Immune Response to Toll-Like Receptor 9-Agonist Adjuvanted Pneumococcal Vaccination in HIV Infected Adults

NCT ID: NCT00562939

Last Updated: 2009-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2009-01-31

Brief Summary

The purpose of this study is to determine whether TLR-9 adjuvanted pneumococcal is more immunogenic than pneumococcal vaccination alone in HIV-infected adults.

Detailed Description

Pneumococcal disease is a major source of morbidity and mortality in HIV-patients. HIV-patients are vaccine hyporesponders. A good immune response to pneumococcal vaccination enhances vaccine effectiveness, thereby preventing the morbidity and mortality caused by pneumococcal disease. Even when an optimized regimen containing both conjugated and polysaccharide pneumococcal vaccine is used, only 13% of the immunized HIV patients are high responders at week 96. Recent data indicate that TLR9-agonists have excellent vaccine adjuvant potential and are safe to use in immunocompetent as well as immunocompromised individuals. The aim of this study is to evaluate the qualitative and quantitive immune response to pneumococcal vaccination with or without TLR9-agonist in HIV-infected adults

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

A

1 mg CpG 7909 + pneumococcal vaccines

Group Type: EXPERIMENTAL

Pneumococcal vaccines + CPG 7909

Intervention Type: BIOLOGICAL

Day 0: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 90: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 270: 0.5 ml Pneumo Novum + 1 mg CpG 7909, IM

B

Pneumococcal vaccines

Group Type: PLACEBO_COMPARATOR

Pneumococcal vaccines

Intervention Type: BIOLOGICAL

Day 0: 1 ml Prevenar (double dose) + placebo, IM Day 90: 1 ml Prevenar (double dose) + placebo, IM Day 270: 0.5 ml Pneumo Novum + placebo, IM

Interventions

Pneumococcal vaccines + CPG 7909

Day 0: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 90: 1 ml Prevenar (double dose) + 1 mg CpG 7909, IM Day 270: 0.5 ml Pneumo Novum + 1 mg CpG 7909, IM

Intervention Type: BIOLOGICAL

Pneumococcal vaccines

Day 0: 1 ml Prevenar (double dose) + placebo, IM Day 90: 1 ml Prevenar (double dose) + placebo, IM Day 270: 0.5 ml Pneumo Novum + placebo, IM

Intervention Type: BIOLOGICAL

Other Intervention Names

Cpg 7909/Vaximmune(TM)

Eligibility Criteria

Inclusion Criteria

• Written informed consent and authority statement provided according to local regulatory and ethical practice using a participant information sheet and informed consent form approved by the responsible Ethics Committee.
• HIV-seropositive individuals.

Exclusion Criteria

• Pregnancy as determined by a positive urine beta-hCG (if female)
• Participant unwilling to use reliable contraception methods for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female)
• Currently breast-feeding (if female)
• Latest CD4 count < 200 x106 cells/µL
• Viral load (HIV RNA) > 50 copies/mL if on HAART (defined as at least three antiretrovirals including either a protease inhibitor or a NNRTI, i.e. combivir 300/150 mg x2 + stocrin 600 mg x1 for a minimum of 6 months)
• Previous enrollment in this study
• Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives (such as severe alcohol abuse, severe drug abuse, dementia)
• Unable to follow protocol regimen
• Pneumococcal vaccination 5 years or less prior to inclusion
• Planned participation in other vaccination trials during the time of the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Department of Infectious Diseases, Skejby

Principal Investigators

Ole Sogaard, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Infectious Diseases, Aarhus University Hospital, Denmark

Lars Ostergaard, MD,PhD,DmSC

Role: STUDY_DIRECTOR

Department of Infectious Diseases, Aarhus University Hospital, Denmark

Locations

Department of Infectious Diseases, Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

References

Offersen R, Melchjorsen J, Paludan SR, Ostergaard L, Tolstrup M, Sogaard OS. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults. Hum Vaccin Immunother. 2012 Aug;8(8):1042-7. doi: 10.4161/hv.20707. Epub 2012 Aug 1.

Reference Type: DERIVED

PMID: 22854665 (View on PubMed)

Sogaard OS, Lohse N, Harboe ZB, Offersen R, Bukh AR, Davis HL, Schonheyder HC, Ostergaard L. Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial. Clin Infect Dis. 2010 Jul 1;51(1):42-50. doi: 10.1086/653112.

Reference Type: DERIVED

PMID: 20504165 (View on PubMed)

Other Identifiers

2007-001588-31

Identifier Type: -

Identifier Source: org_study_id