Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

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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. Study No.: (MeMuRu-OKA-043) Title: A phase III, partially blind, randomized, primary vaccination study to assess the immunogenicity and safety of three different lots of GlaxoSmithKline (GSK) Biologicals live attenuated measles-mumps-rubella-varicella vaccine (MeMuRu- OKA), when given as a two-dose schedule to healthy children in their second year of life. MeMuRu-OKA: GSK Biologicals' combined measles, mumps, rubella and varicella vaccine. Rationale: The aim of the study was to evaluate in a clinical setting the use of lots stored at +2C to +8C for several months, which mumps titres had decreased to s close to the proposed minimum or end of shelf life titres ( aged lots). GSK Biologicals Priorix and Varilrix were used as benchmarks. MMR (Priorix): GSK Biologicals' measles-mumps-rubella vaccine, V (Varilrix): GSK Biologicals' varicella vaccine. Phase: III Study Period: 11 May 2005 to 21 November 2005 Study Design: Partially blind*, randomized, controlled study with 4 parallel groups (2:2:2:1 ratio). *The study was carried out in a double-blind manner with respect to the 3 MeMuRu-OKA lots, open with respect to s MeMuRu-OKA lots A-B-C versus MMR_V. Centers: 51 centers in 4 countries: Finland, Germany, Greece and Poland. Indication: Active immunization of healthy children during their second year of life against measles, mumps, rubella and varicella diseases. Treatment: The 4 treatment groups were as follows: received 2 doses of MeMuRu OKA vaccine lot A ( fresh lot stored at -25C after release): one at Day 0 and one at Week 6, received 2 doses of MeMuRu OKA vaccine lot A ( aged lot stored at +2C to +8C after release): one at Day 0 and one at Week 6, received 2 doses of MeMuRu OKA vaccine lot B ( aged lot stored at +2C to+8c after release): one at Day 0 and one at Week 6, MMR_V received a first dose of MMR administered concomitantly with one dose of V at Day 0 and a second dose of MMR at Week 6. All vaccines were administered subcutaneously in the deltoid region of the arm, MMR-OKA & MMR in the left arm, V in the right arm. Objectives: To establish an observed seroconversion rate for mumps of at least 90% for each lot after the first dose by neutralization assay. Primary Outcome/Efficacy Variable: Mumps seroconversion rate after the first dose by neutralization assay defined as the percentage of subjects with anti-mumps titers 28 Estimated Dose50 (ED50). Secondary Outcome/Efficacy Variable(s): Immunogenicity Mumps seroconversion rate after the first dose by ELISA, defined as the percentage of subjects with anti-mumps titers 231 U/mL Seroconversion rates after the first dose defined as the percentage of subjects with: - Anti-measles titers 150 miu/ml, - Anti-rubella titers 4 IU/mL, - Anti-varicella titers 1: 4. Measles, mumps*, rubella and varicella seroconversion rates after the second dose. Measles, mumps, rubella and varicella Geometric Mean Titers (GMTs) after each dose. * Mumps seroconversion rate by neutralization assay and ELISA. Safety Occurrence of any and Grade 3 solicited local symptoms (injection site's redness, pain and swelling) within 4 days (Day 0-3) after each vaccination. Occurrence of any, Grade 3 and vaccine-related solicited general symptoms within 43 days (Day 0-42) after each

