POMALIDOMIDE for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Documented HIV-1 infection\n- Receiving combination ART for at least 1 years and being on the same ART regimen for at least 4 weeks at the screening visit\n- HIV-1 plasma RNA <50 copies/mL for >1 year (documented on at least 2 occasions within the 1 years and <20 copies/mL at screening. Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was <50 copies/mL\n- CD4+ T cell count >500 cells/L at screening and at least two CD4+ T cell counts >350 cells/L in the 24 months prior to screening\n- Ability and willingness to provide informed consent and to continue ART throughout the study phase I and to discontinue ART at the commencement of study phase II.\n- All participants must agree to avoid conception and undergo a strict set of criteria to avoid female participants becoming pregnant and male participants impregnating others."}

Exclusion criteria

• {"criterion_text":"- Known allergy or hypersensitivity to pomalidomide or its analogues\n- Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug\n- Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy as specified in the inclusion criteria\n- Prior or current lenalidomide, thalidomide or pomalidomide treatment or any condition where those treatments are indicated.\n- Unable or unwilling to adhere to protocol procedures\n- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures\n- Hepatic impairment defined as ALT >3 x upper limit of normal or Child-Pugh class C\n- Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min\n- Significant cardiac dysfunction\n- History of procoagulant disorders or venous/arterial thromboembolism\n- Receiving long-acting ART regimen with cabotegravir plus rilpivirine\n- Regular NSAID usage (>7 days continuous use in the last month) and/or unable to avoid regular NSAID use on the trial.\n- Laboratory values at screening: hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN), eGFR <50 mL/min, platelet count ≤100 x10^9/L, absolute neutrophil count ≤1.5x10^9/L, haemoglobin <10,0 g/dL, total lymphocyte count <800 cells/μL, CD4+ T cell count <500 cells/μL\n- Currently receiving anticoagulant therapy\n- Currently receiving other systemic immune-enhancing or immunosuppressive therapy (immunisation and locally applied agents are allowed) or having received any of those within 28 days prior to study entry\n- Received peg- IFNα treatment within 12 months\n- History of malignancy or transplantation, excluding adequately treated basal cell carcinoma\n- Co-infection with Hepatitis B, hepatitis C or D (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)\n- Current (within the previous two weeks) use of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine) at enrolment.\n- Any evidence of an active AIDS-defining opportunistic infection"}

Primary endpoints

• {"endpoint_text":"- Primary safety endpoint: defined as treatment-emerging adverse events (AEs) ≥ grade 3 probably or definitely related to study treatment.","definition_or_measurement_approach":"Treatment-emerging adverse events graded (severity) and assessed for relationship to study treatment; primary safety endpoint counts events ≥ grade 3 that are probably or definitely related to study treatment."}
• {"endpoint_text":"- Primary efficacy endpoint: Time from ART cessation until meeting ART restart criteria defined as the day on which plasma HIV-1 RNA levels have been sustained ≥ 1,000 copies/mL for 4 consecutive weeks, the day of confirmed plasma HIV RNA levels > 100.000 copies/mL or the day of confirmed CD4+ T cell count <350 cells/uL or confirmed CD4+ T cell percentage <15%).","definition_or_measurement_approach":"Time-to-event measure from ART cessation until predefined ART restart criteria are met (sustained plasma HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks; confirmed plasma HIV RNA >100,000 copies/mL; confirmed CD4+ T cell count <350 cells/µL; or confirmed CD4% <15%). Viral load measured by routine clinical plasma HIV-1 RNA assays; CD4 measured by standard clinical laboratory methods."}

Secondary endpoints

• {"endpoint_text":"- Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or possibly, probably or definitely related to study treatment.","definition_or_measurement_approach":"All treatment-emergent adverse events captured and graded by severity and relationship to study treatment."}
• {"endpoint_text":"- Rebound viral kinetics during the analytical treatment interruption including time to time to >50 copies/mL and >1,000 copies/mL as well as doubling times (with plasma HIV-1 RNA measured using routine care clinical assays).","definition_or_measurement_approach":"Plasma HIV-1 RNA measured using routine clinical assays; time to >50 and >1,000 copies/mL and viral doubling times calculated."}
• {"endpoint_text":"- Proportion maintaining VL <1,000 copies/mL HIV-1 RNA at the end of ATI","definition_or_measurement_approach":"Proportion of participants with plasma HIV-1 RNA <1,000 copies/mL at end of analytical treatment interruption measured by routine assays."}
• {"endpoint_text":"- Proportion of participants that have not met ART restart criteria at the end of ATI","definition_or_measurement_approach":"Proportion not meeting the predefined ART restart criteria at end of ATI (criteria as defined for primary efficacy endpoint)."}
• {"endpoint_text":"- HIV-specific CD4+ and CD8+ T cell responses by performing HIV peptide stimulation and intracellular cytokine staining (ICS) for HIV-specific T cells using flow cytometry","definition_or_measurement_approach":"HIV peptide stimulation followed by intracellular cytokine staining (ICS) and flow cytometry to quantify HIV-specific CD4+ and CD8+ T cell responses."}
• {"endpoint_text":"- The frequency of peripheral blood CD4+ T cells containing total and intact HIV-DNA while on suppressive ART","definition_or_measurement_approach":"Quantification of total and intact HIV-DNA in peripheral blood CD4+ T cells while on suppressive ART using molecular assays."}
• {"endpoint_text":"- The proportion of cells containing constitutive and inducible cell-associated multiply spliced HIV RNA (MS HIV-RNA) using the tat/rev induced limiting dilution assay (TILDA) while on suppressive ART","definition_or_measurement_approach":"TILDA (tat/rev induced limiting dilution assay) to measure constitutive and inducible multiply spliced HIV RNA in cells while on suppressive ART."}
• {"endpoint_text":"- The level of cell-associated unspliced HIV RNA (CA-US HIV RNA) in peripheral blood CD4+ T cells using real-time PCR while on suppressive ART","definition_or_measurement_approach":"Real-time PCR quantification of cell-associated unspliced HIV RNA in peripheral blood CD4+ T cells."}
• {"endpoint_text":"- Numbers and proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets","definition_or_measurement_approach":"Immunophenotyping (flow cytometry) to determine numbers and proportions of B cells, total lymphocytes, CD8+ and CD4+ T cells including memory subsets."}

Methods

• Flyers (DK and ES) — printed recruitment flyers listed in recruitment materials for Denmark and Spain targeting people living with HIV.
• Letters (DK) — recruitment invitation letters for potential participants in Denmark.
• Public websites (DK and ES) — recruitment material intended for public websites in Denmark and Spain.
• Social media (DK and ES) — recruitment material for social media channels in Denmark and Spain.
• Patient organisation outreach (ES) — involvement of a patient organisation site (Fundacion Fls De Lucha Contra El Sida...) for recruitment in Spain.
• Patient card and other subject information materials (DK) — materials for participants in Denmark including patient card and ART pausing information.

Denmark

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

19-02-2025

Processing Time Days

196

Number Of Sites

1

Number Of Participants

16

Spain

Earliest CTIS Part Ii Submission Date

04-03-2026

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

23

Number Of Sites

1

Number Of Participants

16

Primary sponsor

Full Name

Region Midtjylland

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"Sponsor duties codes: 1, 8","organisation_type":"Educational Institution"}