Virological and