GSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives:

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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: GlaxoSmithKline (GSK) Biologicals live attenuated Measles, Mumps, Rubella vaccine (MMR) Vaccine Study Number: (MMR-159) Title: Immunogenicity and safety study of GSK Biologicals combined measles-mumps-rubella vaccine in subjects seven years and older (209762). Priorix (INV_MMR): GlaxoSmithKline (GSK) Biologicals live attenuated Measles, Mumps, Rubella vaccine (MMR) Vaccine. Rationale: The purpose of this study was to support licensure of GSK Biologicals' trivalent combined Measles, Mumps And Rubella vaccine (INV_MMR vaccine) in the US by generating immunogenicity and safety data in subjects 7 years of age and older. This study evaluated the immunogenicity of INV_MMR vaccine in comparison to the US standard of care (COM_MMR) when both were used as a second dose in subjects 7 years of age and older. The comparator Com_MMR vaccine used in this study consisted of two lots of MMR II designated Com_MMR_L1 and Com_MMR_L2. Throughout this study, endpoints for the lots of comparator Com_MMR vaccine (Com_MMR_L1 and Com_MMR_L2) were analyzed as pooled lots. The comparator Com_MMR vaccine used consisted of two lots of MMR II designated Com_MMR_L1 and Com_MMR_L2 and was analyzed as pooled lots. M-M-R II (COM_MMR): Merck & Co., Inc. s Measles, Mumps and Rubella virus vaccine live Phase: IIIA Study Period: 17 July 2014 to 17 September 2015 Study Design: Observer-blind, randomized (2:1:1), controlled, multicentre, multi-country, consistency study with three parallel groups. Centres: 17 centres in 3 countries: Estonia, Slovakia, and the United States (US) Indication: Active immunization against measles, mumps and rubella diseases of healthy subjects, 7 years of age and older. Treatment: The study groups were as follows: : Subjects received one dose of INV_MMR vaccine at Visit 1 (Day 0). : Subjects received one dose of COM_MMR vaccine at Visit 1 (Day 0). o COM_MMR_L1 Group: Subjects received one dose of COM_MMR vaccine from Lot 1. o COM_MMR_L2 Group: Subjects received one dose of COM_MMR vaccine from Lot 2. The two lots of comparator vaccine were analyzed as pooled lots. All vaccines were administered subcutaneously in the triceps of the upper arm (preferably left side) Objectives: To demonstrate the non-inferiority of INV_MMR vaccine to COM_MMR vaccine in terms of Geometric Mean Concentration (GMCs) for anti measles, anti mumps and anti rubella antibodies at Day 42. Criteria for the determination of non-inferiority for measles, mumps, and rubella viruses: Lower limit (LL) of the 2- sided 95% Confidence Interval (CI) on GMC ratio (INV_MMR over COM_MMR) is equal to or above 0.67 for antimeasles, anti-mumps, and anti rubella antibodies.

2 Primary Outcome Variable(s): Immunogenicty: Immunogenicity of the study vaccines at Day 42 in terms of antibody concentration Anti-measles virus, anti-mumps virus and anti-rubella virus antibody concentrations at Day 42. Secondary Outcome Variable(s): Immunogenicity Immunogenicity of the study vaccines at Day 42 in terms of seroresponse*. Safety A minimum 4-fold rise in anti-measles, anti-mumps and anti-rubella virus antibody concentration at Day 42. Solicited local and general symptoms: Occurrence of solicited local symptoms (injection site redness, pain and swelling) from Day 0 to Day 3 after vaccination. Occurrence of solicited general symptoms from Day 0 to Day 42 after vaccination in terms of fever (defined as temperature 38 C/100.4 F), rash, parotid/salivary gland swelling, any sign of meningism, and joint pain (arthralgia/arthritis). Unsolicited adverse events (AEs): Pre-specified AEs: Occurrence of unsolicited symptoms from Day 0 to Day 42 after vaccination according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. Occurrence of New Onset Chronic Disease (NOCDs) (e.g. autoimmune disorders, asthma, arthritis /arthralgia, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) from Day 0 through study end. Occurrence of conditions prompting Emergency room (ER) visits from Day 0 through study end. Serious adverse events (SAEs): Occurrence of SAEs from Day 0 through study end. *Seroresponse for MMR was defined as: Anti-measles virus antibody concentration equal to or above the threshold of 200 miu/ml after administration of INV_MMR vaccine vs. COM_MMR at Day 42. Anti-mumps virus antibody concentration equal to or above the threshold of 10 EU/mL after administration of INV_MMR vaccine vs. COM_MMR at Day 42. Anti-rubella virus antibody concentration equal to or above the threshold of 10 IU/mL after administration of INV_MMR vaccine vs. COM_MMR at Day 42. Statistical Methods: 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 for whom immunogenicity data were available and all vaccinated subjects with a documented vaccine administration. The ATP cohort for immunogenicity included all eligible subjects (i.e., subjects who received the study vaccine as per protocol, who had not received a vaccine leading to the exclusion from the ATP cohort in the protocol up to the post-vaccination blood sampling, subjects for whom the administration route of study vaccines is known and correct and for whom the randomization code has not been broken) with post-dose serology results available for at least one antigen of measles, mumps, or rubella, who complied with the procedures and intervals defined in the protocol, who did not meet any elimination criteria up to the Visit 2 (Day 42) blood sample, and who had no intercurrent medical conditions leading to elimination before the post vaccination

3 blood sample. Analysis of Immunogenicity: The analysis was performed on the ATP cohort for immunogenicity. Descriptive analyses for within groups assessment: Percentage of subjects above cut-off and GMCs at Day 0 and Day 42 for anti-measles, anti-mumps and antirubella virus antibodies were summarized with their 95% CIs after vaccination. Fold rise of antibody concentrations from pre-vaccination were tabulated for each antigen in each treatment arm. The percentage of subjects (with their 95% CIs) achieving a 4-fold or greater rise in antibody concentration post-vaccination were reported. Descriptive analyses for between groups assessment: For primary objective, the 2-sided 95% CI for the adjusted GMC ratio (INV_MMR divided by COM_MMR) were calculated for antibodies to measles, mumps and rubella viruses, between groups (INV_MMR over COM_MMR). Analysis of Safety: The analysis was performed on the Total Vaccinated cohort. The percentage of children (with 95% CIs) with at least one local [during the 4 day follow-up period after vaccination (Days 0-3)], general and any AE (solicited and/or unsolicited Days 0-42) were summarized by vaccine group. The same tabulations were performed for grade 3 general and local symptoms. The percentage of children reporting any, related and grade 3 fever during the 43 day (Days 0-42) after vaccination were tabulated. The percentage of subjects with the symptom reported between Days 0-42 after vaccination for rash, parotid gland swelling, and any suspected signs of meningism/ seizure and arthralgia/arthritis were tabulated with its 95% CIs by vaccine group. Similar tabulations were performed for SAEs during the entire study period. Study Population: Healthy male or female children 7 years of age or older at the time of vaccination for whom investigator believed that their parent(s)/legally Acceptable Representatives [LAR(s)] complied with the protocol requirements were enrolled in the study. Written informed consent was obtained from the subject s parent(s)/lar(s). Children with stable health as established by medical history and investigator s clinical examination were enrolled in the study. For all children 7-17 years of age, written documentation of prior receipt of 1 dose of MMR vaccine administered on or after the first birthday was taken. For all adults 18 years of age and older, prior receipt (written or verbal history) of at least one dose of MMR vaccine and US citizen details were collected. Women were to be of non-childbearing potential, or, if of childbearing potential had to practice adequate contraception starting 30 days prior to vaccination until 3 months after receipt of the study vaccination and to have a negative pregnancy test. The subjects with history, known exposure and received previous vaccination against measles, mumps, rubella disease were excluded. Subjects with history of allergic disease or reactions, active untreated tuberculosis and acute disease were also excluded from the study. Number of subjects vaccinated, completed and withdrawn with reason for withdrawal (Total Vaccinated cohort) n % n % Subjects vaccinated Subjects completed Visit 2 (Day 42) Subjects withdrawn by Visit 2 (Day 42) Reasons for withdrawal: Lost to follow-up Others Subject had previously enrolled in this study as subject Subjects completed the last phone contact Subjects withdrawn by the last phone contact Reasons for withdrawal: Consent withdrawal (not due to an adverse event) Lost to follow-up Others Subject is now incarcerated Vaccinated = number of subjects who were vaccinated in the study Completed = number of subjects who completed visit 2

