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

HIV Infections Clinical Trial

— ITAP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00562939
• Other study ID #: 2007-001588-31
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 23, 2007
• Last updated: January 20, 2009
• Start date: January 2008
• Est. completion date: January 2009

Study information

• Verified date: January 2009
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Danish National Committee on Biomedical Research EthicsDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• 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
• 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

Locations

Country	Name	City	State
Denmark	Department of Infectious Diseases, Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of vaccine high responders - defined as 2-fold increase and IgG levels =1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group		At day 270	No
Secondary	Functional activity of anticapsular antibodies measured by OPA		At day 90, 120, 270, 300	No
Secondary	Safety/Tolerability		During the entire trial period	Yes
Secondary	Nasopharyngeal pneumococcal colonization		At day 270	No
Secondary	Predictors of antibody response, i.e. CD4+ cell count and sCD163		At baseline	No
Secondary	Numbers of vaccine high responders - defined as 2-fold increase and IgG levels =1 µg/mL to at least 5 of 7 pneumococcal serotypes (by quantitative IgG measurements) - in the CpG 7909 group vs. the control group		At day 90,120 and 300	No
Secondary	Quantity and differentiation of IgG subtypes for HAART-experienced and HAART-naive individuals		Day 0, 90, 120	No
Secondary	Cytokine response to various antigens by in vitro cell stimulation for HAART-experienced and HAART-naive individuals		At day 0, 90, 120	No