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

HIV Clinical Trial

— TEACH  

Official title:

Toll-like Receptor 9 Enhancement of Antiviral Immunity in Chronic HIV-1 Infection: a Phase 1b/2a Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02443935
• Other study ID #: TEA-001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 30, 2015
• Last updated: June 28, 2017
• Start date: April 2015
• Est. completion date: June 25, 2017

Study information

• Verified date: April 2015
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 25, 2017
• Est. primary completion date: June 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• MGN1703
60 mg s.c. twice weekly for 4 weeks
• MGN1703
60 mg s.c. twice weekly for 24 weeks

Locations

Country	Name	City	State
Denmark	Department for Infectious Diseases, Aarhus University Hospital	Aarhus N
Denmark	Department for Infectious Diseases, Amager and Hvidovre Hospitals	Hvidovre

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effects of MGN1703 on T and NK cell activation in the gut	Changes in the expression of activation markers such as CD69.	12 weeks
Primary	Part A: NK cell activation	As measured by CD69 expression	12 weeks
Primary	Part B: Quantification of the size of the HIV reservoir	As measured by quantitative viral outgrowth (qVOA) and total HIV DNA	32 weeks
Secondary	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).	12 weeks
Secondary	The size of the HIV-1 reservoir	HIV DNA and others measures	12 weeks
Secondary	Viral transcription	Plasma HIV RNA and cell-associated unspliced HIV RNA	12 weeks