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Safety and Dose Ranging Study of Acellular Pertussis and Acellular Pertussis -Tetanus-Diphtheria Booster Vaccines in Healthy Adults Ages 18 to 40 Years

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT01529645
First received: February 6, 2012
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

This study will evaluate the safety and efficacy of 9 different vaccines containing aP (acellular pertussis) and TdaP (acellular pertussis, tetanus and diphtheria) in healthy subjects 18 to 40 years of age.


Condition Intervention Phase
Pertussis
Whooping Cough
Tetanus
Lockjaw
Diphtheria
Biological: Acellular pertussis vaccine
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Biological: Licensed TdaP booster vaccine
Biological: Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)
Other: Saline solution
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Phase I, Randomized, Controlled, Observer-Blind, Dose-Ranging Study of Acellular Pertussis and Tetanus-Diptheria-Acellular Pertussis Booster Vaccine in Adults Ages 18 to 40 Years.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine [ Time Frame: Day 1 through 7 after vaccination ] [ Designated as safety issue: Yes ]
    The safety profiles of different antigenic formulations of the aP and TdaP booster vaccines were assessed and compared to that of licensed comparator in terms of the number of subjects reporting solicited local and systemic adverse events and other adverse events after vaccination.

  • The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine [ Time Frame: From day 1 to day 365 ] [ Designated as safety issue: Yes ]
    The safety profiles of different antigenic formulations of the aP and TdaP booster vaccines were assessed in terms of the number of subjects reporting any unsolicited adverse events (AEs) between day 1 to day 30 , serious adverse events (SAEs) and AEs leading to premature withdrawal between day 1 to day 365, after vaccination.

  • Geometric Mean Concentrations (GMCs) of Antibodies in aP1, aP2, aP4 Groups Against Pertussis Antigens Following Booster Vaccination [ Time Frame: Day 1 (baseline) and Day 30 post vaccination ] [ Designated as safety issue: No ]
    The GMCs of antibodies as measured by enzyme-linked immunosorbent assay (ELISA) on aP booster groups, against pertussis antigens pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), following vaccination with different antigenic formulations of aP versus the response to the commercially available comparator are reported.

  • GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Groups Against Pertussis Antigens Following Booster Vaccination [ Time Frame: Day 1 (baseline) and Day 30 post vaccination ] [ Designated as safety issue: No ]
    The GMCs of antibodies as measured by enzyme-linked immunosorbent assay (ELISA) in TdaP Booster Groups against pertussis antigens (PT, FHA and PRN), following vaccination with different antigenic formulations of TdaP booster versus the response to the commercially available comparator are reported.

  • GMCs of Antibodies in T5D4aP1, T5D4aP2 and T5D4aP4 Groups Against Pertussis Antigens Following Vaccination [ Time Frame: Day 1 (baseline) and Day 30 post vaccination ] [ Designated as safety issue: No ]
    The GMCs of antibodies as measured by enzyme-linked immunosorbent assay (ELISA) in TdaP booster groups, against pertussis antigens (PT, FHA and PRN), following vaccination with different antigenic formulations of TdaP booster versus the response to the commercially available comparator are reported.

  • Geometric Mean Ratios (GMRs) of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in aP1, aP2, aP4 Booster Groups Against Pertussis Antigens [ Time Frame: Day 30 post vaccination/baseline (Day 1) ] [ Designated as safety issue: No ]
    The GMRs of post-vaccination versus pre-vaccination GMCs of antibodies against pertussis antigens (PT, FHA and PRN) for different antigenic formulations of aP booster vaccines and for licensed comparator are reported.

  • GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Booster Groups Against Pertussis Antigens [ Time Frame: Day 30 post vaccination/baseline (Day 1) ] [ Designated as safety issue: No ]
    The GMRs of post-vaccination versus pre-vaccination GMCs of antibodies against pertussis antigens (PT, FHA and PRN) for TdaP booster groups and for licensed comparator are reported.

  • GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies for T5D4aP1, T5D4aP2 and T5D4aP4 Booster Groups Against Pertussis Antigens [ Time Frame: Day 30 post vaccination/baseline (Day 1) ] [ Designated as safety issue: No ]
    The GMRs of post-vaccination versus pre-vaccination GMCs of antibodies against pertussis antigens (PT, FHA and PRN) for TdaP booster groups and for licensed comparator are reported.

