Clinical trial NCT02443935: Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection
Official title: Toll-like Receptor 9 Enhancement of Antiviral Immunity in Chronic HIV-1 Infection: a Phase 1b/2a Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2015-05-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Documented HIV-1 infection
* Age \>18 years
* CD4+ T-cell count \>350/µL at screening
* On cART (for a minimum of 12 months)
* Able to give informed consent.

Exclusion Criteria:

* Pregnancy as determined by a positive urine beta-hCG (if female)
* Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the entire study period.
* Currently breast-feeding (if female)
* Viral load (HIV RNA) \> 50 copies/mL
* Contraindication to receive MGN1703 as per current investigator brochure
* Presence of acute bacterial infection or undiagnosed febrile condition
* Concurrent chronic systemic immune therapy or immunosuppressant medication, including continuous systemic steroid treatment within the last 2 weeks prior to randomization
* Use of antibiotic therapy within the last 2 weeks prior to randomization
* Known HBV or HCV infection
* 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

Primary outcomes:
measure: Part A: NK cell activation
timeFrame: 12 weeks
measure: Part B: Quantification of the size of the HIV reservoir
timeFrame: 32 weeks
Secondary outcomes:
measure: 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).
timeFrame: 12 weeks
measure: The size of the HIV-1 reservoir
timeFrame: 12 weeks
measure: Viral transcription
timeFrame: 12 weeks
Other outcomes:
measure: Effects of MGN1703 on T and NK cell activation in the gut
timeFrame: 12 weeks
Locations:
city: Aarhus N
country: Denmark
facility: Department for Infectious Diseases, Aarhus University Hospital
city: Hvidovre
country: Denmark
facility: Department for Infectious Diseases, Amager and Hvidovre Hospitals
Study officials:
affiliation: Department for Infectious Diseases, Aarhus University Hospital, Denmark
name: Lars J Østergaard, MD,PhD,DMSc
role: STUDY_CHAIR
References:
citation: Vibholm LK, Konrad CV, Schleimann MH, Frattari G, Winckelmann A, Klastrup V, Jensen NM, Jensen SS, Schmidt M, Wittig B, Zuwala K, Mack K, Olesen R, Hua S, Lichterfeld M, Ostergaard L, Denton PW, Tolstrup M, Sogaard OS. Effects of 24-week Toll-like receptor 9 agonist treatment in HIV type 1+ individuals. AIDS. 2019 Jul 1;33(8):1315-1325. doi: 10.1097/QAD.0000000000002213.
citation: Vibholm L, Schleimann MH, Hojen JF, Benfield T, Offersen R, Rasmussen K, Olesen R, Dige A, Agnholt J, Grau J, Buzon M, Wittig B, Lichterfeld M, Petersen AM, Deng X, Abdel-Mohsen M, Pillai SK, Rutsaert S, Trypsteen W, De Spiegelaere W, Vandekerchove L, Ostergaard L, Rasmussen TA, Denton PW, Tolstrup M, Sogaard OS. Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. Clin Infect Dis. 2017 Jun 15;64(12):1686-1695. doi: 10.1093/cid/cix201.