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: August 12, 2014
Last verified: August 2014
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  
Number of Participants  
[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]
         
C     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 ]
  Hide Outcome Measure 3

Measure Type Primary
Measure Title Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72
Measure Description Protective levels of antibody are titers ≥1:128.
Time Frame Week 72  
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.

Participants with antibody data at Week 72. The number of Participants analyzed for Group 1 (15<CD4%<25), Group 1 (CD4%≥25), Group 2, Group 3 respectively are:

serogroup A are 82, 108, 18, 44 serogroup C are 78, 110, 16, 44 serogroup W-135 are 80, 110, 17, 44 serogroup Y are 82, 110, 18, 44


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

Measured Values
    Group 1 (15<CD4%<25)     Group 1 (CD4%≥25)     Group 2     Group 3  
Number of Participants Analyzed  
[units: participants]
  82     110     18     44  
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72  
[units: participants]
       
Week 72 Responders, serogroup A     39     82     4     35  
Week 72 Responders, serogroup C     17     36     1     20  
Week 72 Responders, serogroup W-135     36     83     6     42  
Week 72 Responders, serogroup Y     49     80     5     40  

No statistical analysis provided for Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at 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 ]

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:   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 ]

12.  Secondary:   To Examine Whether the Immunogenicity of the MCV4 in HIV-1 Infected Youth Varies as a Function of the Study Subjects’ Immune Status at the Time of Vaccination;   [ Time Frame: Week 4 ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

13.  Secondary:   To Compare the Long-term Immunogenicity, as Assessed by Number of Participants With Protective Antibody Titers (>= 1:128), Between the 1-dose Versus 2-dose Arms for Those in Group 1   [ Time Frame: At Week 72 ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

14.  Secondary:   Immunogenic Response as Assessed by Number of Participants With Protective Antibody Titers (>= 1:128) to Serogroup C in Group 2   [ Time Frame: At Weeks 4, 28, and 72 ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

15.  Secondary:   Comparison of Responders and Non-responders by Genetic Determinants   [ Time Frame: At Weeks 4, 24, 28, and 72 ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

16.  Secondary:   Comparison of the Number of Participants With Protective Antibody Titers for Serogroup C Between Treatment Arms (1 vs. 2 Doses) of Group 1 (Step 3)   [ Time Frame: At 3.5 years ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

17.  Secondary:   Comparison of Memory Response for Serogroup C Between Treatment Arms (1 vs. 2 Doses) of Group 1 (Step 3)   [ Time Frame: At Week 1 post-booster vaccination ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

18.  Secondary:   Comparison of Response (Memory or Primary) for Serogroup C Between Treatment Arms (1 vs. 2 Doses) of Group 1 (Step 3)   [ Time Frame: At Week 4 post-booster vaccination ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No

19.  Secondary:   Comparison of Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody (Titers Great Than or Equal to 1:128), Between Treatment Arms (1 vs. 2 Doses) of Group 1 (Step 3)   [ Time Frame: At Weeks 4 and 24 post-booster vaccination ]
Results not yet posted.   Anticipated Posting Date:   09/2014   Safety Issue:   No


  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: Clinicaltrals.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


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, IMPAACT P1065, PACTG P1065
Study First Received: April 10, 2007
Results First Received: March 3, 2014
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration