Phase 2 N=378 Randomized Prevention

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

HIV Infections · Meningitis

Bottom Line

View on ClinicalTrials.gov: NCT00459316 ↗

Enrolled (actual)

378

Serious AEs

4.2%

Results posted

May 2014

Primary outcome: 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. — 27; 60; 8; 43 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Quadrivalent meningococcal conjugate vaccine (Biological)
Age: Pediatric, Adult · 2+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Mar 2013

Outcome Measures

Outcome	Result	p-value
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.	27; 60; 8; 43; 28; 49	—
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)	61; 107; 5; 45; 44; 89	—
PRIMARY Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72	39; 82; 4; 35; 17; 36	—
PRIMARY Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.	3; 1; 3; 0	0.03 sig
PRIMARY Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.	0; 0; 2; 0	0.01 sig
PRIMARY Number of Participants With Immunogenicity at Step 3 Entry	47; 48; 34; 19; 20; 9	—
PRIMARY Number of Participants With 4-fold Memory Response in Step 3	54; 49; 33; 56; 50; 34	—
PRIMARY Number of Participants With Seropositive Memory Response (in Step 3)	65; 61; 35; 62; 55; 34	—
PRIMARY Number of Participants With Primary Response (in Step 3)	2; 2; 0; 1; 1; 1	—
PRIMARY Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24	66; 67; 37; 61; 60; 35	—
SECONDARY Immunogenic Response to Serogroup C in Group 2	4; 4; 1	—
SECONDARY Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry	19; 17; 3; 6	—
SECONDARY Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)	65; 61	—
SECONDARY Immunologic Memory or Primary Response for Serogroup C by Treatment Arm	64; 57	—
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.	2; 0	—

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.

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

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Data sourced from ClinicalTrials.gov (NCT00459316). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.