Safety of and Immune Response to a Meningitis Vaccine in HIV-Infected Children and Youth
- Conditions
- HIV InfectionsMeningitis
- Interventions
- Biological: Quadrivalent meningococcal conjugate vaccine
- Registration Number
- NCT00459316
- Brief Summary
Bacterial meningitis infection is common in youth 2 to 24 years of age in the United States. This disease can be treated by antibiotics, but mortality rates associated with meningitis of up to 53% have been estimated. Vaccination against meningitis may be effective in preventing this disease, especially for HIV-infected youth who have weakened immune systems. The purpose of this study was to determine the safety of and immune response to a preventive meningitis vaccine in HIV-infected youth.
- Detailed Description
In the United States, youth 2 to 24 years of age are at high risk for bacterial meningitis infection. Despite antibiotic treatment, the mortality rate for meningitis and sepsis can reach as high as 53% caused by Neisseria meningitidis. This rate could be higher in immunocompromised individuals, such as those infected with HIV. To prevent infection, vaccination against meningitis is recommended by the CDC at ages 11, 15, and 18. The quadrivalent meningococcal conjugate vaccine (MCV4) is a vaccine that has been observed to elicit an appropriate immune response to N. meningitidis and was approved by the FDA in January 2005. However, to date, no studies have been done to determine the safety and immunogenicity of this vaccine in HIV-infected individuals. The purpose of this study was to determine the safety and immunogenicity of MCV4 in HIV-infected youth 2 to 24 years of age.
The study was originally designed for participants to be followed for 72 weeks. Participants were enrolled in three groups by age and CD4% as follows:
Group 1: Age 11 to 24 years, CD4% of 15% or higher. Enrollment was further stratified by CD4%: 15% to \<25%, and \>= 25%.
Group 2: Age 11 to 24 years, CD4% \< 15%.
Group 3: Age 2 to 10 years, CD4% of 25% or higher.
At study entry, all study participants received one injection of MCV4 (Step 1). Participants were observed for 30 minutes post-injection to monitor for adverse events. A clinic visit was required 24 hours post-injection if the participant reported adverse events. At Week 24, participants in Group 1 who did not experience any disqualifying adverse events after the first injection were randomly assigned to receive a second injection of MCV4 or no further injections. Group 2, and Group 3 participants who had no disqualifying adverse events after the first injection received a second injection of MCV4 at Week 24 (Step 2).
There were five study visits in Steps 1 and 2; they occurred at study entry and at Weeks 4, 24, 28, and 72. At these visits, a physical exam, assessment of HIV-related symptoms, and blood collection occurred. In addition, study participants were contacted by telephone at Days 3 and 7 and Weeks 1, 6, and 25 after the first vaccination. Participants in Groups 1B and 2 who received a second injection were contacted by telephone at Weeks 30 and 48.
As of November 2010, due to data from this study (P1065) and recommendations from the Advisory Committee for Immunization Practices (ACIP) of the Center for Disease Control (CDC), eligible participants in Groups 1 (1A and 1B) and 3 of P1065 received a booster dose of MCV4 at approximately 3.5 years (+/- 6 months) after the initial MCV4 vaccination. Participants were then observed for 30 minutes post-injection to monitor for adverse events. Participants were also observed at Week 1 for vaccine adverse reactions.
This portion of the study (Step 3) lasted an additional 24 weeks. There were 4 study visits; they occurred at entry, at Days 7-8, and at Weeks 4 and 24. At these visits, a physical exam, assessment of HIV-related symptoms, and blood collection occurred. The purpose of this follow-up study was to determine the safety and immunogenicity of a MCV4 booster dose in HIV-infected participants who have previously received one or two MCV4 vaccinations on this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 384
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 Quadrivalent meningococcal conjugate vaccine Participants ≤11 to \<25 years of age with CD4% at screening ≥15%. All received Quadrivalent meningococcal conjugate vaccine at entry, those who were eligible were randomized at week 24, with Group 1B receiving a second Quadrivalent meningococcal conjugate vaccine at week 24. Those who were eligible received a booster dose of Quadrivalent meningococcal vaccine at 3.5 years. Group 2 Quadrivalent meningococcal conjugate vaccine Participants ≤11 to \<25 years of age with CD4% at screening \<15%; All receiving Quadrivalent meningococcal conjugate vaccine at entry, with those who were eligible receiving Quadrivalent meningococcal conjugate vaccine at week 24 and 3 years. Group 3 Quadrivalent meningococcal conjugate vaccine Participants \>=2 to \<11 years of age with CD4% at screening ≥ 25%; All received Quadrivalent meningococcal conjugate vaccine at entry, with those who were eligible receiving Quadrivalent meningococcal conjugate vaccine at week 24 and 3 years.
- Primary Outcome Measures
Name Time Method Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4. Study entry and Week 28 Serum bactericidal antibody titers were measured at study entry and Week 28 for each of the four serogroups in the MCV-4 vaccine. Response was defined as a 4-fold or greater increase from entry at Week 28.
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72 Week 72 Protective levels of antibody are titers ≥1:128.
Number of Participants With Immunogenicity at Step 3 Entry At 3.5 years (Step 3 entry) Immunogenicity was assessed for each serogroup by the number of participants with protective antibody levels (titers greater than or equal to 1:128)
Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline) At Study entry, Week 4 Serum bactericidal antibody titers were measured at study entry and Week 4 for each of the four serogroups in the MCV-4 vaccine. Response (seroconversion) was defined as a 4-fold or greater increase from entry at Week 4.
Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine. From administration of Dose 1 at week 0 to 42 days post-vaccination Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine. From administration of Dose 2 at week 24 to 6 weeks post-vaccination Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of Participants With 4-fold Memory Response in Step 3 Step 3 entry and Week 1 post-booster vaccine Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.
Number of Participants With Seropositive Memory Response (in Step 3) Step 3 entry and Week 1 post-booster vaccine Seropositive memory response was defined for each serogroup by having protective antibody levels (titer \>= 1:128) on Day 0 or change from seronegative to seropositive between booster dose (Day 0) and Day 7.
Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24 At Step 3 Weeks 4 and 24 post-booster vaccine Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)
Number of Participants With Primary Response (in Step 3) Step 3 entry and Week 4 post-booster vaccine Primary response was defined for each serogroup as a four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; OR a change from seronegative on day 0 to seropositive on day 28, but not between day 0 and day 7. Note: a primary response can only occur in the absence of any memory response.
- Secondary Outcome Measures
Name Time Method Immunogenic Response to Serogroup C in Group 2 At Weeks 4, 28, and 72 Immunogenic response as assessed by number of participants with protective antibody titers (\>= 1:128) to serogroup C in Group 2 (entry CD4%\<15)
Immunologic Memory or Primary Response for Serogroup C by Treatment Arm At Week 4 post-booster vaccination Immunologic Memory defined as:
1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or
2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7.
Primary Response defined as:
1. A four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; or
2. A change from titer \<1:128 on day 0 to titer ≥1:128on day 28, but not between day 0 and day 7.Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine. From administration of vaccination at Step 3 entry through 6 weeks post-vaccination Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry At 3.5 years Number of participants with protective antibody titers (rSBA\>=1:128) for serogroup C by treatment arm (1 vs. 2 doses) of Group 1 (entry CD4% \>= 15) at Step 3 entry
Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses) At Week 1 post-booster vaccination Evidence of immunologic memory according to each of the following definitions:
1. Secondary (anamnestic) response defined as a four-fold rise in Ab titers between day 0 (booster dose) and day 7; or
2. Seroprotection on day 0 or change from titer \<1:128 to titer ≥1:128 (seroprotection) between day 0 and day 7.
Trial Locations
- Locations (37)
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
🇺🇸Los Angeles, California, United States
Bronx-Lebanon CRS
🇺🇸Bronx, New York, United States
Rush Univ. Cook County Hosp. Chicago NICHD CRS
🇺🇸Chicago, Illinois, United States
WNE Maternal Pediatric Adolescent AIDS CRS
🇺🇸Worcester, Massachusetts, United States
Nyu Ny Nichd Crs
🇺🇸New York, New York, United States
Harbor UCLA Medical Ctr. NICHD CRS
🇺🇸Torrance, California, United States
Usc La Nichd Crs
🇺🇸Alhambra, California, United States
Tulane Univ. New Orleans NICHD CRS
🇺🇸New Orleans, Louisiana, United States
Univ. of Colorado Denver NICHD CRS
🇺🇸Aurora, Colorado, United States
Children's National Med. Ctr. Washington DC NICHD CRS
🇺🇸Washington, District of Columbia, United States
Howard Univ. Washington DC NICHD CRS
🇺🇸Washington, District of Columbia, United States
Children's Hospital of Los Angeles NICHD CRS
🇺🇸Los Angeles, California, United States
Univ. of Maryland Baltimore NICHD CRS
🇺🇸Baltimore, Maryland, United States
University of California, UC San Diego CRS
🇺🇸San Diego, California, United States
Pediatric Perinatal HIV Clinical Trials Unit CRS
🇺🇸Miami, Florida, United States
Miller Children's Hosp. Long Beach CA NICHD CRS
🇺🇸Long Beach, California, United States
South Florida CDTC Ft Lauderdale NICHD CRS
🇺🇸Fort Lauderdale, Florida, United States
USF - Tampa NICHD CRS
🇺🇸Tampa, Florida, United States
Children's Hospital of Michigan NICHD CRS
🇺🇸Detroit, Michigan, United States
Rutgers - New Jersey Medical School CRS
🇺🇸Newark, New Jersey, United States
Jacobi Med. Ctr. Bronx NICHD CRS
🇺🇸Bronx, New York, United States
Metropolitan Hosp. NICHD CRS
🇺🇸New York, New York, United States
Columbia IMPAACT CRS
🇺🇸New York, New York, United States
SUNY Stony Brook NICHD CRS
🇺🇸Stony Brook, New York, United States
DUMC Ped. CRS
🇺🇸Durham, North Carolina, United States
The Children's Hosp. of Philadelphia IMPAACT CRS
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital CRS
🇺🇸Houston, Texas, United States
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
🇵🇷San Juan, Puerto Rico
Seattle Children's Research Institute CRS
🇺🇸Seattle, Washington, United States
San Juan City Hosp. PR NICHD CRS
🇵🇷San Juan, Puerto Rico
Univ. of California San Francisco NICHD CRS
🇺🇸San Francisco, California, United States
Strong Memorial Hospital Rochester NY NICHD CRS
🇺🇸Rochester, New York, United States
Children's Hosp. of Boston NICHD CRS
🇺🇸Boston, Massachusetts, United States
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
🇺🇸Chicago, Illinois, United States
Univ. of Florida Jacksonville NICHD CRS
🇺🇸Jacksonville, Florida, United States
Boston Medical Center Ped. HIV Program NICHD CRS
🇺🇸Boston, Massachusetts, United States
St. Jude Children's Research Hospital CRS
🇺🇸Memphis, Tennessee, United States