Study on the Safety and Immunogenicity of Boostrix Vaccine in Pregnant Malian Women and Their Infants

• ClinicalTrials.gov Identifier: NCT03589768
• Recruitment Status: Completed
• First Posted: July 18, 2018
• Last Update Posted: June 24, 2021
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

This is a phase II, randomized, double-blind, active-controlled study to evaluate the safety, immunogenicity, and effect on infant immune responses of a single dose of Tetanus diphtheria acellular pertussis vaccine (Tdap) in pregnant women in Mali. 200 healthy pregnant women, ages 18 through 39 years, inclusive, who meet all eligibility criteria will be randomly allocated in a 2:1 ratio to receive either Tdap (BOOSTRIX) or Tetanus diphtheria toxoid (Td) at 14 0/7 weeks through 26 6/7 weeks estimated Gestational Age (GA). For the fetuses of pregnant subjects, GA will be established by ultrasound, whenever possible, in combination with date of last menstrual period (LMP), when available, and fundal height. Study duration is 21 months: approximately 2 months in the start-up period, 6 months enrolling subjects, and 13 months (3-7 months while pregnant and 6 months postpartum) from last subject vaccinated until she and her infant complete follow-up. The primary objectives of this study are: 1) to assess the safety and tolerability of a single 0.5 mL intramuscular injection of BOOSTRIX in pregnant women; 2) to assess the safety of a single maternal BOOSTRIX vaccination on the fetus and infant; 3) to assess the level of Pertussis Toxin (PT) antibody at birth among infants whose mothers received a single dose of BOOSTRIX or Td while pregnant.

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Immunisation; Diphtheria; Diphtheria Immunisation; Pertussis; Tetanus; Tetanus Immunisation	Biological: Tetanus and Diphtheria Toxoids Adsorbed; Biological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide	Phase 2

Detailed Description:

This is a phase II, randomized, double-blind, active-controlled study to evaluate the safety, immunogenicity, and effect on infant immune responses of a single dose of Tetanus diphtheria acellular pertussis vaccine (Tdap) in pregnant women in Mali. 200 healthy pregnant women, ages 18 through 39 years, inclusive, who meet all eligibility criteria will be randomly allocated in a 2:1 ratio to receive either Tdap (BOOSTRIX) or Tetanus diphtheria toxoid (Td) at 14 0/7 weeks through 26 6/7 weeks estimated Gestational Age (GA). For the fetuses of pregnant subjects, GA will be established by ultrasound, whenever possible, in combination with date of last menstrual period (LMP), when available, and fundal height. Study duration is 21 months: approximately 2 months in the start-up period, 6 months enrolling subjects, and 13 months (3-7 months while pregnant and 6 months postpartum) from last subject vaccinated until she and her infant complete follow-up. The primary objectives of this study are: 1) to assess the safety and tolerability of a single 0.5 mL intramuscular injection of BOOSTRIX in pregnant women; 2) to assess the safety of a single maternal BOOSTRIX vaccination on the fetus and infant; 3) to assess the level of Pertussis Toxin (PT) antibody at birth among infants whose mothers received a single dose of BOOSTRIX or Td while pregnant. The secondary objectives are: 1) to assess the antibody response to BOOSTRIX vaccine antigens in pregnant women one month after receipt of BOOSTRIX, at the time of delivery, and at 6 months after delivery; 2) to compare the antibody levels of BOOSTRIX vaccine antigens at birth (cord blood) and 6 weeks of age (before receiving any infant doses of Diphtheria, Tetanus, and whole-cell Pertussis (DTwP)) in infants whose mothers received BOOSTRIX or Td during pregnancy; 3) to assess placental antibody transfer by determining the ratio of maternal and infant BOOSTRIX -specific antibody responses at delivery; 4) to assess interference with infant antibody responses to DTwP either prior to the second dose of the primary DTwP series, at approximately 10 weeks of age (in 1/2 of subjects), or approximately one month after the third dose of the primary DTwP series, at approximately 18 weeks of age (in 1/2 of subjects), and at 6 months of age (all subjects).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase II Double-Blind Trial to Evaluate the Safety, Immunogenicity and Effect on Infant Immune Responses of a Single Dose of Tdap in Pregnant Women in Mali
• Actual Study Start Date: January 24, 2019
• Actual Primary Completion Date: July 1, 2020
• Actual Study Completion Date: July 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1; 0.5 ml single dose of Tdap (Tetanus, Diphtheria, Acellular Pertussis Vaccine), BOOSTRIX administered intramuscularly to pregnant women at 14 0/7 weeks through 26 6/7 weeks estimated Gestational Age (GA). N=133	Biological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide; A sterile isotonic suspension of tetanus and diphtheria toxoids and pertussis antigens adsorbed on Aluminum hydroxide.
Active Comparator: Group 2; 0.5 ml single dose of Td (Tetanus, Diphtheria Toxoid) administered intramuscularly to pregnant women at 14 0/7 weeks through 26 6/7 weeks estimated GA. N=67	Biological: Tetanus and Diphtheria Toxoids Adsorbed; Used for active immunization of adults and children 7 years of age and older against diphtheria and tetanus.

