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CompletedNCT00459316Updated Nov 3, 2021Results posted

Safety of and Immune Response to a Meningitis Vaccine in HIV-Infected Children and Youth

A Phase 1/2 interventional study of Quadrivalent meningococcal conjugate vaccine in HIV Infections and Meningitis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 37 sites in 2 countries. Open to participants aged 2 Years to 24 Years. Per ClinicalTrials.gov, last updated 2021-11-03.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Prevention

Phase
Phase 1/2
Study type
Interventional
Enrollment
384
Allocation
Randomized
Ages
2 Years to 24 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • HIV Infections
  • Meningitis

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03

In context

Meningitis

373 studies on the registry are indexed under Meningitis; 32 are open to participants now.

This study's enrollment of 384 is above the median of 211 across 257 interventional studies indexed under Meningitis.

Browse Meningitis studies →

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.

Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years to 24 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria for Steps 1, 2, and 3:

  • HIV-infected
  • Age greater than or equal to 2 and less than 25 years (Steps 1 and 2 only)
  • CD4% documented within 120 days of study entry
  • Participants on antiretroviral therapy (ART) must have been on stable ART regimen for at least 90 days prior to study entry
  • Able and willing to complete all study immunizations and evaluations
  • Parent or guardian willing to provide informed consent, if applicable
  • Participants and/or their partners who are sexually active had to agree to use at least one of the following methods of contraception as long as they are on the study: hormonal birth control drugs (oral, injectable or transdermal); male or female condoms with or without a spermicide; diaphragm/cervical cap with spermicide; intrauterine device (IUD)

Inclusion Criteria specific to Step 3:

  • Participants must have been enrolled in Groups 1 or 3 of previous versions of P1065
  • Participants did not have to be less than 25 years of age
  • Participants must have had serology data from Weeks 0, 4, and 28 from their previous participation in P1065
  • Participants must have been within 3.5 years +/- 6 months from the first MCV4 dose received in a previous version of P1065

Exclusion Criteria for Step 1:

  • Any nonstudy vaccine on study entry day
  • Any inactive vaccine within 2 weeks prior to study entry
  • Plans to receive any vaccine 2 weeks after the first injection
  • Receipt of any live nonstudy vaccine within 4 weeks prior to study entry
  • Meningococcal conjugate vaccine at any time prior to study entry
  • Meningococcal polysaccharide vaccine within 2 years prior to study entry
  • Known hypersensitivity to any component of the MCV4 vaccine, including diphtheria toxoid
  • Known hypersensitivity to dry natural rubber latex
  • Life-threatening reaction after previous administration of a vaccine containing similar components
  • Family history or personal history of Guillain-Barre Syndrome (GBS)
  • Clinically significant diseases that, in the investigator's opinion, would interfere with the study
  • Current immunomodulatory therapy, including IL-2, any interferon product, GM-CSF, or thalidomide. Participants taking G-CSF or erythropoietin were not excluded.
  • Current immunosuppressive therapy, including equivalent of 1 mg/kg/per day or more of prednisone 2 weeks prior to study entry OR planned corticosteroid therapy lasting 2 weeks or longer. Participants using nonsteroidal anti-inflammatory agents and inhaled corticosteroids are not excluded.
  • Cancer within 12 weeks of study entry
  • Cancer treatment currently or within 12 weeks of study entry
  • Loss of strength in lower extremity within 24 weeks prior to study entry
  • Bleeding disorder or anticoagulant therapy prior to study entry
  • Absence of ankle and patellar deep tendon reflexes (DTRs) (all four)
  • Recent receipt of IGIV or any blood or immunoglobulin product (except washed blood cells). More information about this criterion can be found in the protocol.
  • Other acute or chronic medical or surgical conditions or contraindications that, in the opinion of the investigator, might have interfered with the study
  • Any new and unresolved Grade 3 or higher laboratory toxicity within 120 days prior to study entry
  • Any new and unresolved Grade 3 or higher clinical toxicity within 120 days prior to study entry
  • Pregnancy or breastfeeding

Exclusion Criteria for Step 2:

  • New occurrence or awareness of GBS in the participant or participant's family since study entry
  • Loss of strength in lower extremity or extremities since first vaccination
  • Absence of ankle and patellar DTRs (all four)
  • New diagnosis of active cancer, or chemotherapy treatment of an established cancer diagnosis since study entry
  • Any Grade 4 toxicity since last vaccination. Participants who experience toxicities unrelated to the vaccine are not excluded.
  • Change in ART in the 90 days prior to second vaccination
  • Certain Grade 3 toxicities. More information on this criterion can be found in the protocol.
  • Treatment with immunosuppressive or immunomodulation therapy (other than corticosteroids) within 60 days of planned second vaccination
  • Severe allergic reaction requiring medical intervention within 24 hours of the first vaccination
  • New diagnosis of any coagulation disorder that would contraindicate intramuscular injection
  • Toxicity from first vaccination. More information on this criterion can be found in the protocol.
  • Any new diseases that the investigator judges to be clinically significant OR clinically significant findings since the first vaccination that, in the opinion of the investigator, would interfere with the study
  • Any new clinical Grade 3 or higher toxicity that has not resolved within 2 weeks prior to planned second vaccination
  • Pregnancy or breastfeeding. Pregnant or breastfeeding participants were to be followed to pregnancy outcome.

Exclusion Criteria for Step 3:

  • Receipt of any dose of non-study meningococcal vaccine since initial enrollment into P1065
  • New occurrence or new awareness of GBS in the participant or participant's family since the last P1065 study visit
  • Loss of strength in lower extremity or extremities since the last MCV4 vaccination
  • Absence of ankle and patellar Deep Tendon Reflexes (DTRs) (all 4)
  • New diagnosis of an active malignancy, or chemotherapy treatment of an established diagnosis since the last P1065 study visit
  • New diagnosis or suspected disease of the immune system since the last P1065 study visit
  • Participant or legal guardian refuses further vaccine
  • Participant requiring treatment with medications that were disallowed while on this study (see protocol)
  • Grade 3 or higher toxicities (for example, Grade 3 seizure or allergic reaction) secondary to receipt of vaccine in previous version of P1065 meriting vaccine discontinuation, as determined by the IMPAACT P1065 Protocol Team and the site principal investigator
  • Current immunomodulatory therapy, including IL-2, any interferon product, GM-CSF, or thalidomide [Note: G-CSF and erythropoietin are allowed]
  • Current immunosuppressive therapy, including the equivalent of greater than or equal to 1 mg/kg/per day of prednisone in the 2 weeks preceding study entry
  • Participants for whom long-term corticosteroid therapy (greater than or equal to 2 weeks) was anticipated were excluded [Note: non-steroidal anti-inflammatory agents and inhaled, intranasal and topical corticosteroids were allowed]
  • A severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention, occurring within 24 hours of the first vaccine and potentially attributable to that first vaccine
  • New diagnosis of any coagulation disorder that would contraindicate IM injections since the last P1065 study visit
  • Breastfeeding
  • Any new diseases which the investigators judged to be clinically significant (other than HIV infection) or clinically significant findings since enrollment into P1065 that, in the investigators' opinion, would have compromise the outcome of this study
  • Any new greater than or equal to grade 3 clinical toxicity that is not related to vaccine and had not resolved within 2 weeks before entry into Step 3
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
384 participants (actual)

Study arms

  • Experimental
    Group 1

    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.

    Biological: Quadrivalent meningococcal conjugate vaccine

  • Experimental
    Group 2

    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.

    Biological: Quadrivalent meningococcal conjugate vaccine

  • Experimental
    Group 3

    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.

    Biological: Quadrivalent meningococcal conjugate vaccine

Interventions

  • BiologicalQuadrivalent meningococcal conjugate vaccine

    MCV4 vaccine (4 µg each of meningococcal A, C, Y, and W-135 polysaccharides conjugated to approximately 48 µg of diphtheria toxoid protein carrier ) was given by injection intramuscularly at least once and no more than three times for each participant, depending on adverse reactions.

    Also known as: MCV4

06

What researchers measure

Primary outcomes

  1. 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.

    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.

    Time frame: Study entry and Week 28

  2. 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)

    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.

    Time frame: At Study entry, Week 4

  3. Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72

    Protective levels of antibody are titers ≥1:128.

    Time frame: Week 72

  4. Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.

    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.

    Time frame: From administration of Dose 1 at week 0 to 42 days post-vaccination

  5. Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.

    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.

    Time frame: From administration of Dose 2 at week 24 to 6 weeks post-vaccination

  6. Number of Participants With Immunogenicity at 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)

    Time frame: At 3.5 years (Step 3 entry)

  7. Number of Participants With 4-fold Memory Response in Step 3

    Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.

    Time frame: Step 3 entry and Week 1 post-booster vaccine

  8. Number of Participants With Seropositive Memory Response (in Step 3)

    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.

    Time frame: Step 3 entry and Week 1 post-booster vaccine

  9. Number of Participants With Primary Response (in Step 3)

    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.

    Time frame: Step 3 entry and Week 4 post-booster vaccine

  10. Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24

    Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)

    Time frame: At Step 3 Weeks 4 and 24 post-booster vaccine

Secondary outcomes

  1. Immunogenic Response to Serogroup C in Group 2

    Immunogenic response as assessed by number of participants with protective antibody titers (\>= 1:128) to serogroup C in Group 2 (entry CD4%\<15)

    Time frame: At Weeks 4, 28, and 72

  2. Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry

    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

    Time frame: At 3.5 years

  3. Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)

    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.

    Time frame: At Week 1 post-booster vaccination

  4. Immunologic Memory or Primary Response for Serogroup C by Treatment Arm

    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.

    Time frame: At Week 4 post-booster vaccination

  5. 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.

    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.

    Time frame: From administration of vaccination at Step 3 entry through 6 weeks post-vaccination

07

Results

Posted May 12, 2014

Participant flow

Steps 1 & 2
Participant flow — Steps 1 & 2
MilestoneGroup 1: CD4%≥15, Age ≤11 to <25Group 2: CD4%<15, Age ≤11 to <25Group 3: Age ≥2 to <11, CD4%≥25
Started2803959
Completed2593257
Not completed2172
Withdrew: Other eligibility failure110
Withdrew: Death110
Withdrew: Not able to get to clinic740
Withdrew: Withdrawal by subject610
Withdrew: Not willing to adhere to regulations100
Withdrew: Lost to follow-up502
Step 3
Participant flow — Step 3
MilestoneGroup 1: CD4%≥15, Age ≤11 to <25Group 2: CD4%<15, Age ≤11 to <25Group 3: Age ≥2 to <11, CD4%≥25
Started152040
Completed149039
Not completed301
Withdrew: Withdrawal by subject301

Outcome measures

PrimaryNumber 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.

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.

Time frame:
Study entry and Week 28
Reported as:
Number · participants
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.
participantsGroup 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3
Week 28 reponders, serogroup A27 (0.87 to 0.99)60 (0.40 to 0.69)8 (0.19 to 0.64)43 (0.75 to 0.95)
Week 28 reponders, serogroup C28 (0.44 to 0.74)49 (0.63 to 0.85)1 (0.001 to 0.27)39 (0.66 to 0.90)
Week 28 reponders, serogroup W-13536 (0.50 to 0.78)61 (0.70 to 0.90)0 (0 to 0.18)49 (0.93 to 1.00)
Week 28 reponders, serogroup Y32 (0.62 to 0.88)54 (0.83 to 0.97)1 (0.001 to 0.25)41 (0.70 to 0.93)
PrimaryNumber 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)

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.

