A Phase 4 interventional study of Measles-rubella (MR) vaccine at 6 months of age and Measles-rubella (MR) vaccine at 9 months of age in Measles, Rubella and Rubella Syndrome, Congenital, sponsored by Centers for Disease Control and Prevention. Completed at 1 site in Bangladesh. Open to participants aged 173 Days to 187 Days, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-16.
Sponsored by Centers for Disease Control and Prevention · Phase 4, Interventional, and Prevention
This is an open-label, randomized, 2-arm clinical trial in healthy infants in Bangladesh. The primary purpose of the study is to assess the immunogenicity of measles-rubella (MR) vaccine when delivered at 6 months. In addition, the study will establish the equality of MR vaccine seroconversion administered at 9 months following administration of an earlier MR vaccine dose at 6 months of age compared to MR vaccine dose administered at 9 months without previous MR vaccination. This study will also provide additional data on safety and tolerance of MR vaccine given at 6 months, and impact of maternal antibodies on immunogenicity of MR vaccine at 6 months.
Primary objectives:
Secondary objectives
In countries with low levels of circulating measles virus, and lower risk for measles infection, measles containing vaccine first dose (MCV1) is recommended at 12 months of age. In countries with high risk for measles, MCV1 is recommended at 9 months. In the past decade, many countries have been experiencing measles outbreaks with a high proportion of cases among infants \< 9 months of age, below the recommended age of routine MCV1.
Recent publications suggest that this may be due to the fact that the majority of infants now are born to mothers with vaccine induced immunity to measles, and who lose maternal antibodies much earlier, by age of 4-6 months. For example, in a measles outbreak in Malawi in 2010, 14% (17,858) of the estimated 134,000 cases occurred in children 0-8 months. In 2013, in a measles outbreak in Sri Lanka approximately 34% of measles cases were in children 6-12 months of age. Furthermore, in 2013 Jordan experienced a large measles outbreak with high proportion of young infants affected (6-9 months). WHO measles outbreak response guidelines recommend vaccinating children as young as 6 months during outbreaks. As an example, in response to a measles outbreak, Sri Lanka and Jordan conducted outbreak response immunization (ORI) that included infants 6 months of age despite the limited evidence on immunogenicity of MR vaccine at that age.
Some researchers suggest that routine MCV should be given before age of 9 months based on published data showing that infants born to mothers with vaccine induced measles immunity are born with lower concentration of maternal measles antibodies (MMA) and lose protection against measles infection at an earlier age. Measles vaccine immunogenicity depends on several factors, including presence of maternal measles antibodies (i.e., passively acquired measles antibodies may neutralize vaccine virus before a complete immune response develops resulting in primary vaccine failure.), maturity of immune system of the vaccine recipient, and strain of the measles vaccine used. So any decisions to alter the age of MCV1 dose should balance the potential risk of primary vaccine failure against the risk of measles infection and measles related complications, including death. Immunogenicity of measles vaccine given at 6 months is well studied; however, data on immunogenicity of combined MR vaccine administered at 6 months and its impact on MR vaccine effectiveness given at 9 months, is limited.
Because the number of infants born to mothers with vaccine induced immunity has been steadily increasing and most countries will be using MR vaccine routinely in the Expanded Program of Immunization (EPI), it is timely to conduct a study to assess immunogenicity of MR vaccine given at 6 months and its impact on a subsequent 9 month MR dose. The first dose of MCV given at 6 months is frequently referred to as MCV-0, indicating that two subsequent doses are needed to attain population seroprotection levels necessary to stop endemic transmission of the measles virus.
To improve the accuracy of interpretation of study results blood samples of mothers of enrolled infants will be tested for measles and rubella antibodies. This will also enable us to determine the proportion of mothers with undetectable, detectable and protective levels of antibodies, and to assess the relationship between the level of antibodies in mothers and their infants' maternal antibodies.
This study will be conducted in a single site in rural Bangladesh at Matlab. Matlab is a major rural field site for icddr,b, where for the past 50 years continuous health and demographic information was collected on >200,000 population.
From 2007 to 2010, icddr,b, the Ministry of Health (MOH) in collaboration with other international organizations conducted several randomized vaccine effectiveness studies.