Outcome Measures

Primary Outcome Measures :

1. Frequency of all SAEs in infants of women receiving Tetanus Diphtheria Toxoid (Td) during pregnancy [ Time Frame: Birth Day through 6 months of age ]
2. Frequency of all SAEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
3. Frequency of all SAEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
4. Frequency of all serious adverse events (SAEs) in infants of women receiving Tetanus Diphtheria Acellular Pertussis Vaccine (BOOSTRIX) during pregnancy [ Time Frame: Birth Day through 6 months of age ]
5. Frequency of all unsolicited non-serious adverse events (AEs) in pregnant women receiving BOOSTRIX [ Time Frame: Day 1 through Day 31 ]
6. Frequency of all unsolicited non-serious AEs in pregnant women receiving Td [ Time Frame: Day 1 through Day 31 ]
7. Frequency of pregnancy-specific AEs in infants born to women vaccinated with BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
8. Frequency of pregnancy-specific AEs in infants born to women vaccinated with Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
9. Frequency of pregnancy-specific AEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
10. Frequency of pregnancy-specific AEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
11. Frequency of solicited injection site reactogenicity events in pregnant women [ Time Frame: Day 1 through Day 8 ]
12. Frequency of solicited systemic reactogenicity events in pregnant women [ Time Frame: Day 1 through Day 8 ]
13. Frequency of study vaccine-related SAEs in infants of women receiving BOOSTRIX during pregnancy [ Time Frame: Birth Day through 6 months of age ]
14. Frequency of study vaccine-related SAEs in infants of women receiving Td during pregnancy [ Time Frame: Birth Day through 6 months of age ]
15. Frequency of study vaccine-related SAEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
16. Frequency of study vaccine-related SAEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
17. Geometric Mean Concentration (GMC) of serum IgG antibodies to Pertussis Toxin (PT), measured by Enzyme-Linked Immunosorbent Assay (ELISA) among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
18. Geometric Mean Concentration (GMC) of serum IgG antibodies to PT, measured by Enzyme-Linked Immunosorbent Assay (ELISA) among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
19. Severity of all SAEs in infants of women receiving BOOSTRIX during pregnancy [ Time Frame: Birth Day through 6 months of age ]
20. Severity of all SAEs in infants of women receiving Td during pregnancy [ Time Frame: Birth Day through 6 months of age ]
21. Severity of all SAEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
22. Severity of all SAEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
23. Severity of all unsolicited non-serious AEs in pregnant women receiving BOOSTRIX [ Time Frame: Day 1 through Day 31 ]
24. Severity of all unsolicited non-serious AEs in pregnant women receiving Td [ Time Frame: Day 1 through Day 31 ]
25. Severity of pregnancy-specific AEs in infants born to women vaccinated with BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
26. Severity of pregnancy-specific AEs in infants born to women vaccinated with Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
27. Severity of pregnancy-specific AEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
28. Severity of pregnancy-specific AEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]
29. Severity of solicited injection site reactogenicity events in pregnant women [ Time Frame: Day 1 through Day 8 ]
30. Severity of solicited systemic reactogenicity events in pregnant women [ Time Frame: Day 1 through Day 8 ]
31. Severity of study vaccine-related SAEs in infants of women receiving BOOSTRIX during pregnancy [ Time Frame: Birth Day through 6 months of age ]
32. Severity of study vaccine-related SAEs in infants of women receiving Td During pregnancy [ Time Frame: Birth day through 6 months of age ]
33. Severity of study vaccine-related SAEs in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 1 through Day 180 post-partum ]
34. Severity of study vaccine-related SAEs in pregnant women receiving Td [ Time Frame: Study Day 1 through Day 180 post-partum ]

