HIV infection MedDRA version: 20.1 Level: LLT Classification code 10073675 Term: HIV infection CDC category unspecified System Organ Class: 100000004862
Conditions
Interventions
Product Name: MGN1703 (Lefitolimod)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: dSLIM
Other descriptive name: MGN1703
Concentration unit: mg/ml milligram(s)/millilitre
Concentrati
Sponsors
Department of infectious Diseases, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Documented HIV-1 infection - ?Adults age 18-65 year - On antiretroviral therapy for a minimum of 18 months - CD4+ count >500 at screening - HIV-1 RNA plasma level of 50 but =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Any significant acute medical illness requiring hospitalization in the past 4 weeks - Any evidence of an active AIDS-defining opportunistic infection - Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy - The following laboratory values at screening, the values can be repeated within the screening period, but test results must be available before baseline (Day 0) and checked for eligibility: o Hepatic transaminases (AST or ALT) =3 x upper limit of normal (ULN) o Serum total bilirubin =3 ULN o Estimated glomerular filtration rate (eGFR) =50 mL/min (based on serum creatinine) o Platelet count =100 x109/L o Absolute neutrophil count =1x109/L - Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen or hepatitis C virus RNA in blood - History of: o Malignancy, excluding non-melanoma skin cancers, or organ transplantation - Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry - Known resistance to >2 classes of ART - Known hypersensitivity to the components of lefitolimod, 3BNC117, 10-1074 or their analogues - Pre-existing autoimmune or antibody-mediated diseases - Women who are pregnant or breastfeeding, or with a positive pregnancy test as determined by a positive urine beta- human chorionic gonadotropin test during screening or women of child bearing potential who are unwilling or unable to use an acceptable method of non-estrogen containing contraception (according to the Danish Medicines Agency guidelines) to avoid pregnancy during the study - Males or females who are unwilling or unable to use barrier contraception during sexual intercourse until plasma HIV-1 RNA is undetectable using standard assays
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effects of a TLR9 agonist (Lefitolimod) and/or administration of potent bNAbs (3BNC117 and 10-1074) on time to viral rebound during analytical treatment interruption. ;Secondary Objective: - To evaluate the safety and tolerability of the Investigational Medicinal Products (IMP)s - To compare viral load (plasma HIV-1 RNA) kinetics (e.g. doubling time) between study arms - To evaluate the effect of the IMPs on the amount of HIV-1 DNA in CD4+ T cells - To evaluate the effect of the IMPs on the functional HIV-1 reservoir in CD4+ T cells - To compare HIV-specific immunity, T cell phenotype, immune activation and cytokine production between study arms;Primary end point(s): Time from the day of cART cessation to the day of the last of three consecutive plasma HIV-1 RNA measurements >10,000 copies/mL.;Timepoint(s) of evaluation of this end point: The following visits: 5-9 and 10a-10j | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety evaluation, as measured by Adverse Events (AE), Adverse Reactions (ARs), Serious Adverse Events (SAE), Serious Adverse Reactions (SAR) and CD4 cell change from baseline to end of study 2. ?Rebound virus kinetics including time to >50 copies/mL and >1,000 copies/mL as well as doubling time during the analytical treatment interruption as measured by plasma HIV-1 RNA (Cobas TaqMan; Lower limit of quantitation 20 copies/mL) 3. To compare time without ART between study arms;Timepoint(s) of evaluation of this end point: 1. All visits 2. During the analytical treatment interruption (visit 5-9 and 10a-10j) 3. During the analytical treatment interruption (visit 5-9 and 10a-10j) | — |
Countries
Australia, Denmark, Norway, United States
Contacts
Public ContactOle Schmeltz Søgaard
Department of Infectious Diseases, Aarhus University Hospital
Outcome results
None listed