This study will be an open-label, randomized, 2-arm clinical trial. 620 children will be enrolled and randomized at 6 months of age to one of two study arms. The primary objectives of this study are to assess the immunogenicity of MR vaccine at 6 months, and assess equality of MR vaccine seroconversion administered at 9 months following administration of an earlier MR vaccine dose at 6 months of age compared with MR vaccine dose administered at 9 months only without previous MR vaccination. The study will enroll generally healthy 6 month old infants living in Matlab and who have never received an MR vaccine dose and have no history of measles or rubella. Participants will be followed to 11 months of age.
Infants in this study will be randomly assigned to one of two arms. Infants in Study Arm A will receive MR vaccine at 6 months of age (at enrolment) and at 9 months. Infants in Study arm B will receive MR vaccine only at 9 months.
Blood specimens will be collected from all infants at 6, 9 and 11 months of age. The 6 month sample is a pre-vaccination sample and mainly will be used to determine maternal antibody levels. For arm A, the sample collected at 9 months before the second MR dose will be used to assess antibody levels after the first MR dose at 6 months of age. For study Arm B, the 9 month sample will be used to assess measles and rubella antibody decay rate. The sample collected at 11 months will be used to assess immune response to either a two dose or a one dose schedule (arms A and B, respectively).
134 studies on the registry are indexed under Measles; 17 are open to participants now.
This study's enrollment of 637 is below the median of 852 across 105 interventional studies indexed under Measles.
Browse Measles studies →Centers for Disease Control and Prevention is the lead sponsor of 275 studies on the registry; 2 are open to participants now.
Of its 11 completed or terminated interventional studies of FDA-regulated products, 8 (73%) have results posted.
Counted across the registry records on this site, refreshed daily.
Age is based on the age of the infant.
Inclusion Criteria: INFANTS:
Inclusion criteria: MOTHERS:
Exclusion Criteria: INFANTS:
Exclusion criteria: MOTHERS:
Temporary exclusion: INFANTS:
Infants receive a measles-rubella vaccine at 6 and 9 months. Infants receive a standard dose according to the vaccine package insert each time. (Mothers receive no intervention.)
Biological: Measles-rubella (MR) vaccine at 6 months of age · Biological: Measles-rubella (MR) vaccine at 9 months of age
Infants receive a measles-rubella vaccine at 9 months only. Infants receive a standard dose according to the vaccine package insert. (Mothers receive no intervention.)
Biological: Measles-rubella (MR) vaccine at 9 months of age
Infants receive a standard dose according to the vaccine package insert. (Mothers receive no intervention.)
Also known as: Early dose
Infants receive a standard dose according to the vaccine package insert. (Mothers receive no intervention.)
Also known as: Standard dose
Percent of Infants Who Were Seropositive After Immunization at 6 Months (Assessed at 9-month Visit)
\# seropositive infants at 9 months/ # of infants in the arm Measles neutralizing antibody titers as measured by plaque reduction neutralization assay is defined as seropositive at ≥ 120 mIU/mL. Rubella antibody titers as measured by ELISA are considered seropositive at \>10 IU/mL. Abbreviations mIU =milli-International unit; IU International units; mL milliliter
Time frame: Infant antibody titer at 9 months.
Percent of Infants Who Were Seropositive After Immunization at 9 Months (Assessed at 11-month Visit)
\# seropositive at 11 months of age/ # of infants in the arm \* 100 Measles neutralizing antibody titers as measured by plaque reduction neutralization assay is defined as seropositive at ≥ 120 mIU/mL. Rubella antibody titers as measured by ELISA are considered seropositive at \>10 IU/mL. Abbreviations mIU =milli-International unit; IU International units; mL milliliter
Time frame: Infant antibody titer at 11 months.
Adverse Effects Following Immunization (AEFI) at the Age of 6 Months
To assess the frequency of adverse reactions following administration of MR vaccine at the age of 6 months. There were multiple assessment timeframes relative to the first immunization. 30 minutes direct observation at the clinic site and 48-hour follow-up visit by study staff at the home.
Time frame: 0-30 minutes; 48-hour visit.
Immunogenicity at 9 Months - Measles
The average antibody levels of infants who seroconverted or responded to the measles component of the vaccine. This measures the number of antibodies against the measles virus per volume of blood. A larger number means more antibodies are present and suggests a better ability to detect and prevent infection by the measles virus.
Time frame: At 9 months and 11 months of age
Immunogenicity at 9 Months - Rubella
The average antibody levels of infants who seroconverted or responded to the rubella component of the vaccine. This measures the number of antibodies against the rubella virus per volume of blood. A larger number means more antibodies are present and suggests a better ability to detect and prevent infection by the rubella virus.
Time frame: At 9 months and 11 months of age
Measles and Rubella Titers of Enrolled Mothers
To assess the distribution of mothers with undetectable, detectable and protective levels of measles and rubella immunoglobulin G (IgG) antibodies
Time frame: Baseline enrollment (when infant was 6 months of age)
Pearson Correlation Coefficient of Infant Measles and Rubella Antibody Levels at 6, 9, and 11 Months of Age Compared to Maternal Antibody Levels at Baseline (a Proxy for Infant Antibody Levels at Birth).
Pearson correlation coefficient, by arm at each study timepoint. It quantifies the linear relationship between two sets of variables; we compare the infant antibody levels (y axis) to that of the mother at baseline (x-axis), a proxy for infant antibody levels at birth. This is usually presented as a scatter plot. A coefficient approaching 1 or -1 indicates a strong correlation, while a coefficient near zero indicates no correlation.
Time frame: baseline (6 months infant age); 2nd blood draw (9 months of age) and 3rd blood draw (at 11 months of age)
Half-life and Decay of Maternal Measles and Rubella Antibodies.
To estimate the half-life of decay of maternal measles and rubella antibodies in infants
Time frame: Day 1 to day 84
| Milestone | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| Started | 312 | 308 |
| Completed | 303 | 294 |
| Not completed | 9 | 14 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Lost to follow-up | 5 | 11 |
| Withdrew: Withdrawal by subject | 4 | 2 |
\# seropositive infants at 9 months/ # of infants in the arm Measles neutralizing antibody titers as measured by plaque reduction neutralization assay is defined as seropositive at ≥ 120 mIU/mL. Rubella antibody titers as measured by ELISA are considered seropositive at \>10 IU/mL. Abbreviations mIU =milli-International unit; IU International units; mL milliliter
| percentage of infants | Group A: |
|---|---|
| Measles | 94 (90 to 96) |
| Rubella | 94 (91 to 96) |
\# seropositive at 11 months of age/ # of infants in the arm \* 100 Measles neutralizing antibody titers as measured by plaque reduction neutralization assay is defined as seropositive at ≥ 120 mIU/mL. Rubella antibody titers as measured by ELISA are considered seropositive at \>10 IU/mL. Abbreviations mIU =milli-International unit; IU International units; mL milliliter
| percentage of infants | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| Measles | 99 (97 to 100) | 100 (98 to 100) |
| Rubella | 99 (96 to 100) | 100 (98 to 100) |
To assess the frequency of adverse reactions following administration of MR vaccine at the age of 6 months. There were multiple assessment timeframes relative to the first immunization. 30 minutes direct observation at the clinic site and 48-hour follow-up visit by study staff at the home.
| Participants | Group A: Early Dose |
|---|---|
| Redness at the injection site (in 30 minutes) | 3 |
| Redness at the injection site (0.5 to 48 hours) | 0 |
| Fever (in 48 hours) | 7 |
| Cough, coryza, sneezing, or cold (in 48 hours) | 5 |
| Rash (in 48 hours) | 1 |
| No Vaccine Reaction reported (in 48 hours) | 285 |
The average antibody levels of infants who seroconverted or responded to the measles component of the vaccine. This measures the number of antibodies against the measles virus per volume of blood. A larger number means more antibodies are present and suggests a better ability to detect and prevent infection by the measles virus.
| mIU/mL | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| IgG at 9 months of age | 914 (584 to 1353) | — |
| IgG at 11 months of age | 1453 (1057 to 2094) | 1311 (881 to 1976) |
The average antibody levels of infants who seroconverted or responded to the rubella component of the vaccine. This measures the number of antibodies against the rubella virus per volume of blood. A larger number means more antibodies are present and suggests a better ability to detect and prevent infection by the rubella virus.
| IU/mL | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| IgG at 9 months of age | 102 (59 to 166) | — |
| IgG at 11 months of age | 94 (60 to 137) | 155 (91 to 228) |
To assess the distribution of mothers with undetectable, detectable and protective levels of measles and rubella immunoglobulin G (IgG) antibodies
| Participants | Group A: Mothers | Group B: Mothers |
|---|---|---|
| Measles IgG (Undetectable: <4mIU/mL; Protective: at least 153 mIU/mL) — Undetectable | 0 | 0 |
| Measles IgG (Undetectable: <4mIU/mL; Protective: at least 153 mIU/mL) — Detectable | 46 | 37 |
| Measles IgG (Undetectable: <4mIU/mL; Protective: at least 153 mIU/mL) — Protective | 255 | 255 |
| Rubella IgG (Undetectable: <0.08 IU/mL; Protective: at least 9·36 IU/mL) — Undetectable | 0 | 0 |
| Rubella IgG (Undetectable: <0.08 IU/mL; Protective: at least 9·36 IU/mL) — Detectable | 52 | 53 |
| Rubella IgG (Undetectable: <0.08 IU/mL; Protective: at least 9·36 IU/mL) — Protective | 249 | 239 |
Pearson correlation coefficient, by arm at each study timepoint. It quantifies the linear relationship between two sets of variables; we compare the infant antibody levels (y axis) to that of the mother at baseline (x-axis), a proxy for infant antibody levels at birth. This is usually presented as a scatter plot. A coefficient approaching 1 or -1 indicates a strong correlation, while a coefficient near zero indicates no correlation.
| Pearson correlation coefficient (r) | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| Measles baseline (6 months) | 0.72 | 0.66 |
| Measles (9 months) | -0.26 | 0.32 |
| Measles (11 months) | -0.03 | 0.02 |
| Rubella baseline (6 months) | 0.74 | 0.74 |
| Rubella (9 months) | -0.27 | 0.51 |
| Rubella (11 months) | -0.19 | -0.11 |
To estimate the half-life of decay of maternal measles and rubella antibodies in infants
Results for this outcome have not been posted.
Collected over Infants were assessed 0-30 minutes following immunization at the clinic, and parents were queried for adverse events at each subsequent study visit, up to 5 months in total duration. Arm A also received a safety monitoring visit at home 48 hours after immunization following the 6-month visit.. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A: Early Dose | 0/312 (0%) | 10/312 (3.2%) | 38/312 (12.2%) |
| Group B: Standard Dose | 1/308 (0.3%) | 7/308 (2.3%) | 31/308 (10.1%) |
| Event | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| Hospitalization: otherInfections and infestations | 6/312 | 2/308 |
| Hospitalization: Respiratory InfectionsInfections and infestations | 5/312 | 4/308 |
| Surgical procedureSurgical and medical procedures | 1/312 | 1/308 |
| AnaphylaxisImmune system disorders | 0/312 | 0/308 |
| Event | Group A: Early Dose | Group B: Standard Dose |
|---|---|---|
| Respiratory InfectionInfections and infestations | 29/312 | 25/308 |
| DiarrheaInfections and infestations | 7/312 | 5/308 |
| Varicella (Chicken Pox)Infections and infestations | 6/312 | 2/308 |
Group A and group B, each had 2 participants without laboratory results and were removed from the analysis.
| Age, Continuous(days) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Mean | 179.8 ± 3.3 | 179.5 ± 3.3 | 179.7 ± 3.3 |
| Age, Continuous(years) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Mean | 26.5 ± 5.4 | 26.4 ± 5.6 | 26.5 ± 5.5 |
| Sex: Female, Male(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Female | 156 | 146 | 302 |
| Male | 145 | 146 | 291 |
| Race and Ethnicity Not Collected(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Stunting present(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Count of participants | 29 | 35 | 64 |
| Wasting present(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Count of participants | 15 | 12 | 27 |
| Measles seropositivity (Infants)(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Count of participants | 10 | 6 | 16 |
| Rubella seropositivity (Infants)(Participants) | Group A: Early Dose | Group B: Standard Dose | Total |
|---|---|---|---|
| Count of participants | 8 | 9 | 17 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2017 to primary completion in Mar 2018, 12 months.
Results were first posted in Jul 2025, 7 years 3 months after primary completion.
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