The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not

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1 The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: Combined Reduced Antigen Content Diphtheria, Tetanus, Acellular Pertussis Vaccine. Study Number: Title: Immunogenicity and safety study of GSK Biologicals Boostrix vaccine using a new syringe presentation in healthy adolescents aged years. Boostrix (dtpa): GlaxoSmithKline (GSK) Biologicals' combined reduced-antigen-content diphtheria, tetanus and acellular pertussis vaccine. Rationale: The purpose of this study was to provide clinical data, in healthy adolescents, on the immunogenicity and safety of the dtpa vaccine in its new syringe presentation in comparison with the previous syringe presentation. The previous syringe dtpa vaccine was used as a benchmark to establish non-inferiority in terms of immune response to the diphtheria, tetanus and pertussis antigens. Study duration was approximately 1 month for each subject. Phase: IV Study Period: 5 July 2011 to 3 September 2012 Study Design: Single-blind, randomized (1:1), controlled, multicenter study with 2 parallel groups Centres: 3 centers: 1 center in Chile and 2 centers in Mexico. Indication: Booster immunization of healthy adolescents against diphtheria, tetanus and pertussis Treatment: Study groups were as follows: dtpa-new Group: subjects in this group, aged 10 to 15 years, received one dose of dtpa vaccine administered using the new-syringe presentation, at Day 0. dtpa-prev Group: subjects in this group, aged 10 to 15 years, received one dose of dtpa vaccine administered using the previous-syringe presentation, at Day 0. The dtpa vaccine was administered intramuscularly in the deltoid of the non-dominant arm. Objectives: To demonstrate that the dtpa vaccine administered using the new-syringe presentation was non-inferior to dtpa vaccine administered using the previous-syringe presentation, in terms of immune response to all vaccine antigens, one month after booster vaccination. Criteria for evaluation: - The upper limit (UL) of the 95% confidence interval (CI) on the geometric mean concentration (GMC) ratios [dtpa-prev Group over dtpa-new Group] for anti-diphtheria (anti-d), anti-tetanus (anti-t), anti-pertussis toxoid (anti-pt), anti-filamentous haemagglutinin (anti-fha) and anti-pertactin (anti-prn) antibodies was 1.5 (clinical limit for non-inferiority). Primary Outcome/Efficacy Variable: Immunogenicity with respect to the components of the study vaccines: One month after booster vaccination: Anti-D, anti-t, anti-pt, anti-fha and anti-prn antibody concentrations. Secondary Outcome/Efficacy Variable(s): Immunogenicity with respect to the components of the study vaccines: Prior to and one month after booster vaccination: Anti-D, anti-t, anti-pt, anti-prn, anti-fha seroprotection/seropositivity status. One month after booster vaccination: Booster response * to all vaccine antigens. Solicited local and general symptoms: Occurrence of solicited local and general symptoms during the 4-day (Day 0 Day 3) follow-up period after booster vaccination. Unsolicited adverse events (AEs): Occurrence of unsolicited symptoms during the 31-day (Day 0 Day 30) follow up period after booster vaccination. Serious adverse events (SAEs): Occurrence of SAEs from the booster dose up to study end. Definitions for seronegativity, seropositivity and seroprotection were as follows: A seronegative subject was defined as a subject whose antibody concentration was < the assay cut-off.

2 A seropositive subject was defined as a subject whose antibody concentration was the assay cut-off. Applicable thresholds were, for anti-pt, anti-fha and anti-prn antibody concentrations, 5 EL.U/mL. A seroprotected subject was defined as a subject whose antibody concentration was the level defining clinical protection. Applicable thresholds were, for anti-d and anti-t antibody concentrations, 0.1 IU/mL (by Enzyme- Linked Immunosorbent Assay [ELISA]). * 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. *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. 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. Statistical Methods: The analyses were performed on the Total Vaccinated cohort and the According To Protocol (ATP) cohort for immunogenicity. - The Total Vaccinated cohort included all subjects with documented administration of the study vaccine. - The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol and with no elimination criteria) for whom data concerning immunogenicity outcome measures were available. Analysis of Immunogenicity The analysis was performed on the ATP cohort for immunogenicity To demonstrate that the dtpa vaccine administered with the new-syringe presentation was non-inferior to the dtpa vaccine administered with the previous-syringe presentation, 95% CI for the GMC ratio of the two groups [dtpa-prev Group over dtpa-new Group] for all vaccine antigens was computed one month after booster vaccination using analysis of co-variance (ANCOVA) model. The GMC obtained from this ANCOVA model was adjusted for pre-booster concentration. In addition, for each group, at each time point that a blood sample result was available: Seroprotection/seropositivity rates with 95% CI for antibodies against D, T, PT, FHA and PRN were tabulated. GMCs with 95% CI for antibodies against all vaccine antigens were calculated. Booster responses for anti-d, anti-t, anti-pt, anti-fha and anti-prn antibodies were also tabulated with 95% CI. Analysis of Safety The percentages of subjects reporting each individual local and general solicited symptom within the 4-day (Days 0-3) following vaccination were tabulated, with exact 95% CI. The same tabulation was performed for grade 3 solicited symptoms and for general solicited symptoms assessed by the investigator as causally related to the study vaccine. The percentage of subjects with unsolicited AEs, classified by the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms, within the 31-day (Days 0-30) following vaccination was tabulated. The percentage of subjects with SAEs, classified by MedDRA preferred terms, was tabulated for the entire study period. Study Population: Healthy males or females subjects aged between 10 and 15 years of age at the time of booster vaccination were enrolled in the study. Subjects who had previously received 6 doses of vaccine either against diphtheria, tetanus, and pertussis or against diphtheria, tetanus and acellular pertussis, in line with local recommendations. Subjects were excluded if matching any of the following exclusion criteria: child in care; history of previous or intercurrent diphtheria, tetanus or pertussis disease, chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to vaccination; administration of a vaccine unforeseen by the study protocol within 30 days of vaccination with some exception for the influenza vaccine; hyper sensitivity to component(s) of the study vaccine; occurrence of AE after a previous administration of a dtpa vaccine. Female subjects of childbearing potential were enrolled in the study, provided the subject had a negative pregnancy test on the day of vaccination, and practiced adequate contraception for 30 days prior to vaccination and during the entire treatment period and for 2 months after the booster vaccination. Written informed consent was obtained before study entry from the parent(s)/legally accepted representative(s) (LAR(s)) of the subject prior to study entry. Additional written informed assent was obtained also from the subject, if required by local regulations. Number of Subjects: dtpa-new Group dtpa-prev Group

3 Planned, N Randomised, N (Total Vaccinated cohort) Completed, n (%) 330 (98.5) 329 (97.9) Total Number Subjects Withdrawn, N (%) 5 (1.5) 7 (2.1) Withdrawn due to Adverse Events n (%) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy n (%) Not Applicable Not Applicable Withdrawn for other reasons n (%) 5 (1.5) 7 (2.1) Demographics dtpa-new Group dtpa-prev Group N (Total Vaccinated cohort) Sex, n (%) 179 (53.4) 178 (53.0) Females: Males: 156 (46.6) 158 (47.0) Mean Age, years (SD) 11.9 (1.59) 11.9 (1.61) Median Minimum, Maximum 10, 15 10, 15 Mixed Origin, n (%) 178 (53.1) 174 (51.8) Primary Efficacy Results: Adjusted ratios of GMCs for anti-d and anti-t between groups (dtpa-prev Group divided by dtpa-new Group) one month after booster vaccination, with their 95% CIs (ATP cohort for immunogenicity) Adjusted GMC ratio (dtpa-prev Group / dtpa-new Group) dtpa-prev Group dtpa-new Group 95% CI Antibody N Adjusted N Adjusted Value LL UL GMC GMC Anti-D Anti-T N = Number of subjects with both pre- and post-vaccination results available Adjusted GMC = geometric mean antibody concentration obtained from an ANCOVA model adjusted for pre-booster concentration 95% CI = 95% confidence interval; LL = lower limit, UL = upper limit Criterion for evaluation of non-inferiority: UL of 95% CI 1.5 Primary Efficacy Results: Adjusted ratios of GMCs for anti-pt, anti-fha and anti-prn between groups (dtpa-prev Group divided by dtpa-new Group) one month after booster vaccination, with their 95% CIs (ATP cohort for immunogenicity) Adjusted GMC ratio (dtpa-prev Group / dtpa-new Group) dtpa-prev Group dtpa-new Group 95% CI Antibody N Adjusted N Adjusted Value LL UL GMC GMC Anti-PT Anti-FHA Anti-PRN N = Number of subjects with both pre- and post-vaccination results available Adjusted GMC = geometric mean antibody concentration obtained from an ANCOVA model adjusted for pre-booster concentration 95% CI = 95% confidence interval; LL = lower limit, UL = upper limit Criterion for evaluation of non-inferiority: UL of 95% CI 1.5 Primary Efficacy Results: Seroprotection rates and GMCs for anti-d and anti-t antibodies before and one month after the booster vaccination (ATP cohort for immunogenicity) 0.1 IU/mL 1 IU/mL GMC (IU/mL)* 95% CI 95% CI 95% CI