Time frame:
At Study entry, Week 4
Reported as:
Number · participants
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)
participantsGroup 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3
Week 4 Seroconverters, serogroup A61107545
Week 4 Seroconverters, serogroup C4489321
Week 4 Seroconverters, serogroup W-13566118648
Week 4 Seroconverters, serogroup Y49100837
PrimaryLong-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72

Protective levels of antibody are titers ≥1:128.

Time frame:
Week 72
Reported as:
Number · participants
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72
participantsGroup 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3
Week 72 Responders, serogroup A3982435
Week 72 Responders, serogroup C1736120
Week 72 Responders, serogroup W-1353683642
Week 72 Responders, serogroup Y4980540
PrimaryNumber of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.

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.

Time frame:
From administration of Dose 1 at week 0 to 42 days post-vaccination
Reported as:
Number · participants
Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.
participantsGroup 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3
Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.3130
Statistical analysis
  • Group 1 (15<CD4%<25) vs Group 1 (CD4%≥25) vs Group 2 · Fisher Exact · p = 0.03 (Two-sided p-value \<0.05 was specified as statistically significant a priori. There were no adjustments for multiple outcomes.)
PrimaryNumber of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.

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.

Time frame:
From administration of Dose 2 at week 24 to 6 weeks post-vaccination
Reported as:
Number · participants
Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.
participantsGroup 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3
Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.0020
Statistical analysis
  • Group 1 (15<CD4%<25) vs Group 1 (CD4%≥25) vs Group 2 · Fisher Exact · p = 0.01 (Two sided-p-value \<0.05 was specified as statistically significant a priori. No adjustment for multiple primary outcomes was made.)
PrimaryNumber of Participants With Immunogenicity at 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)

Time frame:
At 3.5 years (Step 3 entry)
Reported as:
Number · participants
Number of Participants With Immunogenicity at Step 3 Entry
participantsGroup 1AGroup 1BGroup 3
Immunogenicity, Serogroup A47 (.52 to .75)48 (.51 to .73)34 (.73 to .96)
Immunogenicity, Serogroup C19 (.16 to .38)20 (.17 to .37)9 (.11 to .39)
Immunogenicity, Serogroup W-13530 (.30 to .53)35 (.34 to .57)23 (.42 to .74)
Immunogenicity, Serogroup Y39 (.41 to .65)33 (.32 to .55)24 (.45 to .77)
PrimaryNumber of Participants With 4-fold Memory Response in Step 3

Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.

Time frame:
Step 3 entry and Week 1 post-booster vaccine
Reported as:
Number · participants
Number of Participants With 4-fold Memory Response in Step 3
participantsGroup 1AGroup 1BGroup 3
4-fold memory responders, serogroup A54 (0.62 to 0.84)49 (0.61 to 0.83)33 (0.78 to 1.00)
4-fold memory responders, serogroup C56 (0.65 to 0.86)50 (0.63 to 0.84)34 (0.81 to 0.99)
4-fold memory responders, serogroup W-13563 (0.76 to 0.93)55 (0.73 to 0.92)33 (0.78 to 0.98)
4-fold memory responders, serogroup Y54 (0.62 to 0.84)51 (0.67 to 0.88)33 (0.78 to 0.98)
PrimaryNumber of Participants With Seropositive Memory Response (in Step 3)

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.

Time frame:
Step 3 entry and Week 1 post-booster vaccine
Reported as:
Number · participants
Number of Participants With Seropositive Memory Response (in Step 3)
participantsGroup 1AGroup 1BGroup 3
Seropositive memory responder, serogroup A65 (0.80 to 0.95)61 (0.83 to 0.98)35 (0.85 to 1.00)
Seropositive memory responder, serogroup C62 (0.75 to 0.92)55 (0.71 to 0.90)34 (0.81 to 0.99)
Seropositive memory responder, serogroup W-13565 (0.80 to 0.95)60 (0.80 to 0.96)34 (0.81 to 0.99)
Seropositive memory responder, serogroup Y67 (0.83 to 0.97)57 (0.74 to 0.93)33 (0.78 to 0.98)
PrimaryNumber of Participants With Primary Response (in Step 3)

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.

