Study on the Safety and Immunogenicity of Boostrix Vaccine in Pregnant Malian Women and Their Infants
Condition: Clostridium Difficile Immunisation; Diphtheria; Diphtheria Immunisation; Pertussis; Tetanus; Tetanus Immunisation
MeSH terms: Tetanus; Diphtheria; Tetany
Intervention: Tetanus and Diphtheria Toxoids Adsorbed; Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed onto aluminum hydroxide
Intervention description: Used for active immunization of adults and children 7 years of age and older against diphtheria and tetanus.; A sterile isotonic suspension of tetanus and diphtheria toxoids and pertussis antigens adsorbed on Aluminum hydroxide.
Intervention MeSH terms: Aluminum Hydroxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 399.0
Sex: Female
Minimum age: 18 Years
Maximum age: 39 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: BOOSTRIX; Immunogenicity; Infant; Mali; Phase II; Pregnant Women; Safety; Tdap

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.
    

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.