2 vaccination in terms of fever, rash, any sign of meningism including febrile convulsion and parotitis. Occurrence of any, Grade 3 and vaccine-related unsolicited adverse events (AEs) within 43 days (Day 0-42) after each vaccination. Occurrence of serious adverse events (SAEs) throughout the entire study period (Day 0 to Week 12). 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 vaccinated subjects with at least one vaccine administration documented. The ATP Cohort for immunogenicity included all subjects who received at least one dose of study /comparator vaccine, for whom administration site of study vaccine/comparator was correct, who did not receive a vaccine not specified or forbidden in the protocol, with pre-vaccination and with post serology data available for at least one of the vaccine antigens, who were seronegative to at least one vaccine antigen at baseline and who complied with protocol procedures. Analysis of immunogenicity The analysis was performed on the ATP Cohort for immunogenicity. For each treatment group, at each blood sampling time point, seroconversion rates with exact 95% confidence intervals (CIs) and GMTs with s were calculated for each antigen after each dose by pre vaccination serological status (seropositive/seronegative). Subjects without a pre vaccination result were not included in the analysis. Analysis of safety The analysis was performed on the Total Vaccinated Cohort. The number and percentage of subjects (with exact s) with each local solicited symptom (any and Grade 3) during the 4-day (Day 0-3) follow-up period after each vaccination were tabulated for each group. The number and percentage of subjects with each general solicited symptom (any, Grade 3 and related) during the 43-day (Day 0-42) follow-up period after each vaccination were tabulated for each group. The number and percentage of subjects with unsolicited AEs (any, Grade 3 and related) during the 43-day (Day 0-42) follow-up period after each vaccination were tabulated per group according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms. The occurrence of SAEs during the entire study period was tabulated per group according to the MedDRA preferred terms. Study Population: Healthy male or female children between 11 and 21 months of age at the time of first vaccination, free of obvious health problems as established by medical history and clinical examination before entering into the study and with no history of measles, mumps, rubella and/or varicella vaccination and/or disease. Written informed consent was obtained from parent(s)/guardian(s) of each subject prior to study entry. Number of Subjects: MMR_V Planned, N Randomized, N (Total Vaccinated Cohort) Completed, n (%) 397 (97.5) 396 (97.1) 397 (96.8) 204 (95.8) Total Number Subjects Withdrawn, n (%) 10 (2.5) 12 (2.9) 13 (3.2) 9 (4.2) Withdrawn due to Adverse Events, n (%) 1 (0.2) 1 (0.2) 3 (0.7) 2 (0.9) Withdrawn due to Lack of Efficacy, n (%) Not applicable Not applicable Not applicable Not applicable Withdrawn for other reasons, n (%) 9 (2.2) 11 (2.7) 10 (2.4) 7 (3.3) Demographics MMR_V N (Total Vaccinated Cohort) Females: Males 198: : : :108 Mean Age, months (SD) 14.0 (2.27) 14.1 (2.37) 13.9 (2.17) 14.3 (2.40) White/Caucasian, n (%) 401 (98.5) 405 (99.3) 407 (99.3) 208 (97.7) Primary Efficacy Results: Seroconversion rates and GMTs for anti-mumps antibodies (neutralization assay) for initially seronegative subjects (ATP Cohort for immunogenicity) 28 ED50* GMT PI(D42)* PII(D84) PI(D42)* PII(D84) PI(D42)* PII(D84)

3 MMR_V PI(D42)* PII(D84) n(%) = number(percentage) of subjects with titer specified cut-off = 95% confidence interval; LL = Lower Limit, UL = Upper Limit *Primary Outcome/Efficacy variable Seroconversion rates and GMTs for anti-mumps antibodies (ELISA) for initially seronegative subjects (ATP Cohort for immunogenicity) 231 U/mL GMT (U/mL) PI(D42) PII(D84) PI(D42) PII(D84) PI(D42) PII(D84) MMR_V PI(D42) PII(D84) n(%) = number(percentage) of subjects with titer specified cut-off = 95% confidence interval; LL = Lower Limit, UL = Upper Limit Seroconversion rates and GMTs for anti-measles antibodies for initially seronegative subjects (ATP Cohort for immunogenicity) 150 miu/ml GMT (miu/ml) PI(D42) PII(D84) PI(D42) PII(D84) PI(D42) PII(D84) MMR_V PI(D42) PII(D84) n(%) = number(percentage) of subjects with titer specified cut-off = 95% confidence interval; LL = Lower Limit, UL = Upper Limit Seropositivity rates and GMTs for anti-rubella antibodies for initially seronegative subjects (ATP Cohort for immunogenicity) 4 IU/mL GMT (IU/mL) PI(D42) PII(D84) PI(D42) PII(D84)

