HIV-1 Infection
Conditions
Keywords
Immune-enhancing therapy, HIV, ART, Analytical treatment interruption, Investigator-initiated
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.
Interventions
DRUGPomalidomide 2 mg
Participants will receive pomalidomide 2 mg/d concurrently with aspirin 75 mg for three cycles, each consisting of 21 days on and a minimum of 7 days off.
DRUGPlacebo
Participants will receive placebo concurrently with aspirin 75 mg for three cycles, each consisting of 21 days on and a minimum of 7 days off.
DRUGAspirin 75 mg
Auxiliary Medicinal Product
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Participants will be randomized 1:1 to pomalidomide 2 mg/d or matching placebo concurrent with aspirin 75 mg.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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 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 * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy of treatment, measured as the time from ART cessation until meeting ART restart criteria. | From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria |
| 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. | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of participants maintaining HIV-1 RNA levels below 1,000 copies/mL at the end of the ATI. | From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| The proportion of participants who have not met ART restart criteria at the end of the ATI. | From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| The frequency of peripheral blood CD4+ T cells containing total and intact HIV-DNA while on suppressive ART | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| HIV-specific CD4+ responses | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| Safety, defined as all other treatment-emerging adverse events (AEs) | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | AEs are graded according to severity and assessed as either not related or possibly, probably or definitely related to study treatment. |
| The proportion of cells containing constitutive and inducible MS HIV-RNA | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| The level of CA-US HIV RNA in peripheral blood CD4+ T cells | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| Numbers of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| Proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| HIV-specific CD8+ T cell responses | From enrollment to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
| Rebound viral kinetics during the ATI, including plasma HIV-1 RNA copies/mL doubling times | From ATI to the end of treatment at visit 18 or 16 weeks after meeting ART restart criteria | — |
Countries
Australia, Denmark
Contacts
Primary ContactThomas A. Rasmussen, Associate professor, MD, PhD
Outcome results
None listed