4 Antibody Group Timing N n % LL UL n % LL UL value LL UL Anti-D dtpa-new PRE POST* dtpa-prev PRE POST* Anti-T dtpa-new PRE POST* dtpa-prev PRE POST* Seroprotection=anti-D and anti-t antibody concentration 0.1 IU/mL GMC = geometric mean antibody concentration calculated on all subjects N = number of subjects with available results n(%)=number(percentage) of subjects with antibody concentrations above the specified cut-off 95% CI = 95% confidence interval; LL = lower limit, UL = upper limit PRE=Pre-booster blood sampling time point POST=Post-booster blood sampling time point * Primary efficacy variable. Primary Efficacy Results: Seropositivity rates and GMCs for anti-pt, anti-fha and anti-prn antibodies before and one month after the booster vaccination (ATP cohort for immunogenicity) 5 EU/mL GMC (EU/mL)* 95% CI 95% CI Antibody Group Timing N n % LL UL value LL UL Anti-PT dtpa-new PRE POST* dtpa-prev PRE POST* Anti-FHA dtpa-new PRE POST* dtpa-prev PRE POST* Anti-PRN dtpa-new PRE POST* dtpa-prev PRE POST* Seropositive=anti-PT, anti-fha and anti-prn antibodies 5 EU/mL GMC = geometric mean antibody concentration calculated on all subjects N = number of subjects with available results n(%)=number(percentage) of subjects with antibody concentrations above the specified cut-off 95% CI = 95% confidence interval; LL = lower limit, UL = upper limit PRE=Pre-booster blood sampling time point POST=Post-booster blood sampling time point * Primary efficacy variable. Secondary Outcome Results: Booster responses for anti-d and anti-t antibody concentration one month after the booster vaccination (ATP cohort for immunogenicity) Booster response 95% CI Antibody Group Pre-vaccination N n % LL UL status Anti-D dtpa-new S S Total dtpa-prev S S Total Anti-T dtpa-new S

5 S Total dtpa-prev S S Total S- = seronegative subjects (antibody concentration < 0.1 IU/mL for anti-d, anti-t) prior to vaccination S+ = seropositive subjects (antibody concentration 0.1 IU/mL for anti-d, anti-t) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination Booster response defined as : For initially seronegative subjects, antibody concentration 0.4 IU/mL at post vaccination timepoint For initially seropositive subjects : antibody concentration at POST 4 fold the pre-vaccination antibody concentration N = number of subjects with both pre- and post-vaccination results available n/% = number/percentage of subjects with a booster response 95% CI = exact 95% confidence interval, LL = lower limit, UL = upper limit Secondary Outcome Results: Booster responses for anti-pt, anti-fha and anti-prn antibody concentration one month after the booster vaccination (ATP cohort for immunogenicity) Booster response 95% CI Antibody Group Pre-vaccination N n % LL UL status Anti-PT dtpa-new S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total dtpa-prev S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total Anti-FHA dtpa-new S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total dtpa-prev S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total Anti-PRN dtpa-new S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total dtpa-prev S S+ (<20 EU/mL) S+ ( 20 EU/mL) Total S- = seronegative subjects (antibody concentration < 5 EU/mL for anti-pt, anti-fha and anti-prn) prior to vaccination S+ = seropositive subjects (antibody concentration 5 EU/mL for anti-pt, anti-fha and anti-prn) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination Booster response defined as : For initially seronegative subjects, antibody concentration 20 EU/mL at post vaccination timepoint For initially seropositive subjects with pre-vaccination antibody concentration < 20 EU/mL : antibody concentration at post vaccination 4 fold the pre-vaccination antibody concentration For initially seropositive subjects with pre-vaccination antibody concentration 20 EU/mL : antibody concentration at post vaccination 2 fold the pre-vaccination antibody concentration N = number of subjects with both pre- and post-vaccination results available n/% = number/percentage of subjects with a booster response

6 95% CI = exact 95% confidence interval, LL = lower limit, UL = upper limit Secondary Outcome Results: Number (%) of subjects with solicited local symptoms during the 4-day (Days 0-3) postvaccination period (Total Vaccinated cohort) dtpa-new Group dtpa-prev Group 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL Pain Any Grade Redness Any >50 mm Swelling Any >50 mm N = number of subjects with the documented dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = Incidence of any particular symptom regardless of intensity grade Grade 3 Pain = Significant pain at rest. Prevented normal every day activities. Secondary Outcome Results: Number (%) of subjects with solicited general symptoms during the 4-day (Days 0-3) postvaccination period (Total Vaccinated cohort) dtpa-new Group dtpa-prev Group 95 % CI 95 % CI Symptom Intensity/Relationship N n % LL UL N n % LL UL Fatigue Any Grade Related Gastrointestinal symptoms Any Grade Related Headache Any Grade Related Temperature (Axillary) Any >39.0 C Related N = number of subjects with the documented dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = Incidence of any particular symptom regardless of intensity grade or relationship to study vaccination Related = Symptom which was assessed by the investigator as related to vaccination Grade 3 symptom = Symptom that prevented normal activity Note: Gastrointestinal symptoms included Nausea, Vomiting, Diarrhea and or Abdominal pain Safety Results: Number (%) of subjects with unsolicited AEs (Total Vaccinated cohort) Most frequent adverse events - On-Therapy (occurring within Days 0-30 following vaccination) dtpa-new Group N = 335 Subjects with any AE(s), n (%) 44 (13.1) 45 (13.4) Nasopharyngitis 5 (1.5) 5 (1.5) Gastroenteritis 3 (0.9) 5 (1.5) Tonsillitis 2 (0.6) 4 (1.2) Influenza 3 (0.9) 2 (0.6) Headache 2 (0.6) 2 (0.6) Toothache - 4 (1.2) Bronchitis 1 (0.3) 2 (0.6) Dizziness 1 (0.3) 2 (0.6) Dysmenorrhoea - 3 (0.9) Rash 2 (0.6) 1 (0.3) dtpa-prev Group N = 336

7 Abdominal pain 1 (0.3) 1 (0.3) Abdominal pain upper 1 (0.3) 1 (0.3) Animal bite 1 (0.3) 1 (0.3) Conjunctivitis 2 (0.6) - Cough 1 (0.3) 1 (0.3) Diarrhoea 1 (0.3) 1 (0.3) Myalgia 1 (0.3) 1 (0.3) Skin infection 1 (0.3) 1 (0.3) Varicella 1 (0.3) 1 (0.3) Acute tonsillitis 1 (0.3) - Adnexa uteri pain 1 (0.3) - Anaemia 1 (0.3) - Asthma 1 (0.3) - Bronchitis viral 1 (0.3) - Chest pain - 1 (0.3) Dermatitis 1 (0.3) - Food poisoning 1 (0.3) - Forearm fracture - 1 (0.3) H1N1 influenza - 1 (0.3) Head injury 1 (0.3) - Hypersensitivity 1 (0.3) - Injection site pain 1 (0.3) - Injury 1 (0.3) - Joint injury 1 (0.3) - Lice infestation - 1 (0.3) Ligament sprain - 1 (0.3) Lymphadenitis 1 (0.3) - Nasal congestion - 1 (0.3) Otitis media - 1 (0.3) Pain in extremity - 1 (0.3) Palpitations - 1 (0.3) Pharyngitis 1 (0.3) - Pneumonia 1 (0.3) - Respiratory tract infection - 1 (0.3) Scar pain 1 (0.3) - Syncope 1 (0.3) - Upper respiratory tract infection 1 (0.3) - Viral infection 1 (0.3) - Vomiting - 1 (0.3) Wound 1 (0.3) - - = AE absent Safety Results: Number (%) of subjects with SAEs during the entire study period (Total Vaccinated cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication]serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs dtpa-new Group N = 335 dtpa-prev Group N = 336 Subjects with any SAE(s), n (%) [n assessed by the investigator as 1 (0.3) [0] 0 (0.0) [0] related] Injury 1 (0.3) [0] 0 (0.0) [0] Fatal SAEs dtpa-new Group dtpa-prev Group Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related] 0 (0.0) [0] 0 (0.0) [0] Conclusion: The criteria for evaluation of the primary objectives were met. One month after booster vaccination, all ULs of the 95% CIs

8 on the adjusted GMC ratio for all antigens were 1.5 (clinical limit for non-inferiority): the ULs for the adjusted GMC ratio [dtpa-prev Group over dtpa-new Group] for anti-d, anti-t, anti-pt, anti-fha and anti-prn were respectively 1.09, 1.11, 1.05, 1.03 and At the same timepoint, the GMCs for anti-d was and 6.493; for anti-t, and ; for anti-pt, and 125.9; for anti-fha, and and for anti-prn, and for the dtpa-new and dtpa-prev groups, respectively. Within the 30-days (Days 0-30) follow-up period after vaccination, at least 1 unsolicited AE was reported for 44 (13.1%) and 45 (13.4%) subjects in the dtpa-new and dtpa-prev groups, respectively. During the entire study period, SAEs were reported for 1 (0.3%) subject in the dtpa-new Group and 0 (0.0%) subjects in the dtpa-prev Group. No fatal SAEs were reported during the entire study period. Date updated: 20-February-2014