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

Primary Purpose

HIV

Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
MGN1703
MGN1703
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department for Infectious Diseases, Aarhus University Hospital
  • Department for Infectious Diseases, Amager and Hvidovre Hospitals

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MGN1703

Arm Description

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

Outcomes

Primary Outcome Measures

Part A: NK cell activation
As measured by CD69 expression
Part B: Quantification of the size of the HIV reservoir
As measured by quantitative viral outgrowth (qVOA) and total HIV DNA

Secondary Outcome Measures

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).
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
HIV DNA and others measures
Viral transcription
Plasma HIV RNA and cell-associated unspliced HIV RNA

Full Information

First Posted
April 30, 2015
Last Updated
June 28, 2017
Sponsor
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT02443935
Brief Title
Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection
Acronym
TEACH
Official Title
Toll-like Receptor 9 Enhancement of Antiviral Immunity in Chronic HIV-1 Infection: a Phase 1b/2a Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
June 1, 2017 (Actual)
Study Completion Date
June 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MGN1703
Arm Type
Experimental
Arm Description
TLR-9 agonist MGN1703 administered to HIV-1 positive patients on cART
Intervention Type
Drug
Intervention Name(s)
MGN1703
Other Intervention Name(s)
TLR9 agonist, CpG oligodeoxynucleotides
Intervention Description
60 mg s.c. twice weekly for 4 weeks
Intervention Type
Drug
Intervention Name(s)
MGN1703
Other Intervention Name(s)
TLR9 agonist, CpG oligodeoxynucleotides
Intervention Description
60 mg s.c. twice weekly for 24 weeks
Primary Outcome Measure Information:
Title
Part A: NK cell activation
Description
As measured by CD69 expression
Time Frame
12 weeks
Title
Part B: Quantification of the size of the HIV reservoir
Description
As measured by quantitative viral outgrowth (qVOA) and total HIV DNA
Time Frame
32 weeks
Secondary Outcome Measure Information:
Title
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).
Description
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).
Time Frame
12 weeks
Title
The size of the HIV-1 reservoir
Description
HIV DNA and others measures
Time Frame
12 weeks
Title
Viral transcription
Description
Plasma HIV RNA and cell-associated unspliced HIV RNA
Time Frame
12 weeks
Other Pre-specified Outcome Measures:
Title
Effects of MGN1703 on T and NK cell activation in the gut
Description
Changes in the expression of activation markers such as CD69.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars J Østergaard, MD,PhD,DMSc
Organizational Affiliation
Department for Infectious Diseases, Aarhus University Hospital, Denmark
Official's Role
Study Chair
Facility Information:
Facility Name
Department for Infectious Diseases, Aarhus University Hospital
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Facility Name
Department for Infectious Diseases, Amager and Hvidovre Hospitals
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
30932955
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.
Results Reference
derived
PubMed Identifier
28329286
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.
Results Reference
derived

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

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