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

• ClinicalTrials.gov Identifier: NCT02443935
• Recruitment Status: Completed
• First Posted: May 14, 2015
• Last Update Posted: June 29, 2017
• Sponsor: University of Aarhus
• Information provided by (Responsible Party): University of Aarhus

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: MGN1703	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: April 2015
• Actual Primary Completion Date: June 1, 2017
• Actual Study Completion Date: June 25, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: MGN1703; TLR-9 agonist MGN1703 administered to HIV-1 positive patients on cART	Drug: MGN1703; 60 mg s.c. twice weekly for 4 weeks; Other Names: TLR9 agonist; CpG oligodeoxynucleotides; Drug: MGN1703; 60 mg s.c. twice weekly for 24 weeks; Other Names: TLR9 agonist; CpG oligodeoxynucleotides

Outcome Measures

Primary Outcome Measures :

1. Part A: NK cell activation [ Time Frame: 12 weeks ]
   As measured by CD69 expression
2. 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

Secondary Outcome Measures :

1. 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).
2. The size of the HIV-1 reservoir [ Time Frame: 12 weeks ]
   HIV DNA and others measures
3. Viral transcription [ Time Frame: 12 weeks ]
   Plasma HIV RNA and cell-associated unspliced HIV RNA

Other Outcome Measures:

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

Department for Infectious Diseases, Aarhus University Hospital

Aarhus N, Denmark, 8200

Department for Infectious Diseases, Amager and Hvidovre Hospitals

Hvidovre, Denmark, 2650

Sponsors and Collaborators

University of Aarhus

Investigators

• Study Chair: Lars J Østergaard, MD,PhD,DMSc; Department for Infectious Diseases, Aarhus University Hospital, Denmark

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT02443935
• Other Study ID Numbers: TEA-001
• First Posted: May 14, 2015
• Last Update Posted: June 29, 2017
• Last Verified: April 2015

Additional relevant MeSH terms:

Infections; CPG-oligonucleotide; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs