Coadministration of Measles-rubella and Rotavirus Vaccines

Phase 4

Completed

Conditions: Rotavirus Geometric Mean Titer (GMT)
Measles Antibody Seroconversion
Rotavirus Immunoglobulin A (IgA) Seropositivity
Rubella Antibody Seroconversion

Interventions: Biological: Rotarix vaccine
Biological: measles-rubella vaccine

Registration Number: NCT01700621

Lead Sponsor: PATH

Brief Summary: The investigators aim to establish the non-inferiority of concomitant administration of measles-rubella and rotavirus vaccines to measles-rubella vaccine given alone in terms of measles seroconversion rates. The primary study hypothesis is the measles seroconversion rate as defined by the percentage of children seroconverting to measles with a measles serum antibody concentration of \>=1:120 at 8 weeks post vaccination after the concomitant administration of measles-rubella and rotavirus vaccines is non-inferior to that obtained when measles-rubella vaccine is given alone in children 9 months of age who have received a primary rotavirus vaccine series with the first dose between 6 and 10 weeks and the second at least 4 weeks later and are seronegative for measles antibody in the pre-vaccination sample.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 482

Inclusion Criteria

Child 9 months of age eligible for measles-rubella vaccination
documented evidence of a primary rotavirus vaccine series with first dose between 6 and 10 weeks of age and second dose at least 4 weeks after first dose
healthy infants free of chronic or serious medical condition as determined by history and physical examination at time of study enrollment
parents/guardians of each participant are able to understand and follow study procedures and agree to participate in study by providing signed informed consent

Exclusion Criteria

hypersensitivity to any component of measles-rubella or Rotarix vaccine which would preclude administration of the vaccine
history of intussusception, intestinal malformations, or abdominal surgery
known history of measles and/or rubella disease
history of previous receipt of measles and/or rubella vaccine
use of any immunosuppressive drugs or immunoglobulin and/or blood products since birth or anticipated during study period
current enrolment in any other intervention trial or use of any investigational drug or vaccine throughout the study period
any participant who reports planning to leave the study area before the completion of the study
acute diarrhea (defined as ≥3 loose stools within a 24-hour period) or vomiting (defined as projectile vomiting or any vomiting at the discretion of the clinician) at the time of enrollment or within the last 24 hours
acute febrile illness (defined as a temperature of ≥38°C) at the time of enrollment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
measles-rubella and rotavirus vaccines	measles-rubella vaccine	receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine and one 1.0 ml dose of oral Rotarix vaccine at 9 months of age
measles-rubella and rotavirus vaccines	Rotarix vaccine	receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine and one 1.0 ml dose of oral Rotarix vaccine at 9 months of age
measles-rubella vaccine	measles-rubella vaccine	receive one 0.5 ml subcutaneous dose of live attenuated measles-rubella vaccine at 9 months of age

Primary Outcome Measures

Name	Time	Method
Percentage/Number of Subjects With Seroprotection for Measles Virus Serum Neutralization Antibodies	8 weeks post vaccination	Detected by plaque reduction neutralization test (PRNT). Seroprotection defined as measles serum antibody concentration \>=1:120 8 weeks post vaccination. Assays were standardized using WHO Second International Standard for measles antibody containing 5000 mIU/ml, which enables the 50% neutralizing antibody end-point dose (titer, ND50) of test samples to be transformed to antibody concentrations in terms of mIU/ml. The analytical cut-off value in this assay was ND50 \< 1/8; this was the lowest dilution at which sera were tested.
Percentage/Number of Subjects With Seroprotection for Anti-measles Virus Immunoglobulin G (IgG)	8 weeks post vaccination	Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for measles virus. All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).

Secondary Outcome Measures

Name	Time	Method
Percentage/Number of Subjects With Seroconversion for Anti-rubella Virus Immunoglobulin G (IgG)	8 weeks post vaccination	Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Geometric Mean Concentration (GMC) for Anti-rubella Virus Immunoglobulin G (IgG)	8 weeks post vaccination	Used commercially available indirect enzyme-linked IgG immunoassays (EIAs; Wampole Laboratories, Princeton, New Jersey). An index standard ratio (ISR) of ≥1.10 on both runs of the respective assay was considered evidence of seropositivity for rubella virus. An ISR of at least 1.10 represents 10 IU/mL of rubella virus antibody, consistent with a protective level.All measles virus and rubella virus assays were performed at the National Measles and Rubella Reference Laboratories, Measles, Mumps, Rubella, and Herpesviruses Branch, Division of Viral Diseases, Centers for Disease Control and Prevention (Atlanta, Georgia).
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin A (IgA)	Visit 1 (pre-vaccination) and 8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin A (IgA)	Visit 1 (pre-vaccination) and 8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of \<20 U/mL are converted to 10 U/mL for calculation purposes.
Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin G (IgG)	Visit 1 (pre-vaccination) and 8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin G (IgG)	Visit 1 (pre-vaccination) and 8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. Rotavirus IgA and IgG values of \<20 U/mL are converted to 10 U/mL for calculation purposes.
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin A (IgA)	8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin G (IgG)	8 weeks post vaccination	Antirotavirus immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent assay at the Laboratory of Specialized Clinical Studies at the Cincinnati Children's Hospital Medical Center (Cincinnati, Ohio). A standard serum pool was used to determine arbitrary units of rotavirus IgA or IgG in each sample. A subject was considered seropositive if the IgA or IgG rotavirus antibody concentration was ≥20 U/mL.
Number/Percentage of Subjects Experiencing Immediate Post-vaccination Reactions Following Administration of Vaccine	30 minutes post-vaccination	Immediate reactogenicity was defined as local or systemic reactions occurring directly and up to 30 minutes after vaccine receipt, with an emphasis on allergic reactions.
Number/Percentage of Subjects Experiencing Solicited Adverse Events	14 days post-vaccination	Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. They included diarrhea, fever, vomiting, loss of appetite, irritability, and intussusception. Adverse events were graded for severity and relationship to vaccine.
Number/Percentage of Subjects Experiencing Unsolicited Non-serious Adverse Events	14 days post-vaccination	Solicited non-serious adverse events were collected based on recall at study visits 2 (Day 4) through 5 (Day 14) following administration of Rotarix® vaccine. Adverse events were graded for severity and relationship to vaccine.
Number/Percentage of Subjects Experiencing Serious Adverse Events	2 months after vaccination	An adverse event (AE) or suspected AE was considered "serious" if it resulted in any of the following outcomes: * Death * A life-threatening AE (the term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions Important medical events that may not result in death, be life threatening, or require hospitalization would have been considered severe adverse events when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition.