HIV MedDRA version: 19.0 Level: LLT Classification code 10073675 Term: HIV infection CDC category unspecified System Organ Class: 100000004862
Conditions
Interventions
Product Name: MGN1703
Pharmaceutical Form: Solution for injection
INN or Proposed INN: dSLIM
Other descriptive name: MGN1703
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Sponsors
Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To perform a detailed characterization of the numeric, phenotypic, and functional properties of circulating HIV-1-specific T cells and NK cells during MGN1703 treatment;Secondary Objective: • To evaluate the safety and tolerability of MGN1703 administration in HIV infected patients • To evaluate the effect of MGN1703 on circulating monocytes and pDC cell activation, quantity, and phenotype (activated vs. resting) • To evaluate the effect of MGN 1703 on HIV-1 transcriptional activity in circulating CD4+ cells and on low level viremia • To evaluate the effect of MGN1703 on the size of the HIV-1 reservoir • To characterize the immunological effects of MGN1703 in the gut • To determine the effect of MGN1703 on the quantity of HIV-1 RNA/DNA in the gut • To investigate the impact of MGN1703 on the levels of soluble inflammatory markers in plasma;Primary end point(s): Part A: Changes in proportions of activated NK cells Part B: Change in HIV-1 DNA in circulating total CD4+ T cells. ;Timepoint(s) of evaluation of this end point: Part A: Visits 1, 1b, 2, 4, 5, 6, 8, 10, 11, 11b, 12, 13, 14, 15 Part B: Visits 16, 20 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PART A • Safety evaluation, as measured by adverse events (AE), adverse reactions (AR), serious adverse events (SAE), serious adverse reactions (SAR), suspected unexpected serious adverse reactions (SUSAR), and dose-limiting toxicity (Visits 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 11b, 12, 13, 14, 15) • Absolute T, NK, and NKT cell counts and phenotypic properties will be characterized using standard cell marker panels (Visits 1, 1b, 2, 4, 5, 6, 8, 10, 11, 11b, 12, 13, 14, 15) • Functional properties of cytotoxic T cells, NK, and NKT cells will be investigated by analysing cytokine secretion properties (Visits 2, 4, 12, 14) • Change in the capacity of CD8 T cells and NK cells to mediate inhibition of viral replication ex vivo (Visits 2, 4, 12, 14) • Change in ADCC (Visits 1, 3, 11, 15) • Gene expression changes and global genomic change in methylation pattern of integrated HIV (Visits 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 15) • Dynamics of HIV-1 DNA, episomal HIV-1 DNA (2-LTR), and nonspliced HIV-1 RNA in circulating total CD4+ T cell (Visits 1, 2, 3, 4, 11, 12, 13, 14, 15) • Change from baseline in numeric and phenotypic characteristics of monocytes (e.g. CD169 expression), pDCs, and B cells (Visits 2, 4, 12, 14) • Plasma HIV-RNA, as measured by the single copy assay and NAT (Visits 1, 2, 3, 4, 11, 13, 14, 15) • Change from baseline in HIV-1 DNA, episomal HIV-1 DNA (2-LTR), and unspliced HIV-1 RNA in rectal gut mucosa (Visits 1b, 11b) • Change from baseline in immune cell activation and function in rectal gut mucosa as measured by flow cytometry (Visits 1b, 11b) • Plasma cytokines (e.g. IL-6, IL-8, IP-10) and immune activation biomarker levels (Visits 1, 1b, 2, 3, 4, 5, 6, 8, 10, 11, 11b, 12, 13, 14, 15) • Genetic, virological, and immunological predictors of treatment response (Visits 1, 1b, 2, 3, 4, 5, 6, 8, 10, 11, 11b, 12, 13, 14, 15) • If virus is induced compare sequence of blood vs. gut virus to see if the stimulated virus is | — |
Countries
Denmark
Contacts
Public ContactOle Schmeltz Søgaard
Aarhus University Hospital
Outcome results
None listed