4 PI(D42) PII(D84) MMR_V PI(D42) PII(D84) n(%) = number(percentage) of subjects with titer specified cut-off = 95% confidence interval; LL = Lower Limit, UL = Upper Limit Seropositivity rates and GMTs for anti-varicella antibodies for initially seronegative subjects (ATP Cohort for immunogenicity) 1:4 GMT PI(D42) PII(D84) PI(D42) PII(D84) PI(D42) PII(D84) MMR_V PI(D42) PII(D84) n(%) = number(percentage) of subjects with titer specified cut-off = 95% confidence interval; LL = Lower Limit, UL = Upper Limit Incidence of solicited local symptoms reported during the 4-day (Day 0-3) post-vaccination period following each dose (Total Vaccinated Cohort) Symptom Intensity N=407 N=408 Pain Any Grade Redness Any > 20 mm Swelling Any > 20 mm N=401 N=404 Pain Any Redness Any > 20 mm Swelling Any > 20 mm MMR _V N=410 N=213 Pain Any Grade

5 Redness Any > 20 mm Swelling Any > 20 mm N=400 N=207 Pain Any Grade Redness Any > 20 mm Swelling Any > 20 mm N= number of subjects with an administered dose n(%)= number(percentage) of subjects for whom the symptom was reported at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any= any solicited local symptom irrespective of intensity grade Grade 3 pain = Cried when limb was moved/spontaneously painful Incidence of solicited general symptoms reported during the 43-day (Day 0-42) post-vaccination period following each dose (Total Vaccinated Cohort) Symptom Intensity/ relationship N=407 N= C > 39.5C Related Rash Any Grade Related Meningism N=401 N= C > 39.5C Related Rash Any Grade Related Meningism Any

6 MMR_V N=410 N= C > 39.5C Related Rash Any Grade Related Meningism Any Grade N=400 N= C > 39.5C Related Rash Any Grade Related Meningism N= number of subjects with an administered dose n(%)= number(percentage) of subjects for whom the symptom was reported at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any: any solicited general symptom irrespective of intensity grade or relationship to vaccination Grade 3 Parotid/Salivary gland swelling: swelling with accompanying general symptoms Grade 3 Meningism: symptom that prevented normal, everyday activities Grade 3 rash: >150 lesions Related: symptoms considered by the investigator to have a causal relationship to vaccination Safety Results: Number (%) of subjects with unsolicited adverse events after the first dose (Total Vaccinated Cohort) Most frequent adverse events - On-Therapy (occurring within Day 0-42 following vaccination) N = 407 N = 408 N = 410 MMR_V N = 213 Subjects with any AE(s), n (%) 188 (46.2) 188 (46.1) 204 (49.8) 79 (37.1) Subjects with severe AE(s), n (%) 24 (5.9) 22 (5.4) 30 (7.3) 6 (2.8) Subjects with related AE(s), n (%) 33 (8.1) 25 (6.1) 31 (7.6) 7 (3.3) Teething 30 (7.4) 30 (7.4) 33 (8.0) 12 (5.6) Rhinitis 24 (5.9) 24 (5.9) 33 (8.0) 18 (8.5) Upper respiratory tract infection 20 (4.9) 23 (5.6) 19 (4.6) 9 (4.2) Diarrhea 23 (5.7) 17 (4.2) 20 (4.9) 5 (2.3) Cough 20 (4.9) 15 (3.7) 19 (4.6) 10 (4.7) Irritability 25 (6.1) 12 (2.9) 19 (4.6) 5 (2.3) Otitis media 15 (3.7) 14 (3.4) 20 (4.9) 2 (0.9) Pharyngitis 11 (2.7) 10 (2.5) 16 (3.9) 7 (3.3) Safety Results: Number (%) of subjects with unsolicited adverse events after the second dose (Total Vaccinated Cohort)

7 Most frequent adverse events - On-Therapy (occurring within Day 0-42 following vaccination) N = 401 N = 404 N = 400 MMR_V N = 207 Subjects with any AE(s), n (%) 154 (38.4) 140 (34.7) 142 (35.5) 71 (34.3) Subjects with Grade 3 AE(s), n (%) 19 (4.7) 8 (2.0) 12 (3.0) 15 (7.2) Subjects with related AE(s), n (%) 10 (2.5) 8 (2.0) 13 (3.3) 2 (1.0) Rhinitis 35 (8.7) 31 (7.7) 27 (6.8) 23 (11.1) Upper respiratory tract infection 23 (5.7) 22 (5.4) 20 (5.0) 11 (5.3) Teething 15 (3.7) 13 (3.2) 20 (5.0) 6 (2.9) Cough 16 (4.0) 13 (3.2) 14 (3.5) 9 (4.3) Diarrhea 12 (3.0) 10 (2.5) 12 (3.0) 3 (1.4) Irritability 7 (1.7) 9 (2.2) 14 (3.5) 4 (1.9) Bronchitis 6 (1.5) 8 (2.0) 7 (1.8) 8 (3.9) Safety Results: Number (%) of subjects with Serious Adverse Events (SAEs) during the entire study period (Total Vaccinated Cohort) Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs N = 407 N = 408 N = 410 MMR_V N = 213 Subjects with any SAE(s), n (%) [n related] 3 (0.7) [0] 4 (1.0) [1] 6 (1.5) [1] 3 (1.4) [0] Gastroenteritis 1 (0.2) [0] 1 (0.2) [0] 0 (0.0) [0] 1 (0.5) [0] Pneumonia 0 (0.0) [0] 0 (0.0) [0] 2 (0.5) [0] 0 (0.0) [0] Animal bite 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] Bacterial infection 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.5) [0] Conjunctivitis 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] Contusion 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] Croup infectious 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.5) [0] Drug toxicity 0 (0.0) [0] 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] Febrile convulsion 0 (0.0) [0] 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] Hypersensitivity 0 (0.0) [0] 1 (0.2) [1] 0 (0.0) [0] 0 (0.0) [0] Otitis media 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Pharyngitis 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.5) [0] Pharyngotonsillitis 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Pyelonephritis 1 (0.2) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Pyrexia 0 (0.0) [0] 0 (0.0) [0] 1 (0.2) [1] 0 (0.0) [0] Viral upper respiratory tract infection 0 (0.0) [0] 0 (0.0) [0] 1 (0.2) [0] 0 (0.0) [0] Fatal SAEs N = 407 N = 408 N = 410 MMR_V N = 213 Subjects with fatal SAE(s), n (%) [n related] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Conclusion: Six weeks after, at least 92.8% of subjects had anti-mumps titers cut-off s by neutralization test. At the same time point, at least 95.3%, 99.7% and 95.7% of subjects had anti-measles, anti-rubella and anti-varicella antibody titers cut-off s. Six weeks after, at least 99.4% of subjects had anti-mumps titers cut-off s by neutralization test. At the same time point, at least 98.4% and 97.3% of subjects had anti-measles and anti-varicella antibody titers cut-off s, while all subjects had anti-rubella antibody titers cut-off s. Across doses and groups, redness and fever were the most frequently reported solicited local and general symptoms, respectively. SAEs were reported in 3 (0.7%), 4 (1.0%), 6 (1.5%) and 3 (1.4%) subjects in the,, and MMR_V groups, respectively; 2 of these SAEs, 1 in the group and 1 in the group, were considered by the investigators to be related with the study vaccination. No fatal SAEs were reported during the course of the study. Date updated: 19-December-2016