HIV InfectionsPhase 1/2NCT00459316

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

A Phase 1/2 study testing Quadrivalent meningococcal conjugate vaccine in people with HIV Infections and Meningitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 37 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 2 to 24 years
Conditions the study is for: HIV Infections, Meningitis
What is being tested?: Quadrivalent meningococcal conjugate vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 384 participants
Where: 37 sitesin 2 countries
Study dates: Jun 2007to Mar 2013
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 24 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

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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

Who cannot join

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

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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

Trial locations and contacts

37 sites in 2 countries.

Country

City, postcode or hospital

37 sites in 2 countries

United States35 sites

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

Other trials in United States

Puerto Rico2 sites

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, 00935
San Juan City Hosp. PR NICHD CRS
San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: Phase I/II Study of Safety and Immunogenicity of Quadrivalent Meningococcal Conjugate Vaccine (MCV4) in HIV-Infected Children and Youth And Open Label Immunogenicity Study of a Booster Dose of MCV4 in Previously Immunized HIV-Infected Children and Youth

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.

Conditions: HIV Infections, Meningitis
Being tested: Quadrivalent meningococcal conjugate vaccine
Medical subject headings: HIV Infections, Meningitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Quadrivalent meningococcal conjugate vaccineBiological
Also called MCV4
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.

Study groups in NCT00459316
Study group	Role	What they receive
Group 1	Experimental	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. Receives: Biological: Quadrivalent meningococcal conjugate vaccine
Group 2	Experimental	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. Receives: Biological: Quadrivalent meningococcal conjugate vaccine
Group 3	Experimental	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. Receives: Biological: Quadrivalent meningococcal conjugate vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Study entry and Week 28
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.
Measured: At Study entry, Week 4
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.
Measured: Week 72
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.
Measured: From administration of Dose 1 at week 0 to 42 days post-vaccination
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.
Measured: From administration of Dose 2 at week 24 to 6 weeks post-vaccination
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)
Measured: At 3.5 years (Step 3 entry)
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.
Measured: Step 3 entry and Week 1 post-booster vaccine
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.
Measured: Step 3 entry and Week 1 post-booster vaccine
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.
Measured: Step 3 entry and Week 4 post-booster vaccine
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)
Measured: At Step 3 Weeks 4 and 24 post-booster vaccine

Secondary outcomes (5)

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)
Measured: At Weeks 4, 28, and 72
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
Measured: At 3.5 years
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.
Measured: At Week 1 post-booster vaccination
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.
Measured: At Week 4 post-booster vaccination
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.
Measured: From administration of vaccination at Step 3 entry through 6 weeks post-vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2007Mar 2013

First posted11 Apr 2007 (estimated)
Study startJun 2007
Primary completionMar 2013
Study completionMar 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 384 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00459316
Sponsor's protocol ID: P1065
Other IDs: 10396, IMPAACT P1065, PACTG P1065
Status last verified: Oct 2021
First submitted: 10 Apr 2007
Last updated: 3 Nov 2021
Results posted: Yes, on ClinicalTrials.gov

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.
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Study of Safety and Immunogenicity of Quadrivalent Meningococcal Conjugate Vaccine (MCV4) in HIV-Infected Children and Youth And Open Label Immunogenicity Study of a Booster Dose of MCV4 in Previously Immunized HIV-Infected Children and Youth
ClinicalTrials.gov ID: NCT00459316
Acronym / sponsor ID: P1065
Conditions: HIV Infections, Meningitis
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 384 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Study start: Jun 2007
Primary completion: Mar 2013 (actual)
Study completion: Mar 2013 (actual)
First posted: 11 Apr 2007 (estimated)
Results: Posted 12 May 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Group 1	Experimental	Biological: Quadrivalent meningococcal conjugate vaccineParticipants ≤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.
Group 2	Experimental	Biological: Quadrivalent meningococcal conjugate vaccineParticipants ≤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.
Group 3	Experimental	Biological: Quadrivalent meningococcal conjugate vaccineParticipants >=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.

