Inhibiting BCL-2 at the start of HIV treatment to reduce the HIV reservoir in people living with HIV

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Midtjylland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

20 Feb 2026 → ongoing

Decision date (initial)

2026-01-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To determine the safety of venetoclax administration in PLWH at the time of ART initiation

Secondary objectives 2

1. To determine the impact on viral decay and HIV persistence of venetoclax administration in PLWH at the time of ART initiation
2. To determine the impact of venetoclax administered at the time of ART initiation on cellular apoptosis pathways in PLWH

Conditions and MedDRA coding

HIV-1 infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Documented HIV-1 infection
2. Age 18-70 years (both included) at screening
3. CD4+ T cell count >300/µL at screening
4. ART naïve at screening
5. Able to give informed consent
6. Ability and willingness to provide informed consent and to continue ART throughout the study
7. A female, may be eligible to enter and participate in the study if she: - Is 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:  Complete 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  Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year  Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner for that subject  Approved 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)  Any other method with published data showing that the expected failure rate is <1% per year  Any contraception method must be used consistently, in accordance with the approved product label and for at least 4 weeks after discontinuation of study therapy.
8. 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
9. 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.
10. 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 24

1. Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
2. Evidence of or strong suspicion that HIV infection was acquired during active PrEP use
3. Any concomitant disease where venetoclax treatment is indicated
4. Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
5. Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)
6. Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)
7. Current use of P-gp substrates with narrow therapeutic index (such as such as digoxin, tacrolimus, cyclosporine, sirolimus, dabigatran, colchicine, loperamide)
8. 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
9. Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry
10. Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
11. Known hypersensitivity to the components of venetoclax or its analogues
12. Any evidence of an active AIDS-defining opportunistic infection
13. Individuals who intend to modify their ART regimen within the study period
14. Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
15. Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
16. Unable or unwilling to adhere to protocol procedures
17. History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
18. 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
19. Impaired liver function with AST or ALT >3 times upper limit of normal
20. Severe hepatic impairment (Class C) as determined by Child-Pugh classification
21. Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
22. Significant cardiac dysfunction
23. 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
24. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary safety endpoint: Safety defined as treatment-emerging adverse events (AEs) related to study treatment (from Day 0 to Day 365)
2. 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)

Secondary endpoints 8

1. 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)
2. Decay rates of plasma HIV RNA following initiation of ART
3. Levels of CD4+ T cells expressing intracellular p24 quantified by flow cytometry
4. The frequency of peripheral blood CD4+ T cells containing total HIV-DNA using real-time or digital droplet PCR
5. 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)
6. 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
7. 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)
8. The ratio of intact and total HIV-DNA in peripheral blood CD4+ T cells (from Day 0 to Day 365)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Midtjylland

Sponsor organisation

Region Midtjylland

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Region Midtjylland

Contact name

Thomas A. Rasmussen

Public contact point

Organisation

Region Midtjylland

Contact name

Thomas A. Rasmussen

Third parties 1

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications