Immunogenicity and Safety of BoostrixTM Using a New Syringe in 10 to 15-year Old Adolescents

• ClinicalTrials.gov Identifier: NCT01362322
• Recruitment Status: Completed
• First Posted: May 30, 2011
• Results First Posted: August 10, 2018
• Last Update Posted: August 10, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: May 19, 2011
• First Posted Date: May 30, 2011
• Results First Submitted Date: March 23, 2017
• Results First Posted Date: August 10, 2018
• Last Update Posted Date: August 10, 2018
• Study Start Date: July 1, 2011
• Actual Primary Completion Date: September 3, 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 31, 2018)

• Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Month 1 ]
  Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
• Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Month 1 ]
  Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter(EL.U/mL)
• Anti-diphteria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Day 0 ]
  Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL).
• Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN) Antibody Concentrations [ Time Frame: At Day 0 ]
  Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL).

• Original Primary Outcome Measures (submitted: May 26, 2011): Immunogenicity with respect to the components of the study vaccine in terms of antibody concentrations [ Time Frame: One month after booster vaccination (Month 1) ]

Current Secondary Outcome Measures (submitted: July 31, 2018)

• Number of Seropositive Subjects Against Diphtheria (D) and Tetanus (T) Antigens [ Time Frame: At Day 0 (PRE) and at Month 1 (POST) ]
  A seroprotected subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 0.1. international units per milliliter (IU/mL), as assessed by the Enzyme Linked Immunosorbent Assay (ELISA).
• Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigens [ Time Frame: At Day 0 (PRE) vaccine and at Month 1 (POST) ]
  A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentration greater than or equal to ( ≥) 1 international units per milliliter (IU/mL).
• Number of Seropositive Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations) [ Time Frame: At Day 0 (PRE) vaccine and at Month 1 (POST) ]
  A seroprotected subject was defined as a subject whose antibody concentration was greater than or equal to (≥) 5 Enzyme Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL).
• Number of Subjects With Booster Response to Diphtheria (D) and Tetanus (T) Antibodies [ Time Frame: At Month 1 ]
  Booster response to the diphtheria and tetanus antigens, was defined as: for initially seronegative subjects (pre-vaccination concentration <0.1 IU/mL): antibody concentrations at least 4 times the cut-off (post-vaccination concentration ≥ 0.4 IU/mL); for initially seropositive subjects (pre-vaccination concentration ≥ 0.1 IU/mL): an increase in antibody concentrations of at least 4 times the pre-vaccination concentration.
• Number of Subjects With a Booster Response to Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA), Pertactin (PRN) Antigens. [ Time Frame: At Month 1 ]
  Booster response to the PT, FHA and PRN antigens, was defined as: for initially seronegative subjects: antibody concentrations at least 4 times the cut-off (post-vaccination concentration ≥ 20 EL.U/mL); for initially seropositive subjects with pre-vaccination concentration ≥ 5 EL.U/mL and < 20 EL.U/mL: an increase in antibody concentrations of at least 4 times the pre-vaccination concentration; and for initially seropositive subjects with pre-vaccination concentration ≥ 20 EL.U/mL: an increase in antibody concentrations of at least 2 times the pre-vaccination concentration.
• Number of Subjects With Any Solicited Local Symptoms [ Time Frame: Within 4 days (Days 0-3) post vaccination period ]
  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
• Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days (Days 0-30) post ]
  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
• Number of Subjects With Any Solicited General Symptoms [ Time Frame: Within 4 days (Days 0-3) post vaccination period ]
  Assessed solicited general symptoms were fatigue, temperature [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], headache and gastrointestinal symptoms. Gastrointestinal symptoms included Nausea, Vomiting, Diarrhea and or Abdominal pain. Any = occurrence of the symptom regardless of intensity grade.
• Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 - Month 1) ]
  Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Original Secondary Outcome Measures (submitted: May 26, 2011)

• Immunogenicity with respect to the components of the study vaccine in terms of number of seroprotected/seropositive subjects [ Time Frame: Prior to (Day 0) and one month after booster vaccination (Month 1) ]
• Number of subjects with solicited local and general symptoms [ Time Frame: During the 4-day (Day 0- Day 3) follow-up period after booster vaccination ]
• Number of subjects with unsolicited adverse events [ Time Frame: During the 31-day (Day 0- Day 30) follow-up period after booster vaccination ]
• Number of subjects with serious adverse events [ Time Frame: From the booster dose up to study end (Day 0 to Month 1) ]
• Immunogenicity with respect to the components of the study vaccine in terms of number of subjects with a booster response [ Time Frame: One month after booster vaccination (Month 1) ]

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

Descriptive Information

• Brief Title: Immunogenicity and Safety of BoostrixTM Using a New Syringe in 10 to 15-year Old Adolescents
• Official Title: Immunogenicity and Safety Study of GSK Biologicals' Boostrix™ Vaccine Using a New Syringe Presentation in Healthy Adolescents Aged 10-15 Years
• Brief Summary: The purpose of the study is to compare the immunogenicity and safety of a booster dose of BoostrixTM administered in a new syringe presentation to that of BoostrixTM administered in the previous syringe presentation in healthy adolescents aged 10-15 years.

Detailed Description

The protocol has been updated following Protocol amendment 1 date 03 August 2011 leading to the update of the exclusion criteria to allow subjects in Mexico to receive the flu vaccine in accordance with the local standard of care.

The protocol has been updated following Protocol amendment 2 dated 14 December 2011 due to the recruitment constraints as a result of the DT/dTpa vaccination campaign in the countries. The inclusion and exclusion criteria were amended to allow the participation of those who have already received the 6th dose of the diphtheria, tetanus and/or pertussis containing vaccine.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Prevention

Condition

• Diphtheria
• Tetanus
• Acellular Pertussis

Intervention

• Biological: Boostrix TM (new syringe presentation)
  Single dose, intramuscular administration in a new syringe presentation
• Biological: Boostrix TM (previous syringe presentation)
  Single dose, intramuscular administration in previous syringe presentation

Study Arms

• Experimental: BOOSTRIX NEW GROUP
  Subjects, aged 10 to 15 years, received one dose of Boostrix™ vaccine administered using a new syringe presentation (prefilled syringes from a different manufacturer) in the deltoid of the non-dominant arm, at Day 0.
  Intervention: Biological: Boostrix TM (new syringe presentation)
• Active Comparator: BOOSTRIX PREV GROUP
  Subjects, aged 10 to 15 years, received one dose of Boostrix™ vaccine administered using a previous syringe presentation (single dose vial or a prefilled disposable syringe without a needle) in the deltoid of the non-dominant arm, at Day 0.
  Intervention: Biological: Boostrix TM (previous syringe presentation)

• Publications *: Pavia-Ruz N, Abarca K, Lepetic A, Cervantes-Apolinar MY, Hardt K, Jayadeva G, Kuriyakose S, Han HH, de la O M. Evaluation of a new syringe presentation of reduced-antigen content diphtheria, tetanus, and acellular pertussis vaccine in healthy adolescents--A single blind randomized trial. Hum Vaccin Immunother. 2015;11(7):1770-4. doi: 10.1080/21645515.2015.1041697.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 11, 2012): 671
• Original Estimated Enrollment (submitted: May 26, 2011): 690
• Actual Study Completion Date: September 3, 2012
• Actual Primary Completion Date: September 3, 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject's parent(s)/Legally Acceptable Representative(s) and subjects who the investigator believes can and are willing to comply with the requirements of the protocol.
• A male or female between 10 and 15 years of age at the time of booster vaccination.
• Prior to protocol amendment 2, subjects who have previously received 5 doses of diphtheria-tetanus-pertussis vaccine (whole cell/acellular [w/a]) as part of primary and booster vaccination, in line with local recommendations.
• After protocol amendment 2, subjects who have previously received 6 doses of either DT(P) (w/a)/ dTpa vaccine as part of primary and booster vaccination, in line with local recommendations.
• Healthy subjects as determined by the investigator based on medical history and clinical examination before entering into the study.
• Written informed consent to be obtained before study entry from the parent(s)/ Legally Acceptable Representative(s) of the subject.
• Written informed assent to be obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative(s), if required by local regulations.
• Female subjects of non-childbearing potential may be enrolled in the study.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

  • has a negative pregnancy test on the day of vaccination,
  • if sexually active, has practiced adequate contraception for 30 days prior to vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after booster vaccination.

Exclusion Criteria:

• Child in care.
• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the booster dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the booster dose of vaccine - with the exception of influenza vaccine which is allowed up to 7 days before the study vaccine dose, or planned in the period ≥ 7 days after the study vaccine dose.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• A history of previous or intercurrent diphtheria, tetanus or pertussis disease.
• A history of vaccination against these diseases since the 5th or the 6th dose of DT(P)/dT(pa). For subjects who have received the 6th dose of the diphtheria, tetanus and/or pertussis containing vaccine, the interval between the last DT(P)/dT(pa) vaccination and the administration of the study vaccine should be at least 18 months.

• Occurrence of any of the following adverse event after a previous administration of a Boostrix vaccine :

  • known hypersensitivity to any component of the vaccine, or have shown signs of hypersensitivity after previous administration of diphtheria, tetanus or pertussis vaccines,
  • encephalopathy of unknown aetiology occurring within 7 days following previous vaccination with pertussis-containing vaccine,
  • transient thrombocytopenia or neurological complications following an earlier immunisation against diphtheria and/or tetanus.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Acute disease and/or fever at the time of enrolment.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions, if applicable.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 15 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Chile, Mexico

Administrative Information

• NCT Number: NCT01362322
• Other Study ID Numbers: 114778
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

• Responsible Party: GlaxoSmithKline
• Study Sponsor: GlaxoSmithKline
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: May 2018