Venetoclax for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- Documented HIV-1 infection\n- Age 18-70 years (both included) at screening\n- CD4+ T cell count >300/µL at screening\n- ART naïve at screening\n- Able to give informed consent\n- Ability and willingness to provide informed consent and to continue ART throughout the study\n- A female, may be eligible to enter and participate in the study if she: -\tIs of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, - Is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: \tComplete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications \tAny intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year \tMale partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject \tApproved hormonal contraception (Where other medications to be used in the study (e.g., efavirenz and darunavir) are known, or are likely, to significantly interact with systemic contraceptives, resulting in decreased efficacy of the contraceptive, then alternative methods of non-hormonal contraception are recommended) \tAny other method with published data showing that the expected failure rate is <1% per year \tAny contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of study therapy.\n- All participants must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization, egg donation) during the study\n- Heterosexually active male if they are - willing to use an effective method of contraception (anatomical sterility in self that is confirmed prior to study entry) or - agree on the use of an effective method of contraception with an effective failure rate of < 1% by his partner (hormonal contraception, intra-uterine device (IUD), or anatomical sterility) from the day prior to the first dose and for at least 4 weeks after discontinuation of study drug.\n- All participants must agree to use condoms during all sexual intercourse in situations where HIV transmission may still occur, i.e. until fully suppressed on ART (plasma HIV-1 RNA <50 copies/mL)"}

Exclusion criteria

• {"criterion_text":"- Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy\n- Evidence of or strong suspicion that HIV infection was acquired during active PrEP use\n- The following laboratory values at screening (lab tests may be repeated, as clinically indicated, to obtain acceptable values before failure at screening is concluded but supportive therapies are not to be administered within the week prior to screening tests): - Platelet count ≤100 x109/L - Absolute neutrophil count ≤1.0x109/L - Haemoglobin <10,0 g/dL - CD4+ T cell count <300 cells/uL\n- Any concomitant disease where venetoclax treatment is indicated\n- Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)\n- Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)\n- Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)\n- Current use of P-gp substrates with narrow therapeutic index (such as such as digoxin, tacrolimus, cyclosporine, sirolimus, dabigatran, colchicine, loperamide)\n- Current use of strong or moderate CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin, St. John’s wort, bosentan, efavirenz and etravirine); intermittent use of moderate CYP3A4 inducers such as modafinil and nafcillin may be used but should be avoided as much as possible\n- Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry\n- Known hypersensitivity to the components of venetoclax or its analogues\n- Any evidence of an active AIDS-defining opportunistic infection\n- Individuals who intend to modify their ART regimen within the study period\n- Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug\n- Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures\n- Unable or unwilling to adhere to protocol procedures\n- History of malignancy or transplantation, excluding adequately treated basal cell carcinoma\n- Co-infection with hepatitis B defined as HBsAg-positive or Hepatitis C defined as HCV-RNA positive (Individuals with prior hepatitis B or C infection that is now cleared are eligible for enrolment); For individuals with isolated anti-HBcAb (cleared hepatitis B), the chosen ART regimen must include TDF or TAF\n- Impaired liver function with AST or ALT >3 times upper limit of normal\n- Severe hepatic impairment (Class C) as determined by Child-Pugh classification\n- Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min\n- Significant cardiac dysfunction\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"}

Primary endpoints

• {"endpoint_text":"- Primary safety endpoint: Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365)","definition_or_measurement_approach":"Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365) (as stated)."}
• {"endpoint_text":"- Primary effect endpoint: The frequency of peripheral blood CD4+ T cells containing intact HIV-DNA at day 365 using the Cross-Subtype Intact Proviral DNA Assay (IPDA)","definition_or_measurement_approach":"Frequency measured at day 365 using the Cross-Subtype Intact Proviral DNA Assay (IPDA) on peripheral blood CD4+ T cells."}

Secondary endpoints

• {"endpoint_text":"- Safety defined as all other treatment-emerging AEs, graded according to severity and assessed as either not related or related to study treatment (from Day 0 to Day 365)","definition_or_measurement_approach":"All treatment-emerging AEs graded by severity and attribution, from Day 0 to Day 365."}
• {"endpoint_text":"- Decay rates of plasma HIV RNA following initiation of ART","definition_or_measurement_approach":"Measurement of plasma HIV RNA over time after ART initiation to calculate decay rates (method not further specified)."}
• {"endpoint_text":"- Levels of CD4+ T cells expressing intracellular p24 quantified by flow cytometry","definition_or_measurement_approach":"Intracellular p24 in CD4+ T cells quantified by flow cytometry."}
• {"endpoint_text":"- The frequency of peripheral blood CD4+ T cells containing total HIV-DNA using real-time or digital droplet PCR","definition_or_measurement_approach":"Measurement of total HIV-DNA in peripheral blood CD4+ T cells using real-time PCR or digital droplet PCR."}
• {"endpoint_text":"- The proportion of cells containing constitutive and inducible cell-associated multiply spliced HIV RNA (MS HIV-RNA) at day 365 using the tat/rev induced limiting dilution assay (TILDA)","definition_or_measurement_approach":"Proportion measured at day 365 using the tat/rev induced limiting dilution assay (TILDA)."}
• {"endpoint_text":"- The level of cell-associated unspliced HIV RNA (CA-US HIV RNA) in peripheral blood CD4+ T cells using real-time or digital droplet PCR","definition_or_measurement_approach":"CA-US HIV RNA levels in peripheral blood CD4+ T cells measured by real-time PCR or digital droplet PCR."}
• {"endpoint_text":"- Changes in numbers and proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets (from Day 0 to Day 365)","definition_or_measurement_approach":"Immunophenotyping to quantify changes in lymphocyte subsets from Day 0 to Day 365 (method implied: flow cytometry)."}
• {"endpoint_text":"- The ratio of intact and total HIV-DNA in peripheral blood CD4+ T cells (from Day 0 to Day 365)","definition_or_measurement_approach":"Ratio derived from measurements of intact (IPDA) and total HIV-DNA (real-time or ddPCR) in peripheral blood CD4+ T cells from Day 0 to Day 365."}

Methods

• Public websites (Denmark) - document: K2_Recruitment material_Public websites_DK
• Poster (Denmark) - document: K2_Recruitment material_Poster_DK
• Recruitment arrangements (Denmark) - document: K1_Recruitment arrangements (associatedEntityId 263779)
• Public websites (Spain) - document: K2_Recruitment material_Public websites_ES
• Social media (Spain) - document: K2_Recruitment material_Social media_ES
• Poster (Spain) - document: K2_Recruitment material_Poster_ES
• Recruitment arrangements (Spain) - document: K1_Recruitment arrangements_2025-521841-26-00_v2 (associatedEntityId 260355)

Denmark

Earliest CTIS Part Ii Submission Date

04-12-2025

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

39

Number Of Sites

6

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

24-11-2025

Latest Decision Or Authorization Date

02-01-2026

Processing Time Days

39

Number Of Sites

4

Number Of Participants

26

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":"Codes: 1, 8","organisation_type":"Educational Institution"}