4 Withdrawn = number of subjects who did not come back for the visit 2 Subjects who were vaccinated but did not return for visit 2. Subjects who completed visit 2 but did not participate in the last phone contact. Summary of demographic characteristics (Total Vaccinated cohort) Demographic N = 454 N = 457 Characteristics Parameters or Categories Value or n % Value or n % Age (years) (1) Mean SD Median Minimum Maximum Age categories <18 years years Country categories United States Estonia Slovakia Gender Female Male Geographic African Heritage/African American ancestry American Indian or Alaskan native Asian - Central/South Asian heritage Asian - East Asian heritage Asian - Japanese heritage Asian - South East Asian heritage Native Hawaiian or other Pacific Islander White - Arabic/North African heritage White - Caucasian/European heritage Other N = total number of subjects in each vaccine group or in the ATP cohort for immunogenicity n/% = number/percentage of subjects in a given category Value = value of the considered parameter SD = standard deviation (1) Age was calculated as the number of complete years between a subject's birth date and the date of study vaccination Primary Outcome Results: Adjusted ratios of anti-measles, anti-mumps and anti-rubella geometric mean concentrations at Day 42 between INV_MMR and COM_MMR (ATP cohort for immunogenicity) Adjusted GMC Ratio /COM_MMR Group Adjusted 95% CI Adjusted N GMC LL UL N GMC LL UL Ratio LL UL Anti-measles (miu/ml) Anti-mumps (EU/mL) Anti-rubella (IU/mL) The 95% CI for adjusted geometric mean concentrations (GMCs) and the adjusted GMC ratio were obtained using an ANCOVA model on the logarithm-transformed concentrations including the vaccine group (for adjusted GMC ratio) as fixed effect, gender, age and country groups as continuous effects and the pre-vaccination log-transformed concentration as regressor. N = Number of subjects with both pre and post-vaccination results available LL = lower limit, UL = upper limit Secondary Outcome Results: Difference of anti-measles, anti-mumps and anti-rubella seroresponse rates at Day 42

5 between INV_MMR and COM_MMR (ATP cohort for immunogenicity) Difference in Percentage (INV_MMR Minus COM_MMR) Difference 95% CI N n % N n % N n % Anti-measles ( 200 miu/ml) Anti-mumps ( 10 EU/mL) Anti-rubella ( 10 IU/mL) N = number of subjects with available results n/% = number/percentage of subjects with concentration within the specified range 95% CI = Two-sided 95% confidence interval using the Miettinen & Nurminen method; LL = lower limit, UL = upper limit Secondary Outcome Results: Number (%) of subjects above cut-off and GMCs at Day 0 and Day 42 for anti-measles virus antibodies (ATP cohort for immunogenicity) 150 miu/ml 200 miu/ml GMC (miu/ml)* Vaccine 95% CI (1) 95% CI (1) 95% CI (2) Group Time Point N Value LL UL INV_MMR Day Day COM_MMR Day Day Seronegative=anti-measles virus antibody concentration < the assay cut-off value (150 miu/ml) GMC=geometric mean antibody concentration calculated on all subjects N=number of subjects with available results n/%=number/percentage of subjects with concentration within the specified range (1) 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit (2) 95% CI=Exponential-transformation of the 95% CI for the mean of log-transformed concentration The GMC and associated CI are not reliable when the majority of subjects in the sub-group at the time point have concentrations below the assay cut-off *Primary outcome measure Secondary Outcome Results: Number (%) of subjects above cut-off and GMCs at Day 0 and Day 42 for anti-mumps virus antibodies (ATP cohort for immunogenicity) Vaccine Group 5 EU/mL 10 EU/mL GMC (EU/mL)* 95% CI (1) 95% CI (1) 95% CI (2) Time Point N Value LL UL INV_MMR Day Day COM_MMR Day Day Seronegative=anti-mumps virus antibody concentration < the assay cut-off value (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 concentration within the specified range (1)95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit (2)95% CI=Exponential-transformation of the 95% CI for the mean of log-transformed concentration The GMC and associated CI are not reliable when the majority of subjects in the sub-group at the time point have concentrations below the assay cut-off *Primary outcome measure Secondary Outcome Results: Number (%) of subjects above cut-off and GMCs at Day 0 and Day 42 for anti-rubella virus antibodies (ATP cohort for immunogenicity) Vaccine Group 4 IU/mL 10 IU/mL GMC (IU/mL)* 95% CI (1) 95% CI (1) 95% CI (2) Time Point N Value LL UL INV_MMR Day Day COM_MMR Day Day

