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

This study has been completed.
Sponsor:
Collaborator:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00459316
First received: April 10, 2007
Last updated: January 12, 2016
Last verified: January 2016
Results First Received: March 3, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: HIV Infections
Meningitis
Intervention: Biological: Quadrivalent meningococcal conjugate vaccine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Group 1: CD4%≥15, Age ≤11 to <25

Participants ≤11 to <25 years of age with CD4% at screening ≥15%; All receiving Quadrivalent meningococcal conjugate vaccine at entry, those who were eligible/randomized receiving Quadrivalent meningococcal conjugate vaccine at week 24, and 3 years.

Quadrivalent 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 two times for each participant, depending on adverse reactions.

Group 2: CD4%<15, Age ≤11 to <25

Participants ≤11 to <25 years of age with CD4% at screening <15%; All receiving Quadrivalent meningococcal conjugate vaccine at entry, those who were eligible receiving Quadrivalent meningococcal conjugate vaccine at week 24.

Quadrivalent 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 two times for each participant, depending on adverse reactions.

Group 3: Age ≥2 to <11, CD4%≥25

Participants ≥2 to <11 years of age with CD4% at screening ≥ 25%; All receiving Quadrivalent meningococcal conjugate vaccine at entry, those who were eligible receiving Quadrivalent meningococcal conjugate vaccine at week 24, and 3 years.

Quadrivalent 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 two times for each participant, depending on adverse reactions.


Participant Flow for 2 periods

Period 1:   Steps 1 & 2
    Group 1: CD4%≥15, Age ≤11 to <25   Group 2: CD4%<15, Age ≤11 to <25   Group 3: Age ≥2 to <11, CD4%≥25
STARTED   280   39   59 
COMPLETED   259   32   57 
NOT COMPLETED   21   7   2 
Other eligibility failure                1                1                0 
Death                1                1                0 
Not able to get to clinic                7                4                0 
Withdrawal by Subject                6                1                0 
Not willing to adhere to regulations                1                0                0 
Lost to Follow-up                5                0                2 

Period 2:   Step 3
    Group 1: CD4%≥15, Age ≤11 to <25   Group 2: CD4%<15, Age ≤11 to <25   Group 3: Age ≥2 to <11, CD4%≥25
STARTED   152 [1]   0 [2]   40 [1] 
COMPLETED   149   0   39 
NOT COMPLETED   3   0   1 
Withdrawal by Subject                3                0                1 
[1] Not all participants from Steps 1/2 were eligible for Step 3
[2] Group 2 participants were not eligible for Step 3



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who started study treatment.

Reporting Groups
  Description
Group 1 (15<CD4%<25) Participants ≥11 to <25 years with 15<CD4%<25
Group 1 (CD4%≥25) Participants ≥11 to <25 years with CD4%≥25
Group 2 Participants ≥11 to <25 years with CD4%<15
Group 3 Participants ≥ 2 to <11 years with CD4% ≥25
Total Total of all reporting groups

Baseline Measures
   Group 1 (15<CD4%<25)   Group 1 (CD4%≥25)   Group 2   Group 3   Total 
Overall Participants Analyzed 
[Units: Participants]
 127   153   39   59   378 
Age 
[Units: Years]
Median (Full Range)
 18 
 (11 to 24) 
 16 
 (11 to 24) 
 20 
 (14 to 24) 
 6 
 (2 to 10) 
 16 
 (2 to 24) 
Gender 
[Units: Participants]
         
Female   44   70   16   31   161 
Male   83   83   23   28   217 
Race 
[Units: Participants]
         
Asian   1   1   0   2   4 
Native Hawaiian or other Pacific islander   1   0   0   1   2 
Black or African American   72   69   22   34   197 
White   47   75   14   21   157 
American Indian   2   3   0   0   5 
More than One race   0   3   2   0   5 
Unknown   4   2   1   1   8 
Ethnicity 
[Units: Participants]
         
Hispanic or Latino   44   61   16   18   139 
Not Hispanic or Latino   83   89   23   40   235 
Unknown   0   3   0   1   4 
Screening CD4% 
[Units: Percent]
Median (Full Range)
 20.0 
 (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 
[Units: Participants]
         
<400 copies/mL   35   83   3   43   164 
≥ 400 copies/mL   92   70   36   16   214 
CDC Classification at Study Entry 
[Units: Participants]
         
 28   37   11   8   84 
Not C   99   116   28   51   294 
Antiretroviral (ARV) Treatment at Entry 
[Units: Participants]
         
HAART with PI   70   81   22   38   211 
HAART with NNRTI (no PI)   14   34   3   14   65 
Other ARV   6   8   1   1   16 
No ARV   37   30   13   6   86 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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.   [ Time Frame: Study entry and Week 28 ]

2.  Primary:   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)   [ Time Frame: At Study entry, Week 4 ]

3.  Primary:   Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72   [ Time Frame: Week 72 ]

4.  Primary:   Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.   [ Time Frame: From administration of Dose 1 at week 0 to 42 days post-vaccination ]

5.  Primary:   Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.   [ Time Frame: From administration of Dose 2 at week 24 to 6 weeks post-vaccination ]

6.  Primary:   Number of Participants With Immunogenicity at Step 3 Entry   [ Time Frame: At 3.5 years (Step 3 entry) ]

7.  Primary:   Number of Participants With 4-fold Memory Response in Step 3   [ Time Frame: Step 3 entry and Week 1 post-booster vaccine ]

8.  Primary:   Number of Participants With Seropositive Memory Response (in Step 3)   [ Time Frame: Step 3 entry and Week 1 post-booster vaccine ]
  Hide Outcome Measure 8

Measure Type Primary
Measure Title Number of Participants With Seropositive Memory Response (in Step 3)
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Because response is a combination of memory and primary response, only participants with data for weeks 0, 1 and 4 are included.

Reporting Groups
  Description
Group 1A Participants ≥11 to <25 years with CD4%>15, 1 dose MCV4 vaccine
Group 1B Participants ≥11 to <25 years with CD4%>15, 2 doses MCV4 vaccine
Group 3 Participants ≥ 2 to <11 years with CD4% ≥25

Measured Values
   Group 1A   Group 1B   Group 3 
Participants Analyzed 
[Units: Participants]
 73   65   36 
Number of Participants With Seropositive Memory Response (in Step 3) 
[Units: Participants]
     
Seropositive memory responder, serogroup A   65   61   35 
Seropositive memory responder, serogroup C   62   55   34 
Seropositive memory responder, serogroup W-135   65   60   34 
Seropositive memory responder, serogroup Y   67   57   33 

No statistical analysis provided for Number of Participants With Seropositive Memory Response (in Step 3)



9.  Primary:   Number of Participants With Primary Response (in Step 3)   [ Time Frame: Step 3 entry and Week 4 post-booster vaccine ]

10.  Primary:   Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24   [ Time Frame: At Step 3 Weeks 4 and 24 post-booster vaccine ]

11.  Secondary:   Immunogenic Response to Serogroup C in Group 2   [ Time Frame: At Weeks 4, 28, and 72 ]

12.  Secondary:   Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry   [ Time Frame: At 3.5 years ]

13.  Secondary:   Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)   [ Time Frame: At Week 1 post-booster vaccination ]

14.  Secondary:   Immunologic Memory or Primary Response for Serogroup C by Treatment Arm   [ Time Frame: At Week 4 post-booster vaccination ]

15.  Secondary:   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.   [ Time Frame: From administration of vaccination at Step 3 entry through 6 weeks post-vaccination ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
phone: (919) 405-1429
e-mail: mallen@fhi360.org


Publications of Results:

Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00459316     History of Changes
Other Study ID Numbers: P1065
10396 ( Registry Identifier: DAIDS ES Registry Number )
IMPAACT P1065
PACTG P1065
Study First Received: April 10, 2007
Results First Received: March 3, 2014
Last Updated: January 12, 2016
Health Authority: United States: Food and Drug Administration