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

Tetanus Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01529645
• Other study ID #: V113_01
• Secondary ID: 2011-000688-28
• Status: Completed
• Phase: Phase 1
• First received: February 6, 2012
• Last updated: September 16, 2014
• Start date: March 2012
• Est. completion date: July 2013

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: July 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diphtheria
• Lockjaw
• Pertussis
• Tetanus
• Whooping Cough

Intervention

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.
• 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.
• Licensed TdaP booster vaccine
Licenced TdaP booster vaccine was administered intramuscularly in the upper deltoid region of the subject's non-dominant arm.
• 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.

Other:
• Saline solution
Subjects received one injection of saline solution at one month after vaccination.

Locations

Country	Name	City	State
Belgium	Center for Vaccinology (CEVAC), Ghent University Hospital	De Pintelaan	B-9000 Ghent

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine	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.	Day 1 through 7 after vaccination	Yes
Primary	The Number of Subjects Reporting Unsolicited Adverse Events After Receiving Different Formulations of aP and TdaP Booster Vaccine	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.	From day 1 to day 365	Yes
Primary	Geometric Mean Concentrations (GMCs) of Antibodies in aP1, aP2, aP4 Groups Against Pertussis Antigens Following Booster Vaccination	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.	Day 1 (baseline) and Day 30 post vaccination	No
Primary	GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Groups Against Pertussis Antigens Following Booster Vaccination	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.	Day 1 (baseline) and Day 30 post vaccination	No
Primary	GMCs of Antibodies in T5D4aP1, T5D4aP2 and T5D4aP4 Groups Against Pertussis Antigens Following Vaccination	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.	Day 1 (baseline) and Day 30 post vaccination	No
Primary	Geometric Mean Ratios (GMRs) of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in aP1, aP2, aP4 Booster Groups Against Pertussis Antigens	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.	Day 30 post vaccination/baseline (Day 1)	No
Primary	GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Booster Groups Against Pertussis Antigens	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.	Day 30 post vaccination/baseline (Day 1)	No
Primary	GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies for T5D4aP1, T5D4aP2 and T5D4aP4 Booster Groups Against Pertussis Antigens	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.	Day 30 post vaccination/baseline (Day 1)	No
Primary	Percentages of Subjects With Diphtheria and Tetanus Antitoxin Units >= 0.1/mL After Vaccination	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.	Day 1 (baseline) and Day 30 post vaccination	No
Secondary	Percentages of Subjects With 2- and 4-fold Increase in GMCs Against Pertussis Antigens Following Vaccination.	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.	Day 30 post vaccination	No
Secondary	GMCs of Antibodies Against Diphtheria and Tetanus Antigens Following Vaccination	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.	Day 1 (baseline) and Day 30 post vaccination	No
Secondary	GMRs of Post Vaccination Versus Pre Vaccination GMCs of Antibodies Against Diphtheria and Tetanus Antigens	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.	Day 30 post vaccination/Day 1	No