Time frame:
Step 3 entry and Week 4 post-booster vaccine
Reported as:
Number · participants
Number of Participants With Primary Response (in Step 3)
participantsGroup 1AGroup 1BGroup 3
Primary responder, serogroup A2 (0 to 0.10)2 (0 to 0.10)0 (0 to 0.10)
Primary responder, serogroup C1 (0 to 0.07)1 (0 to 0.08)1 (0 to 0.15)
Primary responder, serogroup W-1351 (0 to 0.07)0 (0 to 0.05)2 (0.01 to 0.19)
Primary responder, serogroup Y1 (0 to 0.07)2 (0 to 0.11)2 (0.01 to 0.19)
SecondaryImmunogenic Response to Serogroup C in Group 2

Immunogenic response as assessed by number of participants with protective antibody titers (\>= 1:128) to serogroup C in Group 2 (entry CD4%\<15)

Time frame:
At Weeks 4, 28, and 72
Reported as:
Number · participants
Immunogenic Response to Serogroup C in Group 2
participantsWeek 4Week 28Week 72
Immunogenic Response to Serogroup C in Group 2441
SecondaryNumber of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry

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

Time frame:
At 3.5 years
Reported as:
Number · participants
Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry
participantsGroup 1AGroup 1BGroup 3: Age 2-<6Group 3: Age 6-<11
Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry191736
SecondaryImmunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)

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.

Time frame:
At Week 1 post-booster vaccination
Reported as:
Number · participants
Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)
participantsGroup 1AGroup 1B
Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)6561
SecondaryImmunologic Memory or Primary Response for Serogroup C by Treatment Arm

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.

Time frame:
At Week 4 post-booster vaccination
Reported as:
Number · participants
Immunologic Memory or Primary Response for Serogroup C by Treatment Arm
participantsGroup 1AGroup 1B
Immunologic Memory or Primary Response for Serogroup C by Treatment Arm6457
SecondarySafety, 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.

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.

Time frame:
From administration of vaccination at Step 3 entry through 6 weeks post-vaccination
Reported as:
Number · participants
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.
participantsGroup 1Group 3
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.20
PrimaryNumber of Participants With Immunogenicity at Step 3 Weeks 4 and 24

Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)

Time frame:
At Step 3 Weeks 4 and 24 post-booster vaccine
Reported as:
Number · participants
Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24
participantsGroup 1AGroup 1BGroup 3
Week 4 immunogenicity, serogroup A66 (0.81 to 0.96)67 (0.86 to 0.98)37 (0.86 to 1.00)
Week 4 immunogenicity, serogroup C61 (0.73 to 0.91)60 (0.77 to 0.94)35 (0.78 to 0.98)
Week 4 immunogenicity, serogroup W-13567 (0.83 to 0.97)64 (0.82 to 0.97)37 (0.86 to 1.00)
Week 4 immunogenicity, serogroup Y67 (0.83 to 0.97)62 (0.78 to 0.95)35 (0.78 to 0.98)
Week 24 immunogenicity, serogroup A58 (0.70 to 0.89)59 (0.73 to 0.92)30 (0.75 to 0.98)
Week 24 immunogenicity, serogroup C41 (0.44 to 0.68)46 (0.52 to 0.76)24 (0.53 to 0.86)
Week 24 immunogenicity, serogroup W-13557 (0.67 to 0.87)53 (0.63 to 0.85)32 (0.84 to 1.00)
Week 24 immunogenicity, serogroup Y58 (0.68 to 0.88)52 (0.61 to 0.84)31 (0.79 to 0.99)

