Consistency Study of GlaxoSmithKline (GSK) Biologicals' MMR Vaccine (209762) (Priorix) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine (M-M-R II), in Children 12 to 15 Months of Age

Measles Clinical Trial

Official title:

Consistency Study of GSK Biologicals' Measles-mumps-rubella (MMR) Vaccine (209762) (Priorix) Comparing Immunogenicity and Safety to Merck & Co., Inc.'s MMR Vaccine (M-M-R II), in Healthy Children 12 to 15 Months of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702428
• Other study ID #: 115648
• Secondary ID: 2011-004891-12
• Status: Completed
• Phase: Phase 3
• Start date: November 9, 2012
• Est. completion date: April 16, 2015

Study information

• Verified date: November 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate consistency in terms of the immune response to three different lots of GSK Biologicals' trivalent MMR vaccine manufactured to target potencies, and compare its immunogenicity to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).

Description:

This study will evaluate the consistency of the immune response to three different lots of GSK Biologicals' trivalent investigational MMR vaccine (referred to as INV_MMR vaccine, throughout this document) and compare its immunogenicity to the US standard of care comparator vaccine (M-M-R II, Merck and Co., Inc., referred to as COM_MMR throughout this document) in children during their second year of life. The INV_MMR vaccine will be given as one of three consistency lots manufactured to target potencies designated as INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3. The COM_MMR vaccine will be given as one of two lots designated COM_MMR_L1 and COM_MMR_L2 and will be analysed as pooled lots within the study. The MMR vaccine will be co-administered with Varivax (VV), Havrix (HAV) and (in the US sub-cohort only) Prevnar 13 (PCV-13) which are routinely administered to children of this age in the US.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5016
• Est. completion date: April 16, 2015
• Est. primary completion date: November 25, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 15 Months

Eligibility

Inclusion Criteria:

• Male or female child between 12 and 15 months of age at the time of vaccination.

• The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, can, and will comply with the requirements of the protocol.

• Written informed consent obtained from the parent(s)/LAR(s) of the child.

• Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history.

For US children only:

• Child that previously received a 3-dose series of Prevnar 13 only (i.e., no doses given as Prevnar/Prevenar), with the last dose at least 60 days prior to study entry.

Exclusion Criteria:

• Child in care.

• Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Day 0) or planned use during the entire study period.

• Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product.

• Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study.

• For corticosteroids, this will mean prednisone, =0.5 mg/kg/day or equivalent.

• Inhaled and topical steroids are allowed.

• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1 and ending at Visit 2. Please Note:

• Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s).

• Any other age appropriate vaccine may be given starting at Visit 2 and anytime thereafter.

• Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2.

• History of measles, mumps, rubella, varicella/zoster and/or hepatitis A disease.

• Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting within 30 days prior to first study vaccination.

• Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• A family history of congenital or hereditary immunodeficiency.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin.

• Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.

• Acute disease at the time of enrollment. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.

• Active untreated tuberculosis based on medical history.

• Any other condition which, in the opinion of the investigator, prevents the child from participating in the study.

For US children only:

• Child that previously received a vaccination with heptavalent Prevnar/Prevenar (prior vaccination should be with 3 doses of Prevnar 13 only).

• Child that previously received a fourth dose of any pneumococcal conjugate vaccine.

Related Conditions & MeSH terms

• Measles
• Mumps
• Rubella

Intervention

Biological:
• Priorix
Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.
• M-M-R II
Subjects receive 1 dose of MMR vaccine which is administered subcutaneously in the triceps region of the left arm.
• Varivax
Subjects receive 1 dose of VV vaccine which is administered subcutaneously in the triceps region of the right arm.
• Havrix
Subjects receive 1 dose of HAV vaccine which is administered intramuscularly in the anterolateral region of the right thigh.
• Prevnar 13
US subjects receive 1 dose of PCV-13 vaccine which is administered intramuscularly in the anterolateral region of the left thigh.

Locations

Country	Name	City	State
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
Finland	GSK Investigational Site	Espoo
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Jarvenpaa
Finland	GSK Investigational Site	Kokkola
Finland	GSK Investigational Site	Oulu
Finland	GSK Investigational Site	Pori
Finland	GSK Investigational Site	Seinajoki
Finland	GSK Investigational Site	Tampere
Finland	GSK Investigational Site	Turku
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Mexico
Puerto Rico	GSK Investigational Site	San Juan
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	L'Eliana, Valencia
Spain	GSK Investigational Site	Quart De Poblet, Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
United States	GSK Investigational Site	Ames	Iowa
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Augusta	Kansas
United States	GSK Investigational Site	Barnwell	South Carolina
United States	GSK Investigational Site	Bossier City	Louisiana
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Charlottesville	Virginia
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Daly City	California
United States	GSK Investigational Site	Dothan	Alabama
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Evergreen Park	Illinois
United States	GSK Investigational Site	Fall River	Massachusetts
United States	GSK Investigational Site	Falls Church	Virginia
United States	GSK Investigational Site	Fayetteville	Arkansas
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hayward	California
United States	GSK Investigational Site	Hermitage	Pennsylvania
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Ithaca	New York
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Layton	Utah
United States	GSK Investigational Site	League City	Texas
United States	GSK Investigational Site	Los Gatos	California
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	Marshfield	Wisconsin
United States	GSK Investigational Site	Mission Hills	California
United States	GSK Investigational Site	Nampa	Idaho
United States	GSK Investigational Site	Niles	Michigan
United States	GSK Investigational Site	Overland Park	Kansas
United States	GSK Investigational Site	Paramount	California
United States	GSK Investigational Site	Payson	Utah
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pleasanton	California
United States	GSK Investigational Site	Provo	Utah
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Roy	Utah
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint George	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Santa Clara	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Sellersville	Pennsylvania
United States	GSK Investigational Site	Stevensville	Michigan
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Syracuse	Utah
United States	GSK Investigational Site	Tomball	Texas
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	Warwick	Rhode Island
United States	GSK Investigational Site	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Estonia,  Finland,  Mexico,  Puerto Rico,  Spain, 

References & Publications (1)