Secondary Outcome Measures :

1. GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
2. GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
3. GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
4. GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
5. GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
6. GMC of antibodies to DTwP vaccine FHA antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
7. GMC of antibodies to DTwP vaccine FHA antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
8. GMC of antibodies to DTwP vaccine FHA antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
9. GMC of antibodies to DTwP vaccine FHA antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
10. GMC of antibodies to DTwP vaccine FHA antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
11. GMC of antibodies to DTwP vaccine Filamentous Hemagglutinin (FHA) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
12. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
13. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
14. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
15. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
16. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
17. GMC of antibodies to DTwP vaccine Fimbriae 2 (FIM2) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
18. GMC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
19. GMC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
20. GMC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
21. GMC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
22. GMC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
23. GMC of antibodies to DTwP vaccine Pertactin (PRN) antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
24. GMC of antibodies to DTwP vaccine PRN antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
25. GMC of antibodies to DTwP vaccine PRN antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
26. GMC of antibodies to DTwP vaccine PRN antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
27. GMC of antibodies to DTwP vaccine PRN antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
28. GMC of antibodies to DTwP vaccine PRN antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
29. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
30. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
31. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
32. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartumTd [ Time Frame: 10 weeks of age ]
33. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartumTd [ Time Frame: 18 weeks of age ]
34. GMC of antibodies to DTwP vaccine PT antigens, measured by ELISA among infants whose mothers received intrapartumTd [ Time Frame: 6 months of age ]
35. GMC of antibodies to DTwP vaccine tetanus antigens as measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 18 weeks of age ]
36. GMC of antibodies to DTwP vaccine tetanus antigens as measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 6 months of age ]
37. GMC of antibodies to DTwP vaccine tetanus antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
38. GMC of antibodies to DTwP vaccine tetanus antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
39. GMC of antibodies to DTwP vaccine tetanus antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 18 weeks of age ]
40. GMC of antibodies to DTwP vaccine tetanus antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 6 months of age ]
41. GMC of antibodies to whole-cell Pertussis Vaccine (DTwP) vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX [ Time Frame: 10 weeks of age ]
42. Infant GMC of serum IgG antibodies to Tdap vaccine diphtheria antigens, measured by ELISA among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
43. Infant GMC of serum IgG antibodies to Tdap vaccine diphtheria antigens, measured by ELISA among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
44. Infant GMC of serum IgG antibodies to Tdap vaccine diphtheria antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with BOOSTRIX [ Time Frame: Up to 6 weeks of age ]
45. Infant GMC of serum IgG antibodies to Tdap vaccine diphtheria antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with Td [ Time Frame: Up to 6 weeks of age ]
46. Infant GMC of serum IgG antibodies to Tdap vaccine FHA antigens, measured by ELISA among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
47. Infant GMC of serum IgG antibodies to Tdap vaccine FHA antigens, measured by ELISA among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
48. Infant GMC of serum IgG antibodies to Tdap vaccine FHA antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with BOOSTRIX [ Time Frame: Up to 6 weeks of age ]
49. Infant GMC of serum IgG antibodies to Tdap vaccine FHA antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with Td [ Time Frame: Up to 6 weeks of age ]
50. Infant GMC of serum IgG antibodies to Tdap vaccine PRN antigens as measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with BOOSTRIX [ Time Frame: Up to 6 weeks of age ]
51. Infant GMC of serum IgG antibodies to Tdap vaccine PRN antigens, measured by ELISA among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
52. Infant GMC of serum IgG antibodies to Tdap vaccine PRN antigens, measured by ELISA among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
53. Infant GMC of serum IgG antibodies to Tdap vaccine PRN antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with Td [ Time Frame: Up to 6 weeks of age ]
54. Infant GMC of serum IgG antibodies to Tdap vaccine PT antigens as measured by ELISA among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
55. Infant GMC of serum IgG antibodies to Tdap vaccine PT antigens as measured by ELISA prior to receipt of first Diphtheria, Tetanus, and whole-cell Pertussis Vaccine (DTwP) among infants born to women vaccinated with BOOSTRIX [ Time Frame: Up to 6 weeks of age ]
56. Infant GMC of serum IgG antibodies to Tdap vaccine PT antigens, measured by ELISA among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
57. Infant GMC of serum IgG antibodies to Tdap vaccine PT antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with Td [ Time Frame: Up to 6 weeks of age ]
58. Infant GMC of serum IgG antibodies to Tdap vaccine tetanus antigens, measured by ELISA among infants born to women vaccinated with BOOSTRIX [ Time Frame: Birth Day ]