Adverse events

Collected over From study entry through Step 3, week 24 (4 years ). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Group 1 (15<CD4%≤25)—4/127 (3.1%)94/127 (74%)
Group 1 (CD4%≥25)—5/153 (3.3%)113/153 (73.9%)
Group 2—5/39 (12.8%)33/39 (84.6%)
Group 3—2/59 (3.4%)47/59 (79.7%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventGroup 1 (15<CD4%≤25)Group 1 (CD4%≥25)Group 2Group 3
Candida sepsisInfections and infestations0/1270/1531/390/59
MigraineNervous system disorders0/1270/1531/390/59
Foetal deathPregnancy, puerperium and perinatal conditions0/1270/1531/390/59
NephrolithiasisRenal and urinary disorders0/1270/1531/390/59
RashSkin and subcutaneous tissue disorders0/1270/1531/390/59
PneumoniaInfections and infestations0/1270/1530/391/59
Muscular weaknessMusculoskeletal and connective tissue disorders0/1270/1530/391/59
Abortion spontaneousPregnancy, puerperium and perinatal conditions1/1272/1530/390/59
HepatitisHepatobiliary disorders1/1270/1530/390/59
Pelvic inflammatory diseaseInfections and infestations1/1270/1530/390/59
Most frequent other events
Showing 10 of 63
Most frequent other events
EventGroup 1 (15<CD4%≤25)Group 1 (CD4%≥25)Group 2Group 3
Neutrophil count decreasedInvestigations31/12736/15312/3919/59
PyrexiaGeneral disorders13/12711/1536/3912/59
CoughRespiratory, thoracic and mediastinal disorders20/12723/1533/3912/59
Abdominal painGastrointestinal disorders11/12714/1537/393/59
Oral candidiasisInfections and infestations3/1271/1537/390/59
Oropharyngeal painRespiratory, thoracic and mediastinal disorders12/12713/1537/397/59
Haemoglobin decreasedInvestigations6/1274/1536/390/59
White blood cell count decreasedInvestigations8/1274/1536/390/59
Attention deficit/hyperactivity disorderPsychiatric disorders3/1270/1530/399/59
Adverse eventGeneral disorders14/12712/1530/398/59

Baseline characteristics

All participants who started study treatment.

Age, Continuous
Age, Continuous(years)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
Median18 (11 to 24)16 (11 to 24)20 (14 to 24)6 (2 to 10)16 (2 to 24)
Sex: Female, Male
Sex: Female, Male(Participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
Female44701631161
Male83832328217
Race
Race(participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
Asian11024
Native Hawaiian or other Pacific islander10012
Black or African American72692234197
White47751421157
American Indian23005
More than One race03205
Unknown42118
Ethnicity
Ethnicity(participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
Hispanic or Latino44611618139
Not Hispanic or Latino83892340235
Unknown03014
Screening CD4%
Screening CD4%(percent)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
Median20.0 (14.0 to 24.9)33.0 (25.0 to 53.1)8.5 (1.0 to 14.0)36.0 (25.0 to 56.0)27.9 (1.0 to 56.0)
Entry plasma HIV RNA viral load, copies/mL
Entry plasma HIV RNA viral load, copies/mL(participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
<400 copies/mL3583343164
≥ 400 copies/mL92703616214
CDC Classification at Study Entry
CDC Classification at Study Entry(participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
C283711884
Not C991162851294
Antiretroviral (ARV) Treatment at Entry
Antiretroviral (ARV) Treatment at Entry(participants)Group 1 (15<CD4%<25)Group 1 (CD4%≥25)Group 2Group 3Total
HAART with PI70812238211
HAART with NNRTI (no PI)143431465
Other ARV681116
No ARV373013686
08

Study locations

37 sites
  • Usc La Nichd Crs
    Alhambra, California 91803, United States
  • Miller Children's Hosp. Long Beach CA NICHD CRS
    Long Beach, California 90806, United States
  • Children's Hospital of Los Angeles NICHD CRS
    Los Angeles, California 90027-6062, United States
  • UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
    Los Angeles, California 90095-1752, United States
  • University of California, UC San Diego CRS
    San Diego, California 92103, United States
  • Univ. of California San Francisco NICHD CRS
    San Francisco, California 94143, United States
  • Harbor UCLA Medical Ctr. NICHD CRS
    Torrance, California 90502, United States
  • Univ. of Colorado Denver NICHD CRS
    Aurora, Colorado 80045, United States
  • Children's National Med. Ctr. Washington DC NICHD CRS
    Washington, District of Columbia 20010, United States
  • Howard Univ. Washington DC NICHD CRS
    Washington, District of Columbia 20060, United States
  • South Florida CDTC Ft Lauderdale NICHD CRS
    Fort Lauderdale, Florida 33316, United States
  • Univ. of Florida Jacksonville NICHD CRS
    Jacksonville, Florida 32209, United States
  • Pediatric Perinatal HIV Clinical Trials Unit CRS
    Miami, Florida 33136, United States
  • USF - Tampa NICHD CRS
    Tampa, Florida 33606, United States
  • Rush Univ. Cook County Hosp. Chicago NICHD CRS
    Chicago, Illinois 60612, United States
  • Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
    Chicago, Illinois 60614, United States
  • Tulane Univ. New Orleans NICHD CRS
    New Orleans, Louisiana 70112, United States
  • Univ. of Maryland Baltimore NICHD CRS
    Baltimore, Maryland 21201, United States
  • Children's Hosp. of Boston NICHD CRS
    Boston, Massachusetts 02115, United States
  • Boston Medical Center Ped. HIV Program NICHD CRS
    Boston, Massachusetts 02118, United States
  • WNE Maternal Pediatric Adolescent AIDS CRS
    Worcester, Massachusetts 01605, United States
  • Children's Hospital of Michigan NICHD CRS
    Detroit, Michigan 48201, United States
  • Rutgers - New Jersey Medical School CRS
    Newark, New Jersey 07103, United States
  • Bronx-Lebanon CRS
    Bronx, New York 10457, United States
  • Jacobi Med. Ctr. Bronx NICHD CRS
    Bronx, New York 10461, United States
  • Nyu Ny Nichd Crs
    New York, New York 10016, United States
  • Metropolitan Hosp. NICHD CRS
    New York, New York 10029, United States
  • Columbia IMPAACT CRS
    New York, New York 10032, United States
  • Strong Memorial Hospital Rochester NY NICHD CRS
    Rochester, New York 14642, United States
  • SUNY Stony Brook NICHD CRS
    Stony Brook, New York 11794, United States
  • DUMC Ped. CRS
    Durham, North Carolina 27710, United States
  • The Children's Hosp. of Philadelphia IMPAACT CRS
    Philadelphia, Pennsylvania 19104, United States
  • St. Jude Children's Research Hospital CRS
    Memphis, Tennessee 38105, United States
  • Texas Children's Hospital CRS
    Houston, Texas 77030, United States
  • Seattle Children's Research Institute CRS
    Seattle, Washington 98105, United States
  • University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
    San Juan, 00935, Puerto Rico
  • San Juan City Hosp. PR NICHD CRS
    San Juan, 00936, Puerto Rico
09