Who may qualify

Ages: 2 to 24 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (54 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Quadrivalent meningococcal conjugate vaccineAlso: MCV4MCV4 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.	Biological	Group 1, Group 2, Group 3

Primary outcome

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
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.
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
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.
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72
Time frame: Week 72
Protective levels of antibody are titers ≥1:128.
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
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.
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
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.
Number of Participants With Immunogenicity at Step 3 Entry
Time frame: At 3.5 years (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)
Number of Participants With 4-fold Memory Response in Step 3
Time frame: Step 3 entry and Week 1 post-booster vaccine
Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.
Number of Participants With Seropositive Memory Response (in Step 3)
Time frame: Step 3 entry and Week 1 post-booster vaccine
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.
Number of Participants With Primary Response (in Step 3)
Time frame: Step 3 entry and Week 4 post-booster vaccine
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.
Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24
Time frame: At Step 3 Weeks 4 and 24 post-booster vaccine
Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)

5 secondary outcomes

Immunogenic Response to Serogroup C in Group 2
Time frame: At Weeks 4, 28, and 72
Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry
Time frame: At 3.5 years
Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)
Time frame: At Week 1 post-booster vaccination
Immunologic Memory or Primary Response for Serogroup C by Treatment Arm
Time frame: At Week 4 post-booster vaccination
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

Results and safety

Results posted to the registry on 12 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: CD4%≥15, Age ≤11 to <25	280	259
Group 2: CD4%<15, Age ≤11 to <25	39	32
Group 3: Age ≥2 to <11, CD4%≥25	59	57

Primary outcome: 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. Number. Unit: participants

Measure	Group 1 (15<CD4%<25) n = 49	Group 1 (CD4%≥25) n = 66	Group 2 n = 20	Group 3 n = 49
Week 28 reponders, serogroup A	27 (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 C	28 (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-135	36 (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 Y	32 (0.62 to 0.88)	54 (0.83 to 0.97)	1 (0.001 to 0.25)	41 (0.70 to 0.93)

Population analysed: This outcome only includes participants who received 2 doses and had antibody data from both entry and Week 28.The number of participants analyzed for Group 1 (15\<CD4%\<25), Group 1 (CD4%≥25), Group 2, Group 3 are respectively: serogroup A: 49, 63, 20, 49 serogroup C: 47, 65, 18, 49 serogroup W-135: 47, 66, 19, 49 serogroup Y: 49, 66, 19, 49

Primary outcome: 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. Number. Unit: participants

Measure	Group 1 (15<CD4%<25) n = 93	Group 1 (CD4%≥25) n = 131	Group 2 n = 20	Group 3 n = 49
Week 4 Seroconverters, serogroup A	61	107	5	45
Week 4 Seroconverters, serogroup C	44	89	3	21
Week 4 Seroconverters, serogroup W-135	66	118	6	48
Week 4 Seroconverters, serogroup Y	49	100	8	37

Population analysed: This outcome only includes participants who had antibody data from both entry and Week 4.The number of participants analyzed for Group 1 (15\<CD4%\<25), Group 1 (CD4%≥25), Group 2, Group 3 respectively are: serogroup A are 93, 129, 20, 49 serogroup C are 90, 130, 18, 49 serogroup W-135 are 91, 131, 19, 49 serogroup Y are 93, 131, 20, 49

Primary outcome: Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72

Time frame: Week 72. Number. Unit: participants

Measure	Group 1 (15<CD4%<25) n = 82	Group 1 (CD4%≥25) n = 110	Group 2 n = 18	Group 3 n = 44
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

Population analysed: 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

Primary outcome: 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. Number. Unit: participants

Measure	Group 1 (15<CD4%<25) n = 127	Group 1 (CD4%≥25) n = 153	Group 2 n = 39	Group 3 n = 59
Value	3	1	3	0

Group 1 (15<CD4%<25) vs Group 1 (CD4%≥25) vs Group 2: p = 0.03, Fisher Exact

Population analysed: All participants who received Dose 1.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From study entry through Step 3, week 24 (4 years ). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1 (15<CD4%≤25)	4 of 127 (3.1%)	94 of 127 (74%)	Not reported
Group 1 (CD4%≥25)	5 of 153 (3.3%)	113 of 153 (73.9%)	Not reported
Group 2	5 of 39 (12.8%)	33 of 39 (84.6%)	Not reported
Group 3	2 of 59 (3.4%)	47 of 59 (79.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 15833222Campos-Outcalt D. Meningococcal vaccine: New product, new recommendations. J Fam Pract. 2005 Apr;54(4):324-6.
Background: PubMed 17060898Centers 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.
Background: PubMed 16203934Keyserling 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.
Background: PubMed 16595570Mehlhorn 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.
Background: PubMed 14505927Platonov 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.
Background: PubMed 11368827Pearson 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.
Results publication: PubMed 20431379Siberry 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.
Results publication: PubMed 23595505Spector 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.
Results publication: PubMed 22622049Lujan-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.
Results publication: PubMed 21987006Siberry 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

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

37 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 54 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00459316, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2021.