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

NCT ID: NCT02443935

Last Updated: 2017-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2017-06-25

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.

Conditions

HIV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MGN1703

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

Group Type: EXPERIMENTAL

MGN1703

Intervention Type: DRUG

60 mg s.c. twice weekly for 4 weeks

MGN1703

Intervention Type: DRUG

60 mg s.c. twice weekly for 24 weeks

Interventions

MGN1703

60 mg s.c. twice weekly for 4 weeks

Intervention Type: DRUG

MGN1703

60 mg s.c. twice weekly for 24 weeks

Intervention Type: DRUG

Other Intervention Names

TLR9 agonist; CpG oligodeoxynucleotides; TLR9 agonist; CpG oligodeoxynucleotides

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars J Østergaard, MD,PhD,DMSc

Role: STUDY_CHAIR

Department for Infectious Diseases, Aarhus University Hospital, Denmark

Locations

Department for Infectious Diseases, Aarhus University Hospital

Aarhus N, , Denmark

Department for Infectious Diseases, Amager and Hvidovre Hospitals

Hvidovre, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 30932955 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28329286 (View on PubMed)

Other Identifiers

TEA-001

Identifier Type: -

Identifier Source: org_study_id