Persistency Study After aP / Tdap Booster Vaccines in Adult Subjects (V113_01 Extension 1)

• ClinicalTrials.gov Identifier: NCT02382913
• Recruitment Status: Completed
• First Posted: March 9, 2015
• Results First Posted: February 12, 2016
• Last Update Posted: March 24, 2016
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

Tracking Information

• First Submitted Date: February 27, 2015
• First Posted Date: March 9, 2015
• Results First Submitted Date: January 14, 2016
• Results First Posted Date: February 12, 2016
• Last Update Posted Date: March 24, 2016
• Study Start Date: April 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2016)

• Geometric Mean Concentrations (GMCs) of Antibodies in aP1, aP2, aP4 Groups Against Pertussis Antigens at Day 1. [ Time Frame: Day 1 ]
  The antibody response against the pertussis antigen components (PT, FHA and PRN) at day 1 as measured by Multiplex ELISA and reported as Geometric Mean Concentrations (GMCs) in aP1, aP2, aP4 Groups versus the response to the commercially available Tdap comparator. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.
• Geometric Mean Concentrations (GMCs) of Antibodies in T5D2aP1, T5D2aP2 and T5D2aP4 Groups Against Pertussis Antigens at Day 1. [ Time Frame: Day 1 ]
  The antibody response against the pertussis antigen components (PT, FHA and PRN) in serum at day 1 as measured by Multiplex ELISA and reported as Geometric Mean Concentrations (GMCs) in T5D2aP1, T5D2aP2 and T5D2aP4 Groups versus the response to the commercially available Tdap comparator. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.
• Geometric Mean Concentrations (GMCs) of Antibodies in T5D4aP1, T5D4aP2 and T5D4aP4 Groups Against Pertussis Antigens at Day 1. [ Time Frame: Day 1 ]
  The antibody response against the pertussis antigen components (PT, FHA and PRN) in serum at day 1 as measured by Multiplex ELISA and reported as Geometric Mean Concentrations (GMCs) in T5D4aP1, T5D4aP2 and T5D4aP4 Groups versus the response to the commercially available Tdap comparator. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.
• Geometric Mean Ratios Antibodies Concentrations in aP1, aP2, aP4 Groups as Measured at V113_01E1 Day 1 vs. All V113_01 Time Points. [ Time Frame: Day 1, Day 8, Day 30, Day 180, Day 365 of V113_01 and Day 1 of V113_01E1 ]
  Geometric Mean Ratios of anti-PT, anti-FHA and anti-PRN antibody were calculated to measure the changes in immunogenicity concentrations within subjects from all V113_01 time points to V113_01E1 day 1. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.
• Geometric Mean Ratios Antibodies Concentrations in T5D2aP1, T5D2aP2 and T5D2aP4 Groups as Measured at V113_01E1 Day 1 vs. All V113_01 Time Points. [ Time Frame: Day 1, Day 8, Day 30, Day 180, Day 365 of V113_01 and Day 1 of V113_01E1 ]
  Geometric Mean Ratios of anti-PT, anti-FHA and anti-PRN antibody were calculated to measure the changes in immunogenicity concentrations within subjects from all V113_01 time points to V113_01E1 day 1. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.
• Geometric Mean Ratios Antibodies Concentrations in T5D4aP1, T5D4aP2 and T5D4aP4 Groups as Measured at V113_01E1 Day 1 vs. All V113_01 Time Points. [ Time Frame: Day 1, Day 8, Day 30, Day 180, Day 365 of V113_01 and Day 1 of V113_01E1 ]
  Geometric Mean Ratios of anti-PT, anti-FHA and anti-PRN antibody were calculated to measure the changes in immunogenicity concentrations within subjects from all V113_01 time points to V113_01E1 day 1. Note: The mean and confidence intervals of Licensed Tdap for the same antigen can be different (from aP to Tdap table) since two different statistical model were fitted within each antigen: one with aP and Licensed Tdap groups and one with Tdap and Licensed Tdap groups.

Original Primary Outcome Measures (submitted: March 6, 2015)

• Geometric Mean Concentrations (GMCs) of anti-PT, anti-FHA and anti-PRN antibody at study V113_01E1 day 1. [ Time Frame: Day 1 ]
• Geometric Mean Ratios of anti-PT, anti-FHA and anti-PRN antibody for concentrations as measured at V113_01E1 day 1 vs. all V113_01 time points. [ Time Frame: V113_01E1 day 1 vs. all V113_01 time points. ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Persistency Study After aP / Tdap Booster Vaccines in Adult Subjects (V113_01 Extension 1)
• Official Title: Phase 1 Extension Study to Evaluate Antibody Persistence Approximately 3 Years After Administration of Different Dosages of Acellular Pertussis or Tetanus-Diphtheria-acellular Pertussis Booster Vaccines in Healthy Adult Subjects Enrolled in Study V113_01

Brief Summary

The purpose of this study is to evaluate the persistence of immune response against the three pertussis antigens (anti- pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN)) in subjects who received a booster dose of either aP or Tdap study vaccines or Boostrix® during V113_01 study.

There was only one Clinic Visit at day 1. Eligible subjects went undergo a single blood draw after which they were observed for approximately 15 minutes. Approximately 10.0 mL of blood was withdrawn.

No vaccine was administered and no safety data was collected in this study.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label)
• Condition: Pertussis

Intervention

• Biological: aP booster

  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.

• Biological: TdaP booster

  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.

• Biological: Licensed TdaP booster (Boostrix®)

  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.

Study Arms

• Experimental: Group 1
  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.
  Intervention: Biological: aP booster
• Experimental: Group 2
  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.
  Intervention: Biological: aP booster
• Experimental: Group 3
  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
  Intervention: Biological: aP booster
• Experimental: Group 4
  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.
  Intervention: Biological: TdaP booster
• Experimental: Group 5
  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.
  Intervention: Biological: TdaP booster
• Experimental: Group 6
  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.
  Intervention: Biological: TdaP booster
• Experimental: Group 7
  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.
  Intervention: Biological: TdaP booster
• Experimental: Group 8
  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
  Intervention: Biological: TdaP booster
• Experimental: Group 9
  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.
  Intervention: Biological: TdaP booster
• Active Comparator: Group 10
  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
  Intervention: Biological: Licensed TdaP booster (Boostrix®)

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2015): 315
• Original Estimated Enrollment (submitted: March 6, 2015): 407
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy individuals previously enrolled in V113_01 trial, who completed the study following study protocol and who received the appropriate booster vaccine per group assignment
• Individuals who voluntarily gave written informed consent after the nature of the study was explained according to local regulatory requirements, prior to study entry
• Individuals who could comply with study procedures including follow-up

Exclusion Criteria:

1. Clinical conditions representing a contraindication to blood draw.

2. Abnormal function of the immune system resulting from:

   • Clinical conditions
   • Systemic administration of corticosteroids per oral (PO)/ intravenous (IV)/ intramuscular (IM) for more than 14 consecutive days within 90 days prior to informed consent.
   • Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
3. Received immunoglobulins or any blood products within 180 days prior to informed consent.
4. Received an investigational or non-registered medicinal product within 30 days prior to informed consent
5. Study personnel as an immediate family or household member
6. Any other clinical condition that, in the opinion of the investigator, could interfere with the results of the study or pose additional risk to the subject due to participation in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 43 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT02382913
• Other Study ID Numbers: V113_01E1; 2014-003729-16 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis
• Original Responsible Party: Novartis Vaccines
• Current Study Sponsor: Novartis
• Original Study Sponsor: Novartis Vaccines
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: February 2016