Pomalidomide as an immune-enhancing agent for the control of HIV (PEACH)

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

13 Feb 2025 → ongoing

Decision date (initial)

2024-09-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To determine the impact of pomalidomide on virological control in people living with HIV (PLWH) during an analytical interruption of ART.

Secondary objectives 2

1. To determine the effect of pomalidomide on HIV persistence in PLWH on ART
2. To determine the effect of pomalidomide on HIV-specific CD8+ T cell responses and NK cell cytotoxicity in PLWH on ART

Conditions and MedDRA coding

HIV-1-infection

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Documented HIV-1 infection
2. Receiving combination ART for at least 1 years and being on the same ART regimen for at least 4 weeks at the screening visit
3. 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
4. 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
5. 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.
6. 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 20

1. Known allergy or hypersensitivity to pomalidomide or its analogues
2. Regular NSAID usage (>7 days continuous use in the last month) and/or unable to avoid regular NSAID use on the trial.
3. Currently receiving anticoagulant therapy
4. 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
5. Received peg- IFNα treatment within 12 months
6. History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
7. Co-infection with Hepatitis B, hepatitis C or D (Individuals with prior hepatitis C infection that is now cleared are eligible for enrolment)
8. Current (within the previous two weeks) use of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine) at enrolment.
9. Any evidence of an active AIDS-defining opportunistic infection
10. Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
11. 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
12. Prior or current lenalidomide, thalidomide or pomalidomide treatment or any condition where those treatments are indicated.
13. Unable or unwilling to adhere to protocol procedures
14. Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
15. Hepatic impairment defined as ALT >3 x upper limit of normal or Child-Pugh class C
16. Impaired renal function with estimated creatinine clearance (eGFR) <50 mL/min
17. Significant cardiac dysfunction
18. History of procoagulant disorders or venous/arterial thromboembolism
19. Receiving long-acting ART regimen with cabotegravir plus rilpivirine
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary safety endpoint: defined as treatment-emerging adverse events (AEs) ≥ grade 3 probably or definitely related to study treatment.
2. 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%).

Secondary endpoints 9

1. 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.
2. 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).
3. Proportion maintaining VL <1,000 copies/mL HIV-1 RNA at the end of ATI
4. Proportion of participants that have not met ART restart criteria at the end of ATI
5. 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
6. The frequency of peripheral blood CD4+ T cells containing total and intact HIV-DNA while on suppressive ART
7. 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
8. 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
9. Numbers and proportions of B cells, total lymphocytes, CD8+ T cells and CD4+ T cells including memory subsets

Investigational products

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

Test 1

Placebo 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 · 2 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 25 files

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

Application history

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