  • Percentages of Subjects With Diphtheria and Tetanus Antitoxin Units >= 0.1/mL After Vaccination [ Time Frame: Day 1 (baseline) and Day 30 post vaccination ] [ Designated as safety issue: No ]
    The percentages of subjects demonstrating diphtheria and tetanus antitoxin units >= 0.1/mL following vaccination with different antigenic formulations of TdaP booster vaccine, is compared to the response to commercially available comparator.


Secondary Outcome Measures:
  • Percentages of Subjects With 2- and 4-fold Increase in GMCs Against Pertussis Antigens Following Vaccination. [ Time Frame: Day 30 post vaccination ] [ Designated as safety issue: No ]
    Comparison of antibody responses against pertussis antigens (PT, FHA and PRN), following vaccination with different antigenic formulations of aP and TdaP booster vaccines and licensed comparator, are reported in terms of the percentages of subjects demonstrating 2- and 4-fold increase in GMCs from baseline.

  • GMCs of Antibodies Against Diphtheria and Tetanus Antigens Following Vaccination [ Time Frame: Day 1 (baseline) and Day 30 post vaccination ] [ Designated as safety issue: No ]
    The GMCs of antibodies against diphtheria and tetanus antigens following vaccination with different formulations of TdaP booster are compared with the response to the commercially available comparator.

  • GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies Against Diphtheria and Tetanus Antigens [ Time Frame: Day 30 post vaccination/Day 1 ] [ Designated as safety issue: No ]
    The GMRs of post vaccination versus pre vaccination GMCs of antibodies against diphtheria and tetanus antigens for different formulations of TdaP booster and commercially available comparator versus GMCs at baseline are reported.


Enrollment: 420
Study Start Date: March 2012
Study Completion Date: July 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: aP booster
Subjects received acellular pertussis (aP) vaccine with different antigen dose formulations: low dose of PT, FHA, PRN, followed by one fixed dose of diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany) administered one month apart.
Biological: Acellular pertussis vaccine
Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Biological: Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)
To ensure all subjects receive a tetanus and diphtheria booster vaccination, an injection was administered on Study Day 30, one month after the administration of the investigational vaccine.
Experimental: Group 2: aP booster
Subjects received acellular pertussis (aP) vaccine with different antigen dose formulations: medium dose of PT, FHA, PRN, followed by one fixed dose of diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany) administered one month apart.
Biological: Acellular pertussis vaccine
Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Biological: Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)
To ensure all subjects receive a tetanus and diphtheria booster vaccination, an injection was administered on Study Day 30, one month after the administration of the investigational vaccine.
Experimental: Group 3: aP booster
Subjects received acellular pertussis (aP) vaccine with different antigen dose formulations: high dose of PT, FHA, PRN, followed by one fixed dose of diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany) administered one month apart.
Biological: Acellular pertussis vaccine
Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Biological: Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)
To ensure all subjects receive a tetanus and diphtheria booster vaccination, an injection was administered on Study Day 30, one month after the administration of the investigational vaccine.
Experimental: Group 4: TdaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: low dose of PT, FHA, PRN, low dose of D (diphteria) toxoid, fixed dose of T (tetanus) toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Experimental: Group 5: TdaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: medium dose of PT, FHA, PRN, low dose of D toxoid, fixed dose of T toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Experimental: Group 6: TdaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: high dose of PT, FHA, PRN, low dose of D toxoid, fixed dose of T toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Experimental: Group 7: TdaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: low dose of PT, FHA, PRN, double dose of D toxoid, fixed dose of T toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Experimental: Group 8: TdaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: medium dose of PT, FHA, PRN, double dose of D toxoid, fixed dose of T toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Experimental: Group 9: TDaP booster
Subjects received tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed) with different antigen dose formulations: high dose of PT, FHA, PRN, double dose of D toxoid, fixed dose of T toxoid, followed by one administration of saline solution one month apart.
Biological: Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)
Tetanus, reduced diphtheria, and acellular pertussis (TdaP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.
Active Comparator: Group 10: Licensed TdaP booster
Subject received one dose of a licensed TdaP booster vaccine (containing 8 μg each of PT, FHA and 2.5 μg of PRN antigens and 2.5 Lf of diphtheria toxoid and 5 Lf of tetanus toxoid) followed by one administration of saline solution one month apart.
Biological: Licensed TdaP booster vaccine
Licenced TdaP booster vaccine was administered intramuscularly in the upper deltoid region of the subject's non-dominant arm.
Other: Saline solution
Subjects received one injection of saline solution at one month after vaccination.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy male and female individuals between 18 and 40 years of age (inclusive) who had provided informed consent.
  2. Individuals who were able to be contacted for the duration of the study.

