Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection

NCT02443935 | Completed Phase 1

• 1 other identifier: TEA-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV

Outcome Measures

Primary Outcomes (2)

• Part A: NK cell activation

  As measured by CD69 expression

  12 weeks

• Part B: Quantification of the size of the HIV reservoir

  As measured by quantitative viral outgrowth (qVOA) and total HIV DNA

  32 weeks

Secondary Outcomes (3)

• 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).

  12 weeks

• The size of the HIV-1 reservoir

  12 weeks

• Viral transcription

  12 weeks

Other Outcomes (1)

• Effects of MGN1703 on T and NK cell activation in the gut

  12 weeks

Study Arms (1)

MGN1703

EXPERIMENTAL

TLR-9 agonist MGN1703 administered to HIV-1 positive patients on cART

Drug: MGN1703

Interventions

MGN1703 DRUG

60 mg s.c. twice weekly for 4 weeks

Also known as: TLR9 agonist, CpG oligodeoxynucleotides

MGN1703

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (2)

Department for Infectious Diseases, Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Department for Infectious Diseases, Amager and Hvidovre Hospitals

Hvidovre, 2650, Denmark

Location

Related Publications (2)

• 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.

  PMID: 30932955 DERIVED

• 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.

  PMID: 28329286 DERIVED

MeSH Terms

Interventions

MGN1703

Study Officials

• Lars J Østergaard, MD,PhD,DMSc

  Department for Infectious Diseases, Aarhus University Hospital, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: May 14, 2015
• Study Start: April 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 25, 2017
• Last Updated: June 29, 2017

Record last verified: 2015-04

Locations

DK (2)