59. Infant GMC of serum IgG antibodies to Tdap vaccine tetanus antigens, measured by ELISA among infants born to women vaccinated with Td [ Time Frame: Birth Day ]
60. Infant GMC of serum IgG antibodies to Tdap vaccine tetanus antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with BOOSTRIX [ Time Frame: Up to 6 weeks of age ]
61. Infant GMC of serum IgG antibodies to Tdap vaccine tetanus antigens, measured by ELISA prior to receipt of first DTwP vaccine among infants born to women vaccinated with Td [ Time Frame: Up to 6 weeks of age ]
62. Maternal Geometric Mean Concentration (GMC) of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 31 ]
63. Maternal Geometric Mean Concentration (GMC) of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Day 180 post-delivery ]
64. Maternal Geometric Mean Concentration (GMC) of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Delivery Day ]
65. Maternal Geometric Mean Concentration (GMC) of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Study Day 31 ]
66. Maternal GMC of serum IgG antibodies to diphtheria antigen of vaccine measured by ELISA in pregnant women receiving Td [ Time Frame: Day 180 post-delivery ]
67. Maternal GMC of serum IgG antibodies to diphtheria antigen of vaccine measured by ELISA in pregnant women receiving Td [ Time Frame: Delivery Day ]
68. Maternal GMC of serum IgG antibodies to diphtheria antigen of vaccine measured by ELISA in pregnant women receiving Td [ Time Frame: Study Day 31 ]
69. Maternal GMC of serum IgG antibodies to Tdap FHA antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Delivery Day ]
70. Maternal GMC of serum IgG antibodies to Tdap vaccine diphtheria antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Day 180 post-delivery ]
71. Maternal GMC of serum IgG antibodies to Tdap vaccine diphtheria antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Delivery Day ]
72. Maternal GMC of serum IgG antibodies to Tdap vaccine diphtheria antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 31 ]
73. Maternal GMC of serum IgG antibodies to Tdap vaccine FHA antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Day 180 post-delivery ]
74. Maternal GMC of serum IgG antibodies to Tdap vaccine FHA antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 31 ]
75. Maternal GMC of serum IgG antibodies to Tdap vaccine FHA antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Day 180 post-delivery ]
76. Maternal GMC of serum IgG antibodies to Tdap vaccine FHA antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Delivery Day ]
77. Maternal GMC of serum IgG antibodies to Tdap vaccine FHA antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Study Day 31 ]
78. Maternal GMC of serum IgG antibodies to Tdap vaccine PRN antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 31 ]
79. Maternal GMC of serum IgG antibodies to Tdap vaccine PRN antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Day 180 post-delivery ]
80. Maternal GMC of serum IgG antibodies to Tdap vaccine PRN antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Delivery Day ]
81. Maternal GMC of serum IgG antibodies to Tdap vaccine PRN antigen, measured by ELISA in pregnant women receiving Td [ Time Frame: Study Day 31 ]
82. Maternal GMC of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Day 180 post-delivery ]
83. Maternal GMC of serum IgG antibodies to Tdap vaccine PT antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Delivery Day ]
84. Maternal GMC of serum IgG antibodies to Tdap vaccine tetanus antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Day 180 post-delivery ]
85. Maternal GMC of serum IgG antibodies to Tdap vaccine tetanus antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Delivery Day ]
86. Maternal GMC of serum IgG antibodies to Tdap vaccine tetanus antigen, measured by ELISA in pregnant women receiving BOOSTRIX [ Time Frame: Study Day 31 ]
87. Maternal GMC of serum IgG antibodies to tetanus antigen of vaccine, measured by ELISA in pregnant women receiving Td [ Time Frame: Day 180 post-delivery ]
88. Maternal GMC of serum IgG antibodies to tetanus antigen of vaccine, measured by ELISA in pregnant women receiving Td [ Time Frame: Delivery Day ]
89. Maternal GMC of serum IgG antibodies to tetanus antigen of vaccine, measured by ELISA in pregnant women receiving Td [ Time Frame: Study Day 31 ]
90. MC of antibodies to DTwP vaccine Fimbriae 3 (FIM3) antigens, measured by ELISA among infants whose mothers received intrapartum Td [ Time Frame: 10 weeks of age ]
91. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific diphtheria antibodies, measured by ELISA after intrapartum receipt of BOOSTRIX [ Time Frame: Delivery Day ]
92. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific diphtheria antibodies, measured by ELISA after intrapartum receipt of Td [ Time Frame: Delivery Day ]
93. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific FHA antibodies, measured by ELISA after intrapartum receipt of BOOSTRIX [ Time Frame: Delivery Day ]
94. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific FHA antibodies, measured by ELISA after intrapartum receipt of Td [ Time Frame: Delivery Day ]
95. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific PRN antibodies, measured by ELISA after intrapartum receipt of BOOSTRIX [ Time Frame: Delivery Day ]
96. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific PRN antibodies, measured by ELISA after intrapartum receipt of Td [ Time Frame: Delivery Day ]
97. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific PT antibodies, measured by ELISA after intrapartum receipt of BOOSTRIX [ Time Frame: Delivery Day ]
98. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific PT antibodies, measured by ELISA after intrapartum receipt of Td [ Time Frame: Delivery Day ]
99. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific tetanus antibodies, measured by ELISA after intrapartum receipt of BOOSTRIX [ Time Frame: Delivery Day ]
100. Placental geometric mean ratio (GMR) of maternal and infant-specific Tdap-specific tetanus antibodies, measured by ELISA after intrapartum receipt of Td. [ Time Frame: Delivery Day ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 39 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy pregnant woman 18-39 years of age, inclusive.
2. Singleton fetus, with estimated gestational age of 14 0/7 through 26 6/7 weeks gestation, inclusive, on the day of study vaccination.

