Clinical trial NCT06660498: Pomalidomide As an Immune-enhancing Agent for the Control of HIV
Official title: Pomalidomide As an Immune-enhancing Agent for the Control of HIV (PEACH): an Investigator-initiated Phase I/IIb Clinical Trial in People Living with HIV on ART and During Analytical Treatment Interruption
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: HIV-1 Infection
Keywords: Immune-enhancing therapy
HIV
ART
Analytical treatment interruption
Investigator-initiated
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2024-10-28
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 1:1 to pomalidomide 2 mg/d or matching placebo concurrent with aspirin 75 mg.
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the safety and efficacy of pomalidomide in HIV-1-infected individuals on ART and to determine the impact of pomalidomide on virological control in people living with HIV during an analytical treatment interruption.


Eligibility criteria: Documented HIV-1 infection

* Age 18-70 years, both included.
* Receiving combination ART for at least 1 year and being on the same ART regimen for at least 4 weeks at the screening visit
* HIV-1 plasma RNA \<50 copies/mL for \>1 year (documented on at least 2 occasions within the last year 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
* CD4+ T cell count \>500 cells/uL at screening and at least two CD4+ T cell counts \>350 cells/uL in the 24 months prior to screening
* 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.
* 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.
* A female participant, may be eligible to enter and participate in the study if she:

  * Is of non-child-bearing potential defined as either:

    * Age ≥ 50 years and naturally amenorrheic for ≥ 1 year (amenorrhoea following cancer therapy or during breast-feeding does not rule out childbearing potential)
    * Premature ovarian failure confirmed by a specialist gynecologist
    * Previous bilateral salpingo-oophorectomy, or hysterectomy
    * XY genotype, Turner syndrome, uterine agenesis
  * Is of child-bearing potential with a negative pregnancy test at both Screening and Day 0 and agrees to use one of the following methods of contraception to avoid pregnancy:

    * Complete abstinence from penile-vaginal intercourse from 4 weeks prior to administration of investigational medical product (IMP), 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.

A heterosexually active male participant, may be eligible to enter and participate in the study if he is:

* Willing to complete abstinence from penile-vaginal intercourse from 4 weeks prior to administration of IP, throughout the study, and for at least 4 weeks after discontinuation of all study medications
* willing to use an effective method of contraception (condom) including those who have had vasectomy performed
* 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.

Primary outcomes:
measure: Efficacy of treatment, measured as the time from ART cessation until meeting ART restart criteria.
timeFrame: From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: Safety of treatment, measured by the number of treatment-emergent adverse events (AEs) of grade 3 or higher that are probably or definitely related to the study treatment.
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
Secondary outcomes:
measure: Safety, defined as all other treatment-emerging adverse events (AEs)
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: Rebound viral kinetics during the ATI, including plasma HIV-1 RNA copies/mL doubling times
timeFrame: From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: The proportion of participants maintaining HIV-1 RNA levels below 1,000 copies/mL at the end of the ATI.
timeFrame: From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: The proportion of participants who have not met ART restart criteria at the end of the ATI.
timeFrame: From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: The frequency of peripheral blood CD4+ T cells containing total and intact HIV-DNA while on suppressive ART
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: HIV-specific CD4+ responses
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: HIV-specific CD8+ T cell responses
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: The proportion of cells containing constitutive and inducible MS HIV-RNA
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: The level of CA-US HIV RNA in peripheral blood CD4+ T cells
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: Numbers of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
measure: Proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets
timeFrame: From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: University of Aarhus
name: Thomas A. Rasmussen, Associate professor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: