Research into topiramate to remove the hidden HIV in people living with HIV taking HIV treatment

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]

Trial duration

7 Jul 2024 → ongoing

Decision date (initial)

2024-06-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511532-27-00

ClinicalTrials.gov

NCT06282783

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy

1. To assess the effect of topiramate on HIV reactivation in people living with HIV on antiretroviral therapy.
2. To evaluate the clinical safety and tolerability of topiramate.

Secondary objectives 1

1. 1. To evaluate the influence of sex on reactivation potential, and safety and tolerability of topiramate. 2. To assess the effect of topiramate on the size of the HIV reservoir. 3. To evaluate the relationship between HIV reactivation and pharmacokinetics. 4. To assess the correlation of ex vivo LRA responses on in vivo latency reversal.

Conditions and MedDRA coding

human immunodeficiency virus 1 (HIV-1)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Documented HIV-1, subtype B or C • Aged 18 or over • On ART for a minimum of 2 consecutive years • HIV-1 RNA plasma level <30 copies/mL for at least two consecutive measurements prior to inclusion (viral blips with a detectable HIVRNA 30-200 c/mL preceded and followed by HIV-RNA <30 are allowed) • CD4+ T cell count ≥200 cells/mm3 at screening • Able to understand the information and give informed consent

Exclusion criteria 1

1. • Any major acute medical condition requiring hospitalisation within the past 4 weeks. • Presence of an active opportunistic infection that defines acquired immunodeficiency syndrome (AIDS). • Any medical condition deemed by the investigator to hinder compliance with the study treatment. • The following laboratory values at the screening phase (available before baseline (T0)): o Hepatic transaminases (AST or ALT) ≥3 times the upper limit of normal. o Serum total bilirubin ≥3 times the ULN. o Estimated glomerular filtration rate (eGFR) ≤60 mL/min based on CKD-EPI. o Haemoglobin <6.5 mmol/L (males) or <6.0 mmol/L (females) o Leucocytes <2.5 x109/L o Absolute neutrophil count <1000 cells/mm3 o Thrombocytes <100 x109/L • Active malignancy during the past year except for basal carcinoma of the skin, stage 0 cervical carcinoma, Kaposi Sarcoma treated with ART alone, or other indolent malignancies. • Participants who are unwilling or unable to use barrier contraception during sexual intercourse during the study. • History of suicide or suicidal ideation. • 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. • History of any medical condition with a causal relationship with hyperammonemia. • Participants using phenytoin, carbamazepine, digoxin, lithium, or valproic acid throughout the trial period. • Any concurrent medicine use associated with hyperammonemia (e.g. valproic acid). • Participants with active substance abuse. • Participants who have registered allergies to the investigational medical product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. The fold change in cell-associated (CA) HIV-1 RNA after topiramate treatment (T2 (6h), T3 (24h)) compared to baseline (T0). 2. The frequency and severity of adverse events after topiramate treatment.

Secondary endpoints 1

1. 1. The change in CA HIV-1 RNA compared between arms. 2. Plasma concentrations of topiramate compared between arms. 3. The frequency and severity of adverse events compared between arms. 4. The change in reservoir size after topiramate treatment compared to baseline. 5. The plasma concentration of topiramate compared to CA HIV-1 RNA.

Investigational products

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

Test 1

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 · 1 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 7 files

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

Application history

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