6 Seronegative=anti-rubella virus antibody concentration < the assay cut-off value (4 IU/mL) GMC=geometric mean antibody concentration calculated on all subjects N=number of subjects with available results n/%=number/percentage of subjects with concentration within the specified range (1)95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit (2)95% CI=Exponential-transformation of the 95% CI for the mean of log-transformed concentration The GMC and associated CI are not reliable when the majority of subjects in the sub-group at the time point have concentrations below the assay cut-off *Primary outcome measure Secondary Outcome Results: Number (%) of subjects who achieved a 4-fold or greater rise in anti-measles, antimumps and anti-rubella virus antibody concentrations at Day 42 (ATP cohort for immunogenicity) N n % LL UL N n % LL UL Anti-measles Anti-mumps Anti-rubella N= number of subjects with both pre- and post-vaccination available results n/%= number/percentage of subjects who achieved a 4-fold or greater rise from pre-vaccination in anti-measles, antimumps and anti-rubella virus antibody concentrations at Day 42 For subjects with seronegative status at pre-vaccination, a 4-fold rise in antibody concentration is defined as 4 times the cut-off level of the assay. Cut-off levels for anti-measles, anti-mumps and anti-rubella virus antibody concentrations are 150 miu/ml, 5 EU/mL and 4 IU/mL. 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit Secondary Outcome Results: Number (%) of solicited local symptoms reported during the 4-day (Days 0-3) post-vaccination period (Total vaccinated cohort) Symptom Intensity N = 433 Injection site redness Any >50mm Injection site swelling Any >50mm Injection site pain Any Grade N=number of subjects with the documented dose with local symptoms sheets completed 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL= lower limit, UL=upper limit Any= Occurence of any local symptom regardless of their intensity grade Grade3 pain= Significant pain at rest. Prevented normal every day activities. Secondary Outcome Results: Number (%) of fever per half degree increment during the 43-day (Days 0-42) postvaccination period (Total vaccinated cohort) Fever ( C) N = 431 Intensity/Relationship 38 C >39.5 C > Related N=number of subjects with the documented dose with general symptoms sheets completed 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL= lower limit, UL = upper limit Related=symptom assessed by the investigator as causally related to study vaccination Secondary Outcome Results: Number (%) of subjects reporting solicited joint pain (arthralgia/arthritis) during the 43- day (Days 0-42) post-vaccination period (Total vaccinated cohort)

7 N = 431 Intensity/Relationship Any Grade Related N=number of subjects with the documented dose with general symptoms sheets completed 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination Grade3 joint pain (arthralgia/arthritis)= Pain which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy). Related = symptom assessed by the investigator as causally related to study vaccination. Secondary Outcome Results: Number (%) of subjects reporting solicited rash or exanthem the 43-day (Days 0-42) post-vaccination period (Total vaccinated cohort) N = 431 Intensity/Relationship Any Grade Related Localized rash Generalized rash Rash type - measles/rubella-rash Rash type - others INV_MMR=Investigational MMR vaccine; COM_MMR=Comparator MMR vaccine N=number of subjects with the documented dose with general symptoms sheets completed 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method;ll=lower limit,ul=upper limit Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination Grade3 rash/exanthema= Rash which prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy.) Related = symptom assessed by the investigator as causally related to study vaccination MA=medically attended visit, resulting in any hospital, emergency room visit or a visit to the doctor s office Secondary Outcome Results: Number (%) of subjects reporting solicited parotid/salivary gland swelling; during the 43 day (Days 0-42) post-vaccination period (Total vaccinated cohort) N = 431 Intensity/Relationship Any Grade Related N=number of subjects with the documented dose with general symptoms sheets completed 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL=lower limit, UL=upper limit Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination Grade3 parotid/salivary gland swelling= Swelling that accompanied general symptoms Related = symptom assessed by the investigator as causally related to study vaccination Secondary Outcome Results: Number (%) of subjects reporting solicited signs of meningism/seizure during the 43 day (Days 0-42) post-vaccination period (Total vaccinated cohort) Intensity/Relationship N = 431

8 Any Grade Related N=number of subjects with the documented dose with general symptoms sheets completed 95% CI=Two-sided 95% confidence interval using the Clopper Pearson method; LL= lower limit,ul = upper limit Any= occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination Grade3 meningism/seizure= Prevented normal, everyday activities (In adults/adolescents, such an AE could, for example, prevented attendance at work/school and could necessitated the administration of corrective therapy.) Related = symptom assessed by the investigator as causally related to study vaccination Secondary Outcome Results: Number (%) of subjects with unsolicited AEs classified by MedDRA Primary System Organ Class and Preferred Term reported during the 43-day (Days 0-42) post-vaccination period (Total vaccinated cohort) AEs On-Therapy (Occurring within days 0-42 following vaccination) N = 454 N = 457 Subjects with Any AEs At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term) N = number of subjects with the administered dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL = lower limit, UL = upper limit Secondary Outcome Results: Number (%) of subjects who reported the occurrence of NOCD classified by MedDRA Primary System Organ Class and Preferred Term from Day 0 up to the end of study post-vaccination period (Total vaccinated cohort) NOCDs On-Therapy (Occurring during the entire study period following vaccination) N = 454 N = 457 Subjects with Any NOCDs At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term) N = number of subjects with the administered dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL = lower limit, UL = upper limit Secondary Outcome Results: Number (%) of subjects who reported the occurrence of conditions prompting ER visits classified by MedDRA Primary System Organ Class and Preferred Term from Day 0 up to the end of study postvaccination period (Total vaccinated cohort) ER visits On-Therapy (during the entire study period following vaccination) N = 454 N = 457 Subjects with any ER visits MedDRA version 18.1 At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term) N = number of subjects with the administered dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL = lower limit, UL = upper limit Safety Results: Solicited and unsolicited symptoms experienced by at least 5% of subjects, classified by MedDRA Primary System Organ Class and Preferred Term within the 43-day (Days 0-42) post vaccination period, including number of events reported SAE excluded (Total vaccinated cohort)

9 (N = 433) (N = 446) Primary System Preferred Term 95% CI % 95% CI Organ Class (Code) (Code) n* n % LL UL n* n LL UL At least one symptom General disorders and administration site Injection site erythema conditions ( ) ( ) Injection site swelling ( ) Pyrexia ( ) Vaccination site pain ( ) MedDRA version: 18.1 At least one symptom = number of subjects in the population with at least one symptom experienced (regardless of the MedDRA Preferred Term) N = number of subjects with the administered dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = Two-sided 95% confidence interval using the Clopper Pearson method; LL = lower limit, UL = upper limit Safety Results: Number (%) of subjects with serious adverse events during the study period including number of events reported (Total vaccinated cohort) Type of Event Primary System Organ Class Preferred Term (CODE) N = 454 N = 457 n* n % n* n % SAE At least one symptom Gastrointestinal disorders Abdominal pain ( ) ( ) Abdominal pain lower ( ) Pancreatitis relapsing ( ) Hepatobiliary disorders Biliary colic ( ) ( ) Infections and infestations Pyelonephritis ( ) ( ) Injury, poisoning and Jaw fracture ( ) procedural complications Tendon injury ( ) ( ) Neoplasms benign, malignant and unspecified (incl cysts and polyps) ( ) Breast cancer ( ) Pregnancy, puerperium and perinatal conditions ( ) Abortion spontaneous ( ) Psychiatric disorders ( ) Psychogenic seizure ( ) Related SAE At least one symptom Fatal SAE At least one symptom Related Fatal At least one symptom SAE

10 At least one symptom = at least one symptom experienced (regardless of the MedDRA Preferred Term) N = number of subjects with the administered dose n* = number of events reported n/% = number/percentage of subjects reporting the symptom at least once Conclusion: The primary objective to demonstrate the non-inferiority of INV_MMR vaccine to COM_MMR vaccine in terms of geometric mean concentrations (GMCs) for anti measles, anti mumps and anti rubella antibodies at Day 42 was met because the lower limit of the 2 sided 95% confidence interval (CI) on GMC ratio (INV_MMR over COM_MMR) is equal to or above 0.67 for antibodies to measles, mumps and rubella viruses. The GMC of the anti-measles virus antibodies at Day 42 for and was miu/ml and miu/ml, respectively. The GMC of the anti-mumps virus antibodies at Day 42 for and was EU/mL and EU/mL, respectively. The GMC of the anti-rubella virus antibodies at Day 42 for and was 75.3 IU/mL and 75.6 IU/mL, respectively. No SAEs were assessed by the investigators as causally related to the study vaccination. No fatal SAEs were reported during the entire study. Date updated: 12-October-2016