Interventional, multicenter, open-label, randomized, non-comparative trial evaluating the safety, in terms of HBV virological control, of 2 antiviral treatment relief strategies, in patients co-infected with the HIV-1 and HBV viruses

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Inserm

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Immune System Diseases [C20], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

14 May 2025 → ongoing

Decision date (initial)

2024-03-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ANRS Maladies Infectieuses Emergentes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The main objective of this trial is to evaluate at 96 weeks the safety with respect to chronic viral hepatitis B control of 2 treatment reduction strategies for patients with previously controlled HIV-HBV co-infection on continuous triple therapy

Secondary objectives 7

1. HBV virological response at 48 weeks
2. HIV virological response at 48 and 96 weeks
3. Selection of HBV resistance mutations at the time of virological failure
4. Predictive factors for virological rebound(s)
5. Clinical and biological tolerance
6. Participants' quality of life
7. HBV virological response at 96 weeks between arms

Conditions and MedDRA coding

co-infected with the HIV-1 and HBV viruses

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. HIV-1-HBV co-infection (positive HIV-1 serology associated with 2 positive HBsAg serologies within more than 6 months)
2. ALT < 3N at pre-inclusion
3. For women of childbearing potential, negative pregnancy test and commitment to use effective contraception throughout the trial
4. Person affiliated with or benefiting from a social security system
5. Free, informed, written consent, signed by the person and the investigator at the latest on the day of inclusion and before any examination carried out as part of the study (article L1122-1-1 of the Public Health Code)
6. Age ≥ 18 years
7. Fibroscan less than 6 months < 9kPa
8. Current daily antiretroviral tritherapy not modified for ≥ 12 months must including tenofovir disoproxil fumarate (TDF) 245mg or tenofovir alafenamide fumarate (TAF -25mg) associated to lamivudine (3TC – 300mg) or emtricitabine (FTC - 200mg) and a NNRTI or PI/r or INSTI to choose from o NNRTI = efavirenz, rilpivirine, etravirine, doravirine o PI/r = atazanavir/r ou darunavir/r o INSTI = bictegravir, dolutegravir, elvitegravir/cobicistat, raltegravir
9. Absence of documented HBV and HIV genotypic resistance compromising virologic control of any of the maintenance strategies. Patients with no genotypic history may be included)
10. HIV CV < 50cp/ml for ≥ 2 years (only 1 annual blip allowed if HIV CV < 200cp/ml and previous and subsequent viral loads are undetectable)
11. HBV CV < 10 IU/ml for ≥ 2 years (only 1 annual blip allowed if HBV CV < 200IU/ml and if previous and subsequent viral loads are undetectable)
12. Have ≥ 3 available measurements of HIV CV < 50cp/ml and HBV CV < 10 IU/mL over the past 30 months (including that of pre-inclusion
13. CD4 lymphocytes > 250/mm3 at pre-inclusion
14. Positive Ag HBs HBV serology at pre-inclusion

Exclusion criteria 12

1. HIV-2 infection
2. HIV and/or HBV genotype not compatible with dual therapy DTG-3TC or DRVr-3TC
3. HBeAg+.
4. Fibrosis history at stage F3-F4 in pre-therapy evaluated by PBH, fibrotest and/or fibroscan with a value of Elastometry ≥ 9kPa
5. Chronic active viral hepatitis C (HCV RNA positive)
6. Delta co-infection
7. Alcohol consumption > 14 units/week for women and 21 units/week for men
8. Current treatment with chemo- or immunotherapy (including interferon or interleukins)
9. Active opportunistic infection or acute treatment for opportunistic infection
10. Any condition (drug use, neurological, neuropsychiatric, etc.) that, in the judgment of the investigator, may compromise patient compliance and adherence to the protocol
11. Pregnant or breastfeeding woman or refusal of contraception
12. Major incapacity, legal protection, guardianship or curatorship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint was the proportion of participants with HBV virological failure at 96 weeks. Failure was defined as two successive HBV viral load measurements >10 IU/mL or one HBV viral load measurement above the detection threshold followed by permanent discontinuation of the strategy or follow-up in the trial.

Secondary endpoints 11

1. • HBV virological success rate at 48 weeks
2. • HIV virological success rate at 48 and 96 weeks
3. • Time to virological failure (rebound HBV and/or HIV viral load)
4. • The rate of participants with at least one HBV viral load blip until S48 and until S96
5. • Selection of HBV resistance mutations at the time of virological failure
6. • Incidence of grade 3 or higher adverse events of grade 3 or higher, incidence of adverse events and incidence of strategy discontinuation of the strategy at W48 and W96
7. • Evolution of CD4 and CD8 T lymphocytes, and the CD4/CD8 ratio from W0 to W48 and W96
8. • Evolution of metabolic parameters (total cholesterol, LDL-c, HDL-c, triglycerides and fasting blood sugar) from W0 to W48 and W96
9. • Participants' compliance with treatment (self-questionnaire) at S0, S12, S24, S48, S72 and S96
10. • Participants' quality of life using the Pro-Qol self-questionnaire at S0, S12, S24, S48, S72 and S96
11. HBV virological success rate at 96 weeks between arms

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Inserm

Sponsor organisation

Inserm

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Inserm

Contact name

fatoumata Coulibaly

Public contact point

Organisation

Inserm

Contact name

fatoumata Coulibaly

Locations

1 EU/EEA country · 21 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 15 files

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

Application history

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