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

NCT ID: NCT01529645

Last Updated: 2016-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2013-07-31

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.

Conditions

Pertussis; Whooping Cough; Tetanus; Lockjaw; Diphtheria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Acellular pertussis vaccine

Intervention Type: BIOLOGICAL

Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.

Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

Acellular pertussis vaccine

Intervention Type: BIOLOGICAL

Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.

Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

Acellular pertussis vaccine

Intervention Type: BIOLOGICAL

Acellular pertussis (aP) vaccine was administered with different antigen doses intramuscularly in the upper deltoid region of the subject's non-dominant arm.

Diphtheria and tetanus vaccine (adsorbed, reduced antigen content, Germany)

Intervention Type: BIOLOGICAL

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.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: EXPERIMENTAL

Tetanus, reduced diphtheria, and acellular pertussis vaccine (adsorbed)

Intervention Type: BIOLOGICAL

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.

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

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.

Group Type: ACTIVE_COMPARATOR

Licensed TdaP booster vaccine

Intervention Type: BIOLOGICAL

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

Saline solution

Intervention Type: OTHER

Subjects received one injection of saline solution at one month after vaccination.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Licensed TdaP booster vaccine

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

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Saline solution

Subjects received one injection of saline solution at one month after vaccination.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Vaccines

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Vaccines

Role: STUDY_CHAIR

Novartis Vaccines

Geert Leroux-Roels, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Center for Vaccinology (CEVAC), Ghent University Hospital

Locations

Center for Vaccinology (CEVAC), Ghent University Hospital

De Pintelaan, B-9000 Ghent, Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 29172945 (View on PubMed)

Other Identifiers

2011-000688-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V113_01

Identifier Type: -

Identifier Source: org_study_id