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

NCT00459316 | Completed Phase 1 Results

• 4 other identifiers: P106510396IMPAACT P1065PACTG P1065
• Study Type: interventional
• Target: 384
• Locations: 2 countries
• Sites: 37

Brief 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.

Conditions

HIV Infections; Meningitis

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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)

  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.

  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.

  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.

  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)

  At Step 3 Weeks 4 and 24 post-booster vaccine

Secondary Outcomes (5)

• Immunogenic Response to Serogroup C in Group 2

  At Weeks 4, 28, and 72

• Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry

  At 3.5 years

• Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)

  At Week 1 post-booster vaccination

• Immunologic Memory or Primary Response for Serogroup C by Treatment Arm

  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.

  From administration of vaccination at Step 3 entry through 6 weeks post-vaccination

Study Arms (3)

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.

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.

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.

Biological: Quadrivalent meningococcal conjugate vaccine

Interventions

Quadrivalent meningococcal conjugate vaccine BIOLOGICAL

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.

Also known as: MCV4

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 2 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: collaborator

Study Sites (37)

Usc La Nichd Crs

Alhambra, California, 91803, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

Children's Hospital of Los Angeles NICHD CRS

Los Angeles, California, 90027-6062, United States

Location

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, 90095-1752, United States

Location

University of California, UC San Diego CRS

San Diego, California, 92103, United States

Location

Univ. of California San Francisco NICHD CRS

San Francisco, California, 94143, United States

Location

Harbor UCLA Medical Ctr. NICHD CRS

Torrance, California, 90502, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Children's National Med. Ctr. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20010, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, 33136, United States

Location

USF - Tampa NICHD CRS

Tampa, Florida, 33606, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, 60614, United States

Location

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, 70112, United States

Location

Univ. of Maryland Baltimore NICHD CRS

Baltimore, Maryland, 21201, United States

Location

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, 01605, United States

Location

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, 48201, United States

Location

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, 07103, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Metropolitan Hosp. NICHD CRS

New York, New York, 10029, United States

Location

Columbia IMPAACT CRS

New York, New York, 10032, United States

Location

Strong Memorial Hospital Rochester NY NICHD CRS

Rochester, New York, 14642, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794, United States

Location

Bronx-Lebanon CRS

The Bronx, New York, 10457, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

DUMC Ped. CRS

Durham, North Carolina, 27710, United States

Location

The Children's Hosp. of Philadelphia IMPAACT CRS

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital CRS

Houston, Texas, 77030, United States

Location

Seattle Children's Research Institute CRS

Seattle, Washington, 98105, United States

Location

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Related Publications (10)

• Campos-Outcalt D. Meningococcal vaccine: New product, new recommendations. J Fam Pract. 2005 Apr;54(4):324-6.

  PMID: 15833222 BACKGROUND

• 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.

  PMID: 17060898 BACKGROUND

• 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.

  PMID: 16203934 BACKGROUND

• 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.

  PMID: 16595570 BACKGROUND

• 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.

  PMID: 14505927 BACKGROUND

• 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.

  PMID: 11368827 BACKGROUND

• 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.

  PMID: 20431379 RESULT

• 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.

  PMID: 23595505 RESULT

• 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.

  PMID: 22622049 RESULT

• 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.

  PMID: 21987006 RESULT

MeSH Terms

Conditions

HIV Infections; Meningitis

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neuroinflammatory Diseases; Nervous System Diseases

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• George K. Siberry, MD, MPH

  Pediatric, Adolescent, and Maternal AIDS (PAMA) Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

  STUDY CHAIR

• Jorge Lujan-Zilbermann, MD, MS

  Division of Infectious Diseases, Department of Pediatrics, University of South Florida College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2007
• First Posted: April 11, 2007
• Study Start: June 1, 2007
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: November 3, 2021
• Results First Posted: May 12, 2014

Record last verified: 2021-10

Locations

US (35); PR (2)