Klein NP, Abu-Elyazeed R, Povey M, Macias Parra M, Diez-Domingo J, Ahonen A, Korhonen T, Tinoco JC, Weiner L, Marshall GS, Silas PE, Sarpong KO, Ramsey KP, Fling JA, Speicher D, Campos M, Munjal I, Peltier C, Vesikari T, Baccarini C, Caplanusi A, Gillard P, Carryn S, Henry O. Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study. J Pediatric Infect Dis Soc. 2019 Mar 8. pii: piz010. doi: 10.1093/jpids/piz010. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	Seroresponse was defined as post-vaccination anti-measles virus antibody concentration =200 milli International Unit/Milliliter (mIU/mL) among subjects who were seronegative (antibody concentration <150 mIU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Anti-measles Virus Antibody Concentrations	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value	Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration =10 ELISA Unit/Milliliter (EU/mL) among subjects who were seronegative (antibody concentrations <5 EU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Anti-mumps Virus Antibody Concentration	Antibody concentrations were expressed as GMCs in EU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value	Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration =10 International Unit/Milliliter (IU/mL) among subjects who were seronegative (antibody concentrations <4 IU/mL) before vaccination. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Anti-rubella Virus Antibody Concentration	Antibody concentrations were expressed as GMCs in IU/mL. This outcome measure is applicable to reporting groups INV_MMR_L1, INV_MMR_L2 and INV_MMR_L3 as analysis was performed on subjects who received one of the lots of INV_MMR vaccine.	At Day 42
Primary	Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Seroresponse was defined as post-vaccination anti-measles virus antibody concentration =200 mIU/mL among subjects who were seronegative (antibody concentration <150 mIU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV_MMR in terms of seroresponse rates to measles virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV_MMR lots is =90% for antibodies to measles virus.	At Day 42
Primary	Anti-measles Virus Antibody Concentrations in Pooled MMR Groups	Antibody concentrations were expressed as GMCs in mIU/mL.	At Day 42
Primary	Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration =10 EU/mL among subjects who were seronegative (antibody concentrations <5 EU/mL) before vaccination.	At Day 42
Primary	Anti-mumps Virus Antibody Concentration in Pooled MMR Groups	Antibody concentrations were expressed as GMCs in EU/mL.	At Day 42
Primary	Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value in Pooled MMR Groups	Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration =10 IU/mL among subjects who were seronegative (antibody concentrations <4 IU/mL) before vaccination. Criteria to demonstrate an acceptable immune response for INV_MMR in terms of seroresponse rates to rubella virus at Day 42: The LL of 2-sided 95% CI for the seroresponse rate for the pooled INV_MMR lots is =90% for antibodies to rubella virus.	At Day 42
Primary	Anti-rubella Virus Antibody Concentration in Pooled MMR Groups	Antibody concentrations were expressed as GMCs in IU/mL.	At Day 42
Secondary	Percentage of Subjects With an Anti-Varicella Zoster Virus (VZV) Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups	Seroresponse was defined as post-vaccination anti-VZV antibody concentration =75 mIU/mL among subjects who were seronegative (antibody concentration <25 mIU/mL) before vaccination.	At Day 42
Secondary	Anti-VZV Virus Antibody Concentration in US Sub-cohort of Pooled MMR Groups	Antibody concentrations were expressed as GMCs in mIU/mL.	At Day 42
Secondary	Percentage of Subjects With an Anti-HAV Antibody Concentration Equal to or Above the Cut-off Value in US Sub-cohort of Pooled MMR Groups	Percentage of subjects with an Anti-HAV antibody concentration equal to or above 15 mIU/mL were reported.	At Day 42
Secondary	Anti-HAV Antibody Concentrations in US Sub-cohort of Pooled MMR Groups	Antibody concentrations were expressed as GMCs in mIU/mL.	At Day 42
Secondary	Anti-S.Pneumoniae Antibody Concentration in US Sub-cohort of Pooled MMR Groups	Antibody concentrations were expressed as GMCs in microgram/Milliliter (µg/mL).	At Day 42
Secondary	Number of Subjects With Any Solicited Local Adverse Events (AEs)	Assessed solicited local AEs were pain, redness and swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 4-days (Days 0-3) post-vaccination period
Secondary	Number of Subjects With Any Solicited General AEs	Assessed solicited general AEs were drowsiness, irritability and loss of appetite. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 15-days (Days 0-14) post-vaccination period
Secondary	Number of Subjects Reporting Any Fever	Any fever = Fever = 38°C.	During the 43-days (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting Any Rash	Assessed were any localized or generalized rash, rash with fever, varicella-like rash, measles/rubella-like rash. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 43-days (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting Any MMR Specific Solicited AEs	Assessed MMR specific solicited AEs were any suspected signs of meningism including febrile convulsions and parotid/salivary gland swelling. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 43-days (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting Any Unsolicited AEs	Unsolicited adverse event (AE) was defined as any adverse event reported in addition to those solicited during the clinical study and also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of the symptom regardless of intensity grade or relation to vaccination.	During the 43-days (Days 0-42) post-vaccination period
Secondary	Number of Subjects Reporting AEs of Specific Interest	AEs of specific interest included new onset chronic disease (NOCD) (e.g., autoimmune disorders, asthma, type I diabetes, vasculitis, celiac disease, conditions associated with sub-acute or chronic thrombocytopenia and allergies) and AEs prompting emergency room (ER) visits.	From Day 0 through the end of study (Day 180)
Secondary	Number of Subjects Reporting Any Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity. Any SAE = Occurrence of SAE regardless of intensity grade or relation to vaccination.	From Day 0 through the end of study (Day 180)