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

NCT03589768 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 16-0024
• Study Type: interventional
• Target: 399
• Locations: 2 countries
• Sites: 2

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.

Conditions

Clostridium Difficile Immunisation; Diphtheria; Diphtheria Immunisation; Pertussis; Tetanus; Tetanus Immunisation

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Number of Pregnant Women Reporting Related Serious Adverse Events (SAEs) and Unrelated SAEs

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All SAEs were reported from time of first study vaccination through approximately 6 months after the first study vaccination

  Study Day 1 through Day 180 (6-months post-partum)

• Number of Pregnant Women Reporting Pregnancy-Specific Adverse Events (AEs)

  Pregnancy related AEs include: pregnancy loss (graded as severe \[grade 3\] if occurred), bleeding during pregnancy prior to the onset of labor, postpartum hemorrhage, postabortal endometritis/salpingitis, preterm rupture of membranes, preterm contractions/labor/delivery, poor fetal growth, hypertension, preeclampsia/eclampsia, chorioamnionitis, postpartum endometriosis, gestational diabetes mellitus, and/or pregnancy-related clinical AE not previously identified in this list.

  Study Day 1 through Day 180 (6-months post-partum)

• Number of Infants Reporting Related SAEs and Unrelated SAEs

  SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All SAEs were reported from time of birth through 6 months of age.

  Birth Day through 6 months of age

• Number of Infants Reporting Pregnancy-specific AEs

  Infant pregnant related AEs include: preterm birth, low birth weight, neonatal complications in a term infant, congenital anomalies/birth defects, and/or clinical AE in the newborn not identified previously in this list.

  Birth Day through 6 months of age

• Number of Pregnant Women Reporting Solicited Injection Site and Systemic Reactogenicity Events

  Local AEs solicited on a memory aid provided to participants included Pain, Tenderness, Ecchymosis (functional grade based on interference with daily activities), Ecchymosis (any measured value \>0mm), Erythema (functional grade), Erythema (any measured value \>0mm), Induration (functional grade), and Induration (any measured value \>0mm). Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, Allergic reaction, and Nausea. Participants are considered reporting the local or systemic AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.

  Pre-Dose Day 1, Post-Dose Day 1, Day 4, Day 8

• Number of Pregnant Women Reporting Unsolicited Non-serious AEs

  Frequency of all unsolicited non-serious AEs from day of study vaccination (Day 1) to Day 31, compared between those who received BOOSTRIX and those who received Td.

  Day 1 through Day 31

• Geometric Mean Concentration (GMC) of Serum IgG Antibodies to Pertussis Toxin (PT) in Infants Born to Women Receiving BOOSTRIX or Td

  Geometric Mean Concentration (GMC) of serum IgG antibodies to PT as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td. DTwP is Diphtheria, Tetanus, and whole cell Pertussis vaccine.

  Birth Day, Prior to receipt of first dose of DTwP (approximately 6 weeks of age), One month after receipt of first dose of DTwP (approximately 10 weeks of age), One month after receipt of last dose of DTwP (approximately 18 weeks of age), 6 months of age

Secondary Outcomes (11)

• GMC of Serum IgG Antibodies to PT in Pregnant Women Receiving BOOSTRIX or Td

  Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)

• GMC of Serum IgG Antibodies to Filamentous Hemagglutinin (FHA) in Pregnant Women Receiving BOOSTRIX or Td

  Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)

• GMC of Serum IgG Antibodies to Pertactin (PRN) in Pregnant Women Receiving BOOSTRIX or Td

  Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)

• GMC of Serum IgG Antibodies to Tetanus in Pregnant Women Receiving BOOSTRIX or Td

  Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)

• GMC of Serum IgG Antibodies to Diphtheria in Pregnant Women Receiving BOOSTRIX or Td

  Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)

Study Arms (2)

Group 1

EXPERIMENTAL

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

Group 2

ACTIVE COMPARATOR

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

Interventions

Tetanus and Diphtheria Toxoids Adsorbed BIOLOGICAL

Used for active immunization of adults and children 7 years of age and older against diphtheria and tetanus.

Group 2

Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide BIOLOGICAL

A sterile isotonic suspension of tetanus and diphtheria toxoids and pertussis antigens adsorbed on Aluminum hydroxide.

Group 1

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy pregnant woman 18-39 years of age, inclusive.
• Singleton fetus, with estimated gestational age of 14 0/7 through 26 6/7 weeks gestation, inclusive, on the day of study vaccination.
• 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.
• 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.
• Ability to comprehend and comply with all study procedures, as determined by the investigator determining eligibility, and availability for follow-up.
• Willing to allow study staff to gather pertinent medical information, including pregnancy outcome data and medical information about her infant.

You may not qualify if:

• 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.
• Infection requiring systemic antibiotics or antiviral treatment within the 7 days prior to study vaccination.
• 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.
• Known active neoplastic disease (excluding non-melanoma skin cancer), anticancer chemotherapy, or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
• History of any hematologic malignancy at any time.
• 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.
• Known or suspected disease that impairs the immune system including known or suspected HIV infection or HIV-related disease.
• 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.
• Known hepatitis B or hepatitis C infection, by history or medical record.
• 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.
• 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).
• Known hypersensitivity or allergy to any component of the study vaccine (formaldehyde, alum).
• History of severe allergic reaction (e.g., anaphylaxis) after a previous dose of BOOSTRIX or any other vaccine directed against tetanus, diphtheria, or pertussis.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

University of Maryland, School of Medicine, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201-1509, United States

Location

Center for Vaccine Development - Mali

Bamako, Mali

Location

Related Publications (1)

• Haidara FC, Tapia MD, Diallo F, Portillo S, Williams M, Traore A, Rotrosen E, Hensel E, Makowski M, Selamawi S, Powell JA, Kotloff KL, Pasetti MF, Sow SO, Neuzil KM. Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study. EClinicalMedicine. 2024 Mar 28;71:102556. doi: 10.1016/j.eclinm.2024.102556. eCollection 2024 May.

  PMID: 38586589 DERIVED

MeSH Terms

Conditions

Diphtheria; Whooping Cough; Tetanus

Interventions

Tetanus Toxoid

Condition Hierarchy (Ancestors)

Corynebacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Bordetella Infections; Gram-Negative Bacterial Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Clostridium Infections

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Kathleen M. Neuzil, MD, MPH
• Organization: University of Maryland School of Medicine

kneuzil@medicine.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 18, 2018
• Study Start: January 24, 2019
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: May 21, 2025
• Results First Posted: January 20, 2023

Record last verified: 2018-10-04

Locations

US (1); MA (1)