chills, new or worsened muscle pain \& new or worsened joint pain were graded mild: did not interfere with activity, moderate: some interference with activity \& severe: prevented daily routine activity. Vomiting was graded mild: 1 to 2 times in 24 h, moderate: \>2 times in 24 h \& severe: required intravenous hydration. Diarrhea was graded mild: 2 to 3 loose stools in 24 h, moderate: 4 to 5 loose stools in 24 h \& severe: 6 or more loose stools in 24 h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator/medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also included in analysis. Exact 95% CI was based on Clopper \& Pearson method.
Time frame: From Day 1 to Day 7 after dose 2
Percentage of Maternal Participants With Adverse Events (AEs) From Dose 1 Through 1 Month After Dose 2 - Blinded Follow-up Period
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.
Time frame: From dose 1 on Day 1 through 1 month after dose 2 (approximately 2 months)
Percentage of Maternal Participants Reporting Serious Adverse Events (SAEs) From Dose 1 Through 1 Month After Delivery - Blinded Follow-up Period
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Time frame: From dose 1 on Day 1 through 1 month after delivery (up to 22 weeks)
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
GMR of 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 up to 1 month after Dose 2 was reported in this outcome measure. Geometric mean titer (GMT) and 2-sided 95% CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on student t distribution) and was reported in descriptive section. GMR was reported in statistical analysis section of this outcome measure. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of vaccine to which they were randomized, with Dose 2 received within predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
Time frame: 1 Month after Dose 2
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
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 was reported in this outcome measure. GMT and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the student t distribution) and was reported in the descriptive section. GMR was reported in the statistical analysis section. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of the vaccine to which they were randomized, with Dose 2 received within the predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
Time frame: 1 Month after Dose 2
COVID-19 Incidence Per 100 Person-Years of Blinded Follow up in Evaluable Maternal Participants Without Evidence of Prior SARS-CoV-2 Infection
COVID-19 incidence per 100 person-years of blinded follow-up in evaluable maternal participants without evidence of prior SARS-CoV-2 infection prior to 7 days after receipt of Dose 2 was reported in this outcome measure.
Time frame: From 7 days after Dose 2 up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.155, Placebo- 0.149)
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
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 was reported in this outcome measure.
Time frame: From 7 days after Dose 2 up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.270, Placebo- 0.263)
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
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 prior to the first post-dose 2 N-binding test was reported in this outcome measure.
Time frame: Up to 1 month after delivery (Surveillance time [100 person-year]: BNT162b2- 0.099, Placebo- 0.147)
Geometric Mean Concentration (GMCs) of Full-Length S-Binding Immunoglobulin G (IgG) Levels in Evaluable Maternal Participants
GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMCs of full-length S-binding IgG levels in evaluable maternal participants at baseline, 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery was reported in this outcome measure. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of the vaccine to which they were randomized, with Dose 2 received within the predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
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Abrazo West Campus Hospital
Goodyear, Arizona, United States
St. Joseph Hospital
Phoenix, Arizona, United States
MedPharmics, LLC
Phoenix, Arizona, United States
Matrix Clinical Research.
Huntington Park, California, United States
Matrix Clinical Research
Huntington Park, California, United States
...and 80 more locations
Time frame: Baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
Geometric Mean Titer (GMTs) of SARS-CoV-2 Neutralizing Titers in Evaluable Maternal Participants
GMTs, and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMTs of SARS-CoV-2 neutralizing titers in evaluable maternal participants at baseline, 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery was reported in this outcome measure. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of the vaccine to which they were randomized, with Dose 2 received within the predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
Time frame: Baseline (before Dose 1), 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
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
GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMFR from before vaccination to each subsequent time point after vaccination for full-length S-binding IgG levels in evaluable maternal participants at 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery was reported in this outcome measure. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of the vaccine to which they were randomized, with Dose 2 received within the predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
Time frame: From before dose 1 up to 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
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
GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMFR from before vaccination to each subsequent time point after vaccination for SARS-CoV-2 neutralizing titers in evaluable maternal participants at 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery was reported in this outcome measure. Evaluable immunogenicity population included all participants who were eligible and randomized, received 2 doses of the vaccine to which they were randomized, with Dose 2 received within the predefined window (19-42 days, inclusive, after Dose 1); had at least 1 valid immunogenicity result within an appropriate window 1 month after Dose 2 (28-42 days, inclusive, after Dose 2); and had no other important protocol deviations as determined by the clinician.
Time frame: From before dose 1 up to 2 weeks after Dose 2, 1 month after Dose 2, at delivery, and 6 months after delivery
Percentage of Infant Participants Reporting Specific Birth Outcomes
Percentage of infant participants reporting specific birth outcomes (normal, congenital malformation/anomaly, other neonatal problems) were reported in this outcome measure.
Time frame: At birth
Percentage of Infant Participants Reporting Adverse Events From Birth Through 1 Month of Age
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Time frame: From birth through 1 month of age
Percentage of Infant Participants Reporting Serious Adverse Events (SAE) From Birth Through 6 Months of Age
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Time frame: From birth through 6 months of age
Percentage of Infant Participants Reporting Adverse Event of Special Interest (AESI) From Birth Through 6 Months of Age
Percentage of infant participants who reported AESI including major congenital anomalies and developmental delay from birth through 6 months of age were reported in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method.
Time frame: From birth through 6 months of age
GMCs of Full-Length S-Binding IgG Levels at Birth and 6 Months of Age in Infant Participants Born to Evaluable Maternal Participants
GMCs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMCs of full-length S-binding IgG levels at birth and 6 months of age in infant participants born to evaluable maternal participants was reported in this outcome measure.
Time frame: At birth and 6 months of age
GMFR of Full-Length S-Binding IgG Levels From Birth to 6 Months of Age in Infant Participants Born to Evaluable Maternal Participants
GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. GMFR of full-length S-binding IgG levels from birth to 6 months of age in infant participants born to evaluable maternal participants was reported in this outcome measure.
Time frame: From birth to 6 months of age