3. Provide written consent after the nature of the study has been explained according to local regulatory requirements and prior to any study procedures*.

   *Prior to obtaining individual informed consent for each subject, the investigators will obtain community consent by discussing the trial with all the appropriate local groups, as necessary, to obtain permission to approach the subjects. Written, informed consent for participation in the trial will be obtained by the investigators from all individual subjects. The consent forms will be written in French, the official language of Mali, and will be translated into Bambara, the most prevalent of the local languages, and recorded on audiotape.

4. In good health as determined by medical history, targeted physical examination* (physical examination performed as part of routine antenatal care of a study-specific brief exam may be used to determine eligibility), vital signs (oral temperature < 37.8 degrees Celsius; pulse 55 to 100 beats per minute (bpm), inclusive; systolic blood pressure 90 to 140 millimeters of mercury (mm Hg), inclusive; diastolic blood pressure 55 to 90 mm Hg, inclusive), and clinical judgment of the investigator.

   *If indicated based on medical history, to evaluate acute or currently ongoing chronic medical diagnoses or conditions that would affect the assessment of eligibility and safety of subjects. Chronic medical diagnoses or conditions being actively managed must be within acceptable limits in the last 180 days. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and the study vaccination are acceptable provided the subject is asymptomatic, condition stable, and there is no additional risk to the subject or interference with the evaluation of responses to the study vaccination.

5. Ability to comprehend and comply with all study procedures, as determined by the investigator determining eligibility, and availability for follow-up.
6. Willing to allow study staff to gather pertinent medical information, including pregnancy outcome data and medical information about her infant.

