Safety of and Immune Response to a Meningitis Vaccine in HIV-Infected Children and Youth
NCT ID: NCT00459316
Last Updated: 2021-11-03
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
384 participants
INTERVENTIONAL
2007-06-30
2013-03-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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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.
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 three times for each participant, depending on adverse reactions.
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.
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 three times for each participant, depending on adverse reactions.
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.
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 three times for each participant, depending on adverse reactions.
Interventions
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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 three times for each participant, depending on adverse reactions.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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)
* 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
* 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
* 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.
* 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
2 Years
24 Years
ALL
No
Sponsors
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International Maternal Pediatric Adolescent AIDS Clinical Trials Group
NETWORK
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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George K. Siberry, MD, MPH
Role: 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
Role: STUDY_CHAIR
Division of Infectious Diseases, Department of Pediatrics, University of South Florida College of Medicine
Locations
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Usc La Nichd Crs
Alhambra, California, United States
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, United States
Children's Hospital of Los Angeles NICHD CRS
Los Angeles, California, United States
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
Los Angeles, California, United States
University of California, UC San Diego CRS
San Diego, California, United States
Univ. of California San Francisco NICHD CRS
San Francisco, California, United States
Harbor UCLA Medical Ctr. NICHD CRS
Torrance, California, United States
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, United States
Children's National Med. Ctr. Washington DC NICHD CRS
Washington D.C., District of Columbia, United States
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, United States
South Florida CDTC Ft Lauderdale NICHD CRS
Fort Lauderdale, Florida, United States
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, United States
USF - Tampa NICHD CRS
Tampa, Florida, United States
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States
Tulane Univ. New Orleans NICHD CRS
New Orleans, Louisiana, United States
Univ. of Maryland Baltimore NICHD CRS
Baltimore, Maryland, United States
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, United States
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, United States
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States
Children's Hospital of Michigan NICHD CRS
Detroit, Michigan, United States
Rutgers - New Jersey Medical School CRS
Newark, New Jersey, United States
Nyu Ny Nichd Crs
New York, New York, United States
Metropolitan Hosp. NICHD CRS
New York, New York, United States
Columbia IMPAACT CRS
New York, New York, United States
Strong Memorial Hospital Rochester NY NICHD CRS
Rochester, New York, United States
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States
Bronx-Lebanon CRS
The Bronx, New York, United States
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, United States
DUMC Ped. CRS
Durham, North Carolina, United States
The Children's Hosp. of Philadelphia IMPAACT CRS
Philadelphia, Pennsylvania, United States
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States
Texas Children's Hospital CRS
Houston, Texas, United States
Seattle Children's Research Institute CRS
Seattle, Washington, United States
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, , Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, , Puerto Rico
Countries
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References
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Campos-Outcalt D. Meningococcal vaccine: New product, new recommendations. J Fam Pract. 2005 Apr;54(4):324-6.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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10396
Identifier Type: REGISTRY
Identifier Source: secondary_id
IMPAACT P1065
Identifier Type: -
Identifier Source: secondary_id
PACTG P1065
Identifier Type: -
Identifier Source: secondary_id
P1065
Identifier Type: -
Identifier Source: org_study_id