A Double-Blind Placebo-Controlled Trial of the Safety and Immunogenicity of a Seven Valent Pneumococcal Conjugate Vaccine in Presumed HIV-Infected Infants

This study has been completed.
Sponsor:
Collaborator:
Lederle-Praxis Biologicals
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000829
First received: November 2, 1999
Last updated: May 8, 2012
Last verified: May 2012
  Purpose

To assess whether HIV-infected infants who receive a heptavalent pneumococcal conjugate vaccine have more local reactions at the site of injection and systemic reactions than placebo subjects. To assess whether this vaccine is more immunogenic than placebo following the third vaccination.

Children with HIV infection are at increased risk for invasive pneumococcal infection, particularly bacteremia. A large proportion of pneumococcal disease is caused by a limited number of serotypes. The maximum number of pneumococcal serotypes that can be included in a new conjugate vaccine is felt to be limited by the amount of carrier protein. A heptavalent pneumococcal conjugate vaccine has been developed that consists of pneumococcal capsular saccharides from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F bound to a diphtheria toxin mutant carrier protein.


Condition Intervention Phase
HIV Infections
Pneumococcal Infections
Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
Biological: Pneumococcal Conjugate Vaccine, Heptavalent
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Double-Blind Placebo-Controlled Trial of the Safety and Immunogenicity of a Seven Valent Pneumococcal Conjugate Vaccine in Presumed HIV-Infected Infants

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Comparison of adverse reactions between PCV and placebo patients that occur within 48 hours after each injection [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Comparison of seroconversion rates and changes in (IgG) ELISA antibody levels between PCV and placebo patients after the primary series [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of booster rates in serum ELISA (IgG) antibody levels just before the 4th vaccination and one month after the 4th vaccination in children receiving PCV and placebo [ Time Frame: Prior to 4th vaccination and at 1 month after 4th vaccination ] [ Designated as safety issue: No ]
  • Comparison of serum IgG1 and IgG2 subclass and IgA type specific seroconversion rates and changes in antibody levels in response to the primary immunization series and booster vaccination between PCV and placebo patients [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To compare the decline of serum total IgG, IgG1, IgG2, and IgA pneumococcal type specific antibody after the 3rd and after the 4th vaccination in PCV versus placebo patients [ Time Frame: At a time after the 3rd vaccination and at a time after the 4th vaccination ] [ Designated as safety issue: No ]
  • Modeling of the rates of seroconversion and changes in serum antibody levels in PCV patients, after the primary series and booster series, to clinical HIV staging and T-lymphocyte parameters, as well as B-lymphocyte parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Completion Date: October 1999
Arms Assigned Interventions
Experimental: 1
Patients receiving intramuscular heptavalent pneumococcal conjugate vaccine
Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
Administered as an injection at 24 months of age
Biological: Pneumococcal Conjugate Vaccine, Heptavalent
Administered as an injection at 0, 2, 4, and 15 months of age
Placebo Comparator: 2
Patients receiving placebo vaccine
Biological: Pneumococcal Vaccine, Polyvalent (23-valent)
Administered as an injection at 24 months of age
Biological: Placebo
Administered at 0, 2, 4, and 15 months of age

Detailed Description:

Children with HIV infection are at increased risk for invasive pneumococcal infection, particularly bacteremia. A large proportion of pneumococcal disease is caused by a limited number of serotypes. The maximum number of pneumococcal serotypes that can be included in a new conjugate vaccine is felt to be limited by the amount of carrier protein. A heptavalent pneumococcal conjugate vaccine has been developed that consists of pneumococcal capsular saccharides from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F bound to a diphtheria toxin mutant carrier protein.

Infants are randomized to receive either heptavalent pneumococcal conjugate vaccine or placebo by intramuscular injection at study months 0, 2, and 4, and then at 15 months of age. Additionally, patients receive PNU-IMUNE 23 ( pneumococcal polyvalent vaccine ) at 24 months of age.

  Eligibility

Ages Eligible for Study:   2 Months to 6 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Antipyretics for rectal temperature >= 100.4 F.
  • Antiretroviral therapy.

Patients must have:

  • HIV positivity.
  • Birth weight at least 1800 g (3.75 lb).
  • Consent and compliance of parent or guardian.

NOTE:

  • Coenrollment in other therapeutic protocols (except ACTG 218, 230, and 279) is permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Enrollment in HIV vaccine trials.
  • Major congenital anomalies that are incapacitating, result in immunologic abnormalities, or require major surgical procedures.
  • Congenital immunoglobulin deficiency, SS or SC hemoglobinopathy, or asplenia.
  • Hypogammaglobulinemia.

Concurrent Medication:

Excluded:

  • Prophylactic antipyretics.

Patients with the following prior conditions are excluded:

Acute moderate to severe intercurrent illness or fever within 72 hours prior to study entry.

Prior Medication:

Excluded:

  • Any prior pneumococcal vaccine.
  • Measles vaccine within 1 month prior to study vaccination.
  • Any other routine vaccine within 1 week prior to study vaccination.
  • Any immunosuppressant agent, including prednisone, for more than 6 weeks.

Prior Treatment:

Excluded:

  • Blood products within 56 days prior to study vaccination.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000829

  Show 33 Study Locations
Sponsors and Collaborators
Lederle-Praxis Biologicals
Investigators
Study Chair: James King, Jr, M.D. University of Maryland
Study Chair: Sharon Nachman, M.D. SUNY at Stony Brook
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000829     History of Changes
Other Study ID Numbers: ACTG 292, 11268
Study First Received: November 2, 1999
Last Updated: May 8, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Pneumococcal Infections
Bacterial Vaccines

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumococcal Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 24, 2014