Exclusion Criteria:

  1. Individuals who had received vaccines containing T, D, or pertussis (aP or whole cell), been diagnosed with pertussis disease, or who have had a household exposure to pertussis within the past 8 years.
  2. If female, "of childbearing potential", sexually active, and had not used any of the "acceptable contraceptive methods" for at least 2 months prior to study entry:

    1. Of childbearing potential was defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy.
    2. Acceptable birth control methods were defined as one or more of the following:

      • Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring);
      • Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse;
      • Intrauterine device (IUD);
      • Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the subject's study entry.
  3. If female of childbearing potential and sexually active, refusal to use an "acceptable contraceptive method" through to 3 weeks after last study vaccination.
  4. Any positive or indeterminate pregnancy test.
  5. Female individuals who were pregnant or breastfeeding.
  6. Individuals with contraindications, warnings and/or precautions to vaccination with Boostrix or Td-pur as specified within the summary of product characteristics.
  7. Individuals with a clinically significant active infection (as assessed by the investigator) or oral body temperature ≥38°C/100.4ºF within 3 days of the intended date of vaccination.
  8. Known hypersensitivity or allergy to diphtheria, tetanus, or pertussis vaccine (including excipients of the investigational study vaccines, control or placebo as summarized in protocol section 5.0).
  9. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, might have interfered with the subject's ability to participate in the study.
  10. Individuals with any progressive or severe neurologic disorder, seizure disorder or Guillian-Barré syndrome.
  11. Individuals with history or any illness that, in the opinion of the investigator, might have interfered with the results of the study or pose additional risk to the individuals due to participation in the study.
  12. Known or suspected impairment/alteration of immune function, including:

    1. chronic use of oral steroids (≥15 days of use) within 60 days prior to visit 1 (day 1) (use of inhaled, intranasal, or topical corticosteroids was allowed);
    2. receipt of parenteral steroids within 60 days prior to visit 1 (day 1);
    3. receipt of immunostimulants within 60 days prior to visit 1 (day 1);
    4. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to visit 1 (day 1) or planned during the full length of the study;
    5. HIV infection or HIV-related disease;
    6. Heritable immunodeficiency.
  13. Abnormalities of splenic or thymic function.
  14. Individuals with a known bleeding diathesis, or any condition that might have been associated with a prolonged bleeding time.
  15. Individuals with any serious chronic or progressive disease according to judgment of the investigator (neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
  16. Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (= weight in kg / (height in meters x height in meters)).
  17. Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or with intent to participate in another clinical study at any time during the conduct of this study.
  18. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who were planning to receive any vaccine other than Td or placebo within 28 days from the study vaccines.
  19. Individuals who were first degree relatives of subjects involved in trial conduct.
  20. Individuals with history of substance or alcohol abuse within the past 2 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01529645

Locations
Belgium
Center for Vaccinology (CEVAC), Ghent University Hospital
De Pintelaan, B-9000 Ghent, Belgium, 185
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
Principal Investigator: Geert Leroux-Roels, Prof. Dr. Center for Vaccinology (CEVAC), Ghent University Hospital
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01529645     History of Changes
Other Study ID Numbers: V113_01, 2011-000688-28
Study First Received: February 6, 2012
Results First Received: April 30, 2014
Last Updated: September 16, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Novartis:
pertussis
booster vaccine
tetanus
diphtheria in adults

Additional relevant MeSH terms:
Whooping Cough
Tetanus
Tetany
Diphtheria
Bordetella Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Respiratory Tract Infections
Infection
Respiratory Tract Diseases
Clostridium Infections
Gram-Positive Bacterial Infections
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Hypocalcemia
Calcium Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Corynebacterium Infections
Actinomycetales Infections
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014