Exclusion Criteria:

1. History of illness or an ongoing illness that, in the opinion of the investigator, may pose additional risk to the subject or her fetus if she participates in the study.
2. Infection requiring systemic antibiotics or antiviral treatment within the 7 days prior to study vaccination.

3. Fever (oral temperature > / = 37.8 degrees Celsius/100.0 degrees Fahrenheit) or other acute illness within 3 days prior to study vaccination*.

   *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

4. Known active neoplastic disease (excluding non-melanoma skin cancer), anticancer chemotherapy, or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
5. History of any hematologic malignancy at any time.
6. A history of a serious adverse event following previous immunizations (e.g., Bell's Palsy, Guillain-Barre Syndrome, encephalopathy), or history of progressive neurologic disorders.
7. Known or suspected disease that impairs the immune system including known or suspected HIV infection or HIV-related disease.
8. Receipt of immunosuppressive therapy, including long-term use of glucocorticoids: oral, inhaled, intranasal or parenteral prednisone > / = 20 mg/day or equivalent for more than 2 weeks within the 30 days prior to enrollment. Use of topical corticosteroids is allowed.
9. Known hepatitis B or hepatitis C infection, by history or medical record.
10. Behavioral or cognitive impairment or psychiatric disease (includes hospitalization for psychiatric illness, suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination) that, in the opinion of the investigator, may interfere with the subject's ability to participate in the trial.
11. Have a history of alcohol or drug abuse within 5 years prior to study vaccination (that is believed by the site investigator to potentially interfere with the subject's ability to participate in the study).
12. Known hypersensitivity or allergy to any component of the study vaccine (formaldehyde, alum).
13. History of severe allergic reaction (e.g., anaphylaxis) after a previous dose of BOOSTRIX or any other vaccine directed against tetanus, diphtheria, or pertussis.
14. Receipt or planned receipt of any live licensed vaccine within 30 days before or after vaccination or any inactivated licensed vaccine within 14 days before or after vaccination.
15. Receipt of immunoglobulin (except RhoGAM, which is allowed) or other blood products within 90 days prior to study vaccination.

16. Receipt of an experimental agent or device within 30 days prior to vaccination, or the expected receipt of an experimental agent* (other than BOOSTRIX) during this trial-reporting period.

    *Experimental agents include vaccines, drugs, biologics, devices, blood products, and medications. Subjects who have received a licensed product, as a subject in a clinical trial, within 30 days prior to vaccination or who are expecting to enroll in such a trial during the study period will also be excluded. Observational studies, surveys, and other studies that do not involve experimental agents or devices are allowed.

17. High risk for serious obstetrical complication (refer to ACOG Practice Bulletins for definitions, as necessary)*.

    *Including the following: (a) gestational hypertension (well controlled history of essential or gestational hypertension, as evidenced by normal BPs as defined above, is allowed), (b) gestational diabetes not controlled by diet and exercise (the use of insulin or glyburide to control gDM, at the time of enrollment, is exclusionary), (c) current pre-eclampsia or eclampsia, (d) known current multiple gestation, (e)history of preterm delivery before EGA 35 weeks 0 days or current preterm labor, and/or (f) known intrauterine fetal growth restriction (defined as ultrasound confirmation of an estimated fetal weight that is less than the 10th percentile for gestational age).

18. Pregnant with a fetus with a known or suspected major congenital anomaly or genetic abnormality.
19. Study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.

Contacts and Locations

Locations

Mali

Center for Vaccine Development - Mali

Bamako, Mali

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Informed Consent Form  [PDF] September 24, 2018

More Information

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03589768
• Other Study ID Numbers: 16-0024; HHSN272201300022I
• First Posted: July 18, 2018
• Last Update Posted: June 24, 2021
• Last Verified: October 4, 2018

• 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.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

BOOSTRIX; Immunogenicity; Infant; Mali; Phase II; Pregnant Women; Safety; Tdap

Additional relevant MeSH terms:

Tetanus; Diphtheria; Tetany; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Clostridium Infections; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Hypocalcemia; Calcium Metabolism Disorders; Metabolic Diseases; Corynebacterium Infections; Actinomycetales Infections; Aluminum Hydroxide; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents