Measles Antibody Seroconversion Clinical Trial
Official title:
Non-interference and Safety of Concomitant Administration of Measles-rubella and Rotavirus Vaccines at 9 Months of Age in Rural Bangladesh
| NCT number | NCT01700621 |
| Other study ID # | HS677 |
| Secondary ID | |
| Status | Completed |
| Phase | Phase 4 |
| First received | |
| Last updated | |
| Start date | January 2013 |
| Est. completion date | September 2013 |
| Verified date | February 2019 |
| Source | PATH |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 482 |
| Est. completion date | September 2013 |
| Est. primary completion date | September 2013 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 9 Months to 11 Months |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Bangladesh | ICDDR,B | Dhaka |
| Lead Sponsor | Collaborator |
|---|---|
| PATH |
Bangladesh,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Geometric Mean Concentration (GMC) for Measles Virus Serum Neutralization Antibodies | Sera were analyzed for the presence of measles virus serum neutralizing antibodies (SNAs), using a standardized plaque reduction neutralization (PRN) assay, in which PRN titers, defined as the serum dilutions that reduced the number of plaques by 50%, were calculated using the Kärber method [12]. A 1:100 dilution of World Health Organization (WHO) Second International Standard Anti-Measles Serum (IS, coded 66/202, supplied by the National Institute for Biological Standards and Control, South Mimms, United Kingdom) was tested in parallel with each serum specimen to calculate the reciprocal of the 50% end point titer determined by the PRN test. | 8 weeks post vaccination | |
| Other | Number of Participants With Rotavirus Vaccine Shedding | Based on 5 grams of stool sample. Vaccine shedding defined as presence of vaccine-type rotavirus in stool at 4 (+/-1) and/or 7 (+/-1) days post rotavirus vaccination detected by enzyme-linked immunosorbent assay (ELISA) and typed by reverse-transcriptase polymerase chain reaction (RT-PCR). | Day 0, Day 4 and Day 7 | |
| Primary | Percentage/Number of Subjects With Seroprotection for Measles Virus Serum Neutralization Antibodies | 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. |
8 weeks post vaccination | |
| Primary | Percentage/Number of Subjects With Seroprotection for Anti-measles Virus Immunoglobulin G (IgG) | 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). | 8 weeks post vaccination | |
| Secondary | Percentage/Number of Subjects With Seroconversion for Anti-rubella Virus Immunoglobulin G (IgG) | 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). | 8 weeks post vaccination | |
| Secondary | Geometric Mean Concentration (GMC) for Anti-rubella Virus Immunoglobulin G (IgG) | 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). | 8 weeks post vaccination | |
| Secondary | Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin A (IgA) | 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. | Visit 1 (pre-vaccination) and 8 weeks post vaccination | |
| Secondary | Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin A (IgA) | 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. | Visit 1 (pre-vaccination) and 8 weeks post vaccination | |
| Secondary | Percentage/Number of Subjects Seropositive for Anti-rotavirus Immunoglobulin G (IgG) | 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. | Visit 1 (pre-vaccination) and 8 weeks post vaccination | |
| Secondary | Geometric Mean Titer (GMT) of Anti-rotavirus Immunoglobulin G (IgG) | 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. | Visit 1 (pre-vaccination) and 8 weeks post vaccination | |
| Secondary | Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin A (IgA) | 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. | 8 weeks post vaccination | |
| Secondary | Percentage/Number of Subjects With Seroconversion for Anti-rotavirus Immunoglobulin G (IgG) | 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. | 8 weeks post vaccination | |
| Secondary | Number/Percentage of Subjects Experiencing Immediate Post-vaccination Reactions Following Administration of Vaccine | 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. | 30 minutes post-vaccination | |
| Secondary | Number/Percentage of Subjects Experiencing Solicited Adverse Events | 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. | 14 days post-vaccination | |
| Secondary | Number/Percentage of Subjects Experiencing Unsolicited Non-serious Adverse Events | 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. | 14 days post-vaccination | |
| Secondary | Number/Percentage of Subjects Experiencing Serious Adverse Events | 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. |
2 months after vaccination |