Brief Title
Study on the Safety and Immunogenicity of Boostrix Vaccine in Pregnant Malian Women and Their Infants
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
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.
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Frequency of all SAEs in infants of women receiving Tetanus Diphtheria Toxoid (Td) during pregnancy
Secondary Outcome
GMC of antibodies to DTwP vaccine diphtheria antigens, measured by ELISA among infants whose mothers received intrapartum BOOSTRIX
Condition
Clostridium Difficile Immunisation
Intervention
Tetanus and Diphtheria Toxoids Adsorbed
Study Arms / Comparison Groups
Group 1
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
399
Start Date
January 24, 2019
Completion Date
July 1, 2020
Primary Completion Date
July 1, 2020
Eligibility 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.
Gender
Female
Ages
18 Years - 39 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
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Location Countries
Mali
Location Countries
Mali
Administrative Informations
NCT ID
NCT03589768
Organization ID
16-0024
Secondary IDs
HHSN272201300022I
Responsible Party
Sponsor
Study Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor
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Verification Date
October 4, 2018