Clinical trial NCT01529645: Safety and Dose Ranging Study of Acellular Pertussis and Acellular Pertussis -Tetanus-Diphtheria Booster Vaccines in Healthy Adults Ages 18 to 40 Years
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pertussis
Whooping Cough
Tetanus
Lockjaw
Diphtheria
Keywords: pertussis
booster vaccine
tetanus
diphtheria in adults
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-02-09
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: The Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine
timeFrame: Day 1 through 7 after vaccination
measure: The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine
timeFrame: From day 1 to day 365
measure: Geometric Mean Concentrations (GMCs) of Antibodies in aP1, aP2, aP4 Groups Against Pertussis Antigens Following Booster Vaccination
timeFrame: Day 1 (baseline) and Day 30 post vaccination
measure: GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Groups Against Pertussis Antigens Following Booster Vaccination
timeFrame: Day 1 (baseline) and Day 30 post vaccination
measure: GMCs of Antibodies in T5D4aP1, T5D4aP2 and T5D4aP4 Groups Against Pertussis Antigens Following Vaccination
timeFrame: Day 1 (baseline) and Day 30 post vaccination
measure: Geometric Mean Ratios (GMRs) of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in aP1, aP2, aP4 Booster Groups Against Pertussis Antigens
timeFrame: Day 30 post vaccination/baseline (Day 1)
measure: GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Booster Groups Against Pertussis Antigens
timeFrame: Day 30 post vaccination/baseline (Day 1)
measure: GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies for T5D4aP1, T5D4aP2 and T5D4aP4 Booster Groups Against Pertussis Antigens
timeFrame: Day 30 post vaccination/baseline (Day 1)
measure: Percentages of Subjects With Diphtheria and Tetanus Antitoxin Units >= 0.1/mL After Vaccination
timeFrame: Day 1 (baseline) and Day 30 post vaccination
Secondary outcomes:
measure: Percentages of Subjects With 2- and 4-fold Increase in GMCs Against Pertussis Antigens Following Vaccination.
timeFrame: Day 30 post vaccination
measure: GMCs of Antibodies Against Diphtheria and Tetanus Antigens Following Vaccination
timeFrame: Day 1 (baseline) and Day 30 post vaccination
measure: GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies Against Diphtheria and Tetanus Antigens
timeFrame: Day 30 post vaccination/Day 1
Other outcomes:
Locations:
city: De Pintelaan
country: Belgium
facility: Center for Vaccinology (CEVAC), Ghent University Hospital
state: B-9000 Ghent
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
affiliation: Center for Vaccinology (CEVAC), Ghent University Hospital
name: Geert Leroux-Roels, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leroux-Roels G, Lattanzi M, Solis CD, Contorni M, Costantini M, Moraschini L, Bardelli M, Bertholet S, Borgogni E, Buricchi F, Cantisani R, Faenzi E, Finco O, Leuzzi R, Pizza M, Rosa D, Schiavetti F, Seubert A, Spensieri F, Volpini G, Zedda L, Giudice GD, Galgani I. A phase I, randomized, controlled, dose-ranging study of investigational acellular pertussis (aP) and reduced tetanus-diphtheria-acellular pertussis (TdaP) booster vaccines in adults. Hum Vaccin Immunother. 2018 Jan 2;14(1):45-58. doi: 10.1080/21645515.2017.1385686. Epub 2017 Nov 27.