Clostridium Difficile ImmunisationPhase 2NCT03589768
Study on the Safety and Immunogenicity of Boostrix Vaccine in Pregnant Malian Women and Their Infants
A Phase 2 study testing Tetanus and Diphtheria Toxoids Adsorbed and Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide in people with Clostridium Difficile Immunisation and Diphtheria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 39 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Clostridium Difficile Immunisation, Diphtheria, Diphtheria Immunisation
- What is being tested?
- Tetanus and Diphtheria Toxoids Adsorbed and Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 399 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 24 Jan 2019to 1 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- 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.
- 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.
Who cannot join
- 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.
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- 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.
- Receipt of immunoglobulin (except RhoGAM, which is allowed) or other blood products within 90 days prior to study vaccination.
- 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.
- 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).
- Pregnant with a fetus with a known or suspected major congenital anomaly or genetic abnormality.
- Study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, 21201-1509
About this study
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
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.
Read the 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).
- Conditions
- Clostridium Difficile Immunisation, Diphtheria, Diphtheria Immunisation, Pertussis, Tetanus, Tetanus Immunisation
- Being tested
- Tetanus and Diphtheria Toxoids Adsorbed, Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide
- Keywords
- BOOSTRIX, Immunogenicity, Infant, Mali, Phase II, Pregnant Women, Safety, Tdap
- Medical subject headings
- Diphtheria, Whooping Cough, Tetanus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetanus and Diphtheria Toxoids AdsorbedBiological
Used for active immunization of adults and children 7 years of age and older against diphtheria and tetanus.
Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxideBiological
A sterile isotonic suspension of tetanus and diphtheria toxoids and pertussis antigens adsorbed on Aluminum hydroxide.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Biological: Tetanus and Diphtheria Toxoids Adsorbed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
GMC of serum IgG antibodies to PT as measured by Enzyme-Linked Immunosorbent Assay (ELISA) between women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of serum IgG antibodies to FHA as measured by Enzyme-Linked Immunosorbent Assay (ELISA) between women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of serum IgG antibodies to PRN as measured by Enzyme-Linked Immunosorbent Assay (ELISA) between women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of serum IgG antibodies to Tetanus as measured by Enzyme-Linked Immunosorbent Assay (ELISA) between women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of serum IgG antibodies to Diphtheria as measured by Enzyme-Linked Immunosorbent Assay (ELISA) between women vaccinated with BOOSTRIX or Td.
Measured: Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)
GMC of Serum IgG Antibodies to FHA in Infants Born to Women Receiving BOOSTRIX or Td
GMC of serum IgG antibodies to FHA as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of Serum IgG Antibodies to PRN in Infants Born to Women Receiving BOOSTRIX or Td
GMC of serum IgG antibodies to PRN as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of Serum IgG Antibodies to Tetanus in Infants Born to Women Receiving BOOSTRIX or Td
GMC of serum IgG antibodies to Tetanus as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of Serum IgG Antibodies to Diphtheria in Infants Born to Women Receiving BOOSTRIX or Td
GMC of serum IgG antibodies to Diphtheria as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td.
Measured: 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
GMC of Serum IgG Antibodies to Fimbriae 2/3 (FIM 2/3) in Infants Born to Women Receiving BOOSTRIX or Td
GMC of serum IgG antibodies to FIM 2/3 as measured by Enzyme-Linked Immunosorbent Assay (ELISA) at birth between infants born to women vaccinated with BOOSTRIX or Td.
Measured: 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
Geometric Mean Ratio (GMR) of Maternal and Infant-specific Tdap-specific Antibodies
GMR of maternal and infant-specific Tdap-specific antibodies (PT, FHA, PRN, tetanus, diphtheria) as measured by ELISA at delivery/birth after intrapartum receipt of BOOSTRIX versus Td. GMR represents the geometric mean ratio in infant antibody concentration at birth to maternal antibody concentration at delivery.
Measured: Time of delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2018
- Study start24 Jan 2019
- Primary completion1 Jul 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile ImmunisationStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 399 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03589768
- Sponsor's protocol ID
- 16-0024
- Status last verified
- 4 Oct 2018
- First submitted
- 14 Jun 2018
- Last updated
- 21 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38586589
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03589768
- Acronym / sponsor ID
- 16-0024
- Conditions
- Clostridium Difficile Immunisation, Diphtheria, Diphtheria Immunisation, Pertussis, Tetanus, Tetanus Immunisation
- Keywords
- BOOSTRIX, Immunogenicity, Infant, Mali, Phase II, Pregnant Women, Safety, Tdap
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 399 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 24 Jan 2019 (actual)
- Primary completion
- 1 Jul 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 18 Jul 2018 (actual)
- Results
- Posted 20 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide0.5 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 |
| Group 2 | Active comparator | Biological: Tetanus and Diphtheria Toxoids Adsorbed0.5 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 |
Who may qualify
- Ages
- 18 to 39 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tetanus and Diphtheria Toxoids AdsorbedUsed for active immunization of adults and children 7 years of age and older against diphtheria and tetanus. | Biological | Group 2 |
| Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxideA sterile isotonic suspension of tetanus and diphtheria toxoids and pertussis antigens adsorbed on Aluminum hydroxide. | Biological | Group 1 |
Primary outcome
Number of Pregnant Women Reporting Related Serious Adverse Events (SAEs) and Unrelated SAEs
Time frame: Study Day 1 through Day 180 (6-months post-partum)
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
Number of Pregnant Women Reporting Pregnancy-Specific Adverse Events (AEs)
Time frame: Study Day 1 through Day 180 (6-months post-partum)
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.
Number of Infants Reporting Related SAEs and Unrelated SAEs
Time frame: Birth Day through 6 months of age
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.
Number of Infants Reporting Pregnancy-specific AEs
Time frame: Birth Day through 6 months of age
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.
Number of Pregnant Women Reporting Solicited Injection Site and Systemic Reactogenicity Events
Time frame: Pre-Dose Day 1, Post-Dose Day 1, Day 4, Day 8
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.
Number of Pregnant Women Reporting Unsolicited Non-serious AEs
Time frame: Day 1 through Day 31
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.
Geometric Mean Concentration (GMC) of Serum IgG Antibodies to Pertussis Toxin (PT) in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
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.
11 secondary outcomes
GMC of Serum IgG Antibodies to PT in Pregnant Women Receiving BOOSTRIX or Td
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Pre-dose Day 1, One month after vaccination, at delivery, Day 180 (approximately 6 months after delivery)
GMC of Serum IgG Antibodies to FHA in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
GMC of Serum IgG Antibodies to PRN in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
GMC of Serum IgG Antibodies to Tetanus in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
GMC of Serum IgG Antibodies to Diphtheria in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
GMC of Serum IgG Antibodies to Fimbriae 2/3 (FIM 2/3) in Infants Born to Women Receiving BOOSTRIX or Td
Time frame: 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
Geometric Mean Ratio (GMR) of Maternal and Infant-specific Tdap-specific Antibodies
Time frame: Time of delivery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38586589Haidara 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tetanus and Diphtheria Toxoids Adsorbed and Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide in people with Clostridium Difficile Immunisation and Diphtheria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Mali. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Pregnant Women Reporting Related Serious Adverse Events (SAEs) and Unrelated SAEs (time frame: Study Day 1 through Day 180 (6-months post-partum)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03589768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.