Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection (TEACH)
Combination antiretroviral treatment (cART) effectively suppresses virus replication and partially restores immune functions. However, cART cannot cure HIV infection.
This study aim to investigate whether the antiviral immune response can be enhanced and/or viral transcription reactivated with MGN1703. MGN1703 is an agonist to toll-like receptor (TLR) 9. Activation of TLR9 has been shown to augment innate and adaptive immune effector functions, most notably enhanced NK cell and T cell functions.
Furthermore, TLR9 agonists have been shown in vitro to reactivate viral transcription in latently infected cells, potentially leading to enhanced recognition of infected cells by the immune effector cells.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Toll-like Receptor 9 Enhancement of Antiviral Immunity in Chronic HIV-1 Infection: a Phase 1b/2a Trial|
- Part A: NK cell activation [ Time Frame: 12 weeks ]As measured by CD69 expression
- Part B: Quantification of the size of the HIV reservoir [ Time Frame: 32 weeks ]As measured by quantitative viral outgrowth (qVOA) and total HIV DNA
- Safety and tolerability, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR). [ Time Frame: 12 weeks ]Safety evaluation, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR) and suspected unexpected serious adverse reactions (SUSAR).
- The size of the HIV-1 reservoir [ Time Frame: 12 weeks ]HIV DNA and others measures
- Viral transcription [ Time Frame: 12 weeks ]Plasma HIV RNA and cell-associated unspliced HIV RNA
- Effects of MGN1703 on T and NK cell activation in the gut [ Time Frame: 12 weeks ]Changes in the expression of activation markers such as CD69.
|Study Start Date:||April 2015|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
TLR-9 agonist MGN1703 administered to HIV-1 positive patients on cART
60 mg s.c. twice weekly for 4 weeks
Other Names:Drug: MGN1703
60 mg s.c. twice weekly for 24 weeks
In Part A, participants will receive 4 weeks MGN1703 therapy (60 mg s.c. twice weekly). During the 4 weeks, participants will be closely monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part A is 14-16 study subjects.
In Part B, participants will receive 24 weeks of MGN1703 therapy (60 mg s.c. twice weekly). During the 24 weeks, participants will be frequently monitored for safety and therapeutic effects of the drug. Targeted enrolment in Part B is 10-12 study subjects, preferentially recruited from part A.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02443935
|Department for Infectious Diseases, Aarhus University Hospital|
|Aarhus N, Denmark, 8200|
|Department for Infectious Diseases, Amager and Hvidovre Hospitals|
|Hvidovre, Denmark, 2650|
|Study Chair:||Lars J Østergaard, MD,PhD,DMSc||Department for Infectious Diseases, Aarhus University Hospital, Denmark|