References and documents

Publications

  • Campos-Outcalt D. Meningococcal vaccine: New product, new recommendations. J Fam Pract. 2005 Apr;54(4):324-6. PubMed 15833222 ↗
  • Centers for Disease Control and Prevention (CDC). Update: Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine--United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep. 2006 Oct 20;55(41):1120-4. Erratum In: MMWR Morb Mortal Wkly Rep. 2006 Nov 3;55(43):1177. PubMed 17060898 ↗
  • Keyserling H, Papa T, Koranyi K, Ryall R, Bassily E, Bybel MJ, Sullivan K, Gilmet G, Reinhardt A. Safety, immunogenicity, and immune memory of a novel meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV-4) in healthy adolescents. Arch Pediatr Adolesc Med. 2005 Oct;159(10):907-13. doi: 10.1001/archpedi.159.10.907. PubMed 16203934 ↗
  • Mehlhorn AJ, Balcer HE, Sucher BJ. Update on prevention of meningococcal disease: focus on tetravalent meningococcal conjugate vaccine. Ann Pharmacother. 2006 Apr;40(4):666-73. doi: 10.1345/aph.1G486. Epub 2006 Mar 7. PubMed 16595570 ↗
  • Platonov AE, Vershinina IV, Kuijper EJ, Borrow R, Kayhty H. Long term effects of vaccination of patients deficient in a late complement component with a tetravalent meningococcal polysaccharide vaccine. Vaccine. 2003 Oct 1;21(27-30):4437-47. doi: 10.1016/s0264-410x(03)00440-7. PubMed 14505927 ↗
  • Pearson IC, Baker R, Sullivan AK, Nelson MR, Gazzard BG. Meningococcal infection in patients with the human immunodeficiency virus and acquired immunodeficiency syndrome. Int J STD AIDS. 2001 Jun;12(6):410-1. doi: 10.1258/0956462011923237. PubMed 11368827 ↗
  • Siberry GK, Williams PL, Lujan-Zilbermann J, Warshaw MG, Spector SA, Decker MD, Heckman BE, Demske EF, Read JS, Jean-Philippe P, Kabat W, Nachman S; IMPAACT P1065 Protocol Team. Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents. Pediatr Infect Dis J. 2010 May;29(5):391-6. doi: 10.1097/INF.0b013e3181c38f3b. PubMed 20431379 ↗
  • Spector SA, Qin M, Lujan-Zilbermann J, Singh KK, Warshaw MG, Williams PL, Jean-Philippe P, Fenton T, Siberry GK; IMPAACT P1065 Protocol Team. Genetic variants in toll-like receptor 2 (TLR2), TLR4, TLR9, and FCgamma receptor II are associated with antibody response to quadrivalent meningococcal conjugate vaccine in HIV-infected youth. Clin Vaccine Immunol. 2013 Jun;20(6):900-6. doi: 10.1128/CVI.00042-13. Epub 2013 Apr 17. PubMed 23595505 ↗
  • Lujan-Zilbermann J, Warshaw MG, Williams PL, Spector SA, Decker MD, Abzug MJ, Heckman B, Manzella A, Kabat B, Jean-Philippe P, Nachman S, Siberry GK; International Maternal Pediatric Adolescent AIDS Clinical Trials Group P1065 Protocol Team. Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus. J Pediatr. 2012 Oct;161(4):676-81.e2. doi: 10.1016/j.jpeds.2012.04.005. Epub 2012 May 22. PubMed 22622049 ↗
  • Siberry GK, Warshaw MG, Williams PL, Spector SA, Decker MD, Jean-Philippe P, Yogev R, Heckman BE, Manzella A, Roa J, Nachman S, Lujan-Zilbermann J; IMPAACT P1065 Protocol Team. Safety and immunogenicity of quadrivalent meningococcal conjugate vaccine in 2- to 10-year-old human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2012 Jan;31(1):47-52. doi: 10.1097/INF.0b013e318236c67b. PubMed 21987006 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 3, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00459316
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Responsible party
Sponsor
First posted
Apr 11, 2007
Start date
Jun 2007
Primary completion
Mar 2013
Completion
Mar 2013
Results posted
May 12, 2014
Last update
Nov 3, 2021

Study contacts

George K. Siberry, MD, MPH
study chair · Pediatric, Adolescent, and Maternal AIDS (PAMA) Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Jorge Lujan-Zilbermann, MD, MS
study chair · Division of Infectious Diseases, Department of Pediatrics, University of South Florida College of Medicine
View the source record on ClinicalTrials.gov ↗

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