Pluto

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2026-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2026-525211-14-00

ClinicalTrials.gov

NCT07384624

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Therapy, Pharmacokinetic, Efficacy

Primary objectives phase I: To assess the efficacy of 1-day dual LRA combinations treatment on HIV reservoir reactivation in PLWH.
Primary objectives phase II: Efficacy of a 4-week dual LRA combination treatment on HIV reservoir reduction.

Secondary objectives 14

1. Key secondary objective phase I and II: To assess clinical safety and tolerability of the LRA drug combinations.
2. Phase I: To evaluate participant preference on drug combinations, trial experience, quality of life (QoL) and perceived stigma
3. Phase I: To measure plasma HIV-RNA kinetics during interventional treatment.
4. Phase I: To assess immunological functionality and phenotype.
5. Phase I: To analyze pharmacokinetics and pharmacodynamics of the combined investigational compounds.
6. Phase I: To analyze pharmacokinetics and pharmacodynamics of the combined investigational compounds.
7. Phase I: To evaluate correlation of in vivo and ex vivo reservoir reactivation.
8. Phase II: To evaluate participant trial experience, QoL and perceived stigma
9. Phase II: To assess the LRA effects on reservoir reactivation by prior LRA regimen exposure.
10. Phase II: To measure plasma HIV-RNA kinetics during interventional treatment.
11. Phase II: To assess Immunological functionality and phenotype.
12. Phase II: To analyze pharmacokinetics and pharmacodynamics of the combined investigational compounds.
13. Phase II: To assess drug-drug interactions between investigational drugs and ART
14. Phase II: To evaluate correlation of in vivo and ex vivo reservoir reactivation.

Conditions and MedDRA coding

HIV-1

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Documented HIV-1 infection, confirmed by Western Blot or PCR. 2. Age ≥ 18 years old. 2. Confirmed HIV1 subtype A, B, C or D. In case no HIV sequencing is available, proviral sequencing can be performed (preferably on left-over blood samples) to assess subtype. People with other HIV1 subtypes can only be included after discussion with Sponsor and is contingent on possible primary endpoint assay adaptation. 3. Uninterrupted ART therapy for a minimum 6 months. 4. Plasma HIV RNA ≤50 copies/ml prior to inclusion at two consecutive measurements at least three months apart. 5. No disclosed missed ART on more than 2 days per month. 6. Current blood CD4+T-cell count of ≥200 cells/mm3 7. No clinical signs of cellular immunodeficiency or AIDS. 8. Pre-ART plasma HIV RNA ≥1000 copies/mL. 9. Able to understand provided information and to give informed consent.

Exclusion criteria 1

1. A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Prior exposure to any of the studied LRAs in the previous 90 days 33 of 69 Based on CCMO protocol template CTR Version 3.0, May 2023 2026-525211-14-00, 1.3 (30-01-2026) CONFIDENTIAL 2. HIV-2 (double)infection 3. Co-infection with hepatitis B, unless resolved HBV (anti-HBc positive, anti-HBs positive and HBsAg negative) OR HBsAg positive and on continuous HBV-active antiviral therapy for ≥24 weeks prior to dosing, and HBV DNA undetectable or ≤ 200 IU/mL on two measurements (screening and within 4 weeks prior to enrolment), and no history of advanced fibrosis/cirrhosis (stage F2 and higher) 4. Co-infection with hepatitis C, measured by the presence of hepatitis C virus RNA in blood. 5. Co-medication with clinically significant interactions with LRA. 6. mRNA vaccine or adjuvant vaccine (e.g. Shingrix) in the previous 4 weeks. 7. Megaloblastic anaemia due to folate deficiency and untreated haemolysis of any cause 8. Active malignancy during the past year with the exception of basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi’s sarcoma treated with ART alone or other indolent malignancies. 9. History of suicide attempt or suicidal ideation. 10. History of ophthalmological medical problems leading to glaucoma or visual field disturbances (e.g. macula oedema). Refraction abnormalities that can be corrected by lenses are acceptable. 11. History of any medical condition with a causal relationship with hyperammonaemia. 12. History of epileptic seizures in the previous year. 13. Registered allergies for any of the investigational medical products 14. Sexually active participants who do not fit any of the following: a) Female subject of childbearing potential willing to comply with pregnancy tests before start and four weeks after end of treatment and willing to use of double contraceptive measures during and until 1 week after administration of study medication. Non-childbearing is defined by one of the following criteria: amenorrhoea for ≥ 1 year, premature ovarian failure, assigned male at birth, or having undergone bilateral salpingo-oophorectomy, or hysterectomy. b) Sexually active male PLWH who have sex with female partners of childbearing potential and willing to abstain from sex or willing to use condom protection during and until 1 week after administration of study medication. c) Sexually active male PLWH who have sex with postmenopausal female partners and willing to abstain from sex or willing to use condom protection or with a postmenopausal female partner on pre-exposure prophylaxis during and until 1 week after administration of study medication. d) Male PLWH who have sex with male partners and willing to abstain from sex or willing to use a condom protection during and until 1 week after administration of study medication. e) Male PLWH who have sex with male partners on preexposure prophylaxis during and until 1 week after administration of study medication. 15. Any lab abnormalities at screening as listed below: a) Moderate kidney impairment, defined as eGFR <50 mL/min. In PLWH on dolutegravir- or bictegravir-based ART regimens, cystatin C-based eGFR can be used, since possible drug interference with tubular creatinine excretion which leads to eGFR underestimation. b) Moderate hepatic impairment, defined as bilirubin > 3 x upper limit of normal (ULN) or ALT > 3x ULN c) Inadequate blood counts, defined as: haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females), Absolute neutrophil count <1000 cells/mm3, thrombocytes <100 x109/L, international standardized ratio >1.6, activated partial thromboplastin time >40 seconds

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase I : Fold change in cell-associated HIV-RNA at time points 6 (T=6) and 24 hours (T=24) after LRA treatment compared to baseline (T=0) before treatment. Phase II: Log transformed HIV-DNA at T=4 weeks compared to T=0.

Secondary endpoints 14

1. Key secondary endpoint Phase I and phase II: The number and severity of clinical and biochemical adverse events using CTCAEv6.0.
2. Phase I: Quantitative and qualitative patient reported outcomes of treatment satisfaction, QoL and stigma by validated questionnaires at T=0, T=24hr and T=7 days and by a semi-structured interview before the intervention and at T=24hr.
3. Phase I: Change in plasma HIV-RNA between and within arms at T=6hr, T=24hr and T = 7 days compared to T=0.
4. Phase I: The change of the frequency, functionality and phenotype of immune cell subpopulations; total T cells and HIV specific CD4+ and CD8+ T cells, B-cell differentiation, HIV specific B-cell clonotype and immunoglobulin sequence, and HIV specific antibody function, between and within the groups at T=7 days, compared to T=0.
5. Phase I: Drug plasma levels of LRA compounds at T=0h, T= 6hr, T=24hr and T=7 days.
6. Phase I: Drug plasma levels of ART at T=0hr, T=6hr, T=24hr and T=7 days.
7. Phase I: The correlation between ex vivo and in vivo fold change in cell-associated HIV-RNA from T=0 to T=24hr.
8. Phase II: Quantitative and qualitative patient reported outcomes of treatment satisfaction, QoL and stigma by questionnaires and by a semi-structured interview at T=0 to T=4 weeks.
9. Phase II: Fold change cell associated HIV RNA from T=0 to T=24hr in participants in phase 2 com-pared to T=0 to T=24hr in participants in phase 1 overall and by prior LRA exposure.
10. Phase II: Change in plasma HIV-RNA absolute copies/mL and proportion with viral target detectable, >30, >50, and >200 c/mL within group at T=24hr, T=1, 2, 3, and 4 weeks compared to T=0.
11. Phase II: The change of the frequency, functionality and phenotype of immune cell subpopulations; total T cells and HIV specific CD4+ and CD8+ T cells, B-cell differentiation, HIV specific B-cell clonotype and immunoglobulin sequence, and HIV specific antibody function, at T=1 and T=4 weeks compared to T=0.
12. Phase II: Drug plasma levels of LRA compounds at T=1, 2, 3, and 4 weeks.
13. Phase II: Drug plasma of ART levels T=1, 2, 3, and 4 weeks.
14. Phase II: The correlation between ex vivo and in vivo fold change in cell-associated HIV-RNA from T=0 to T=24hr overall and by prior LRA exposure.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Casper Rokx

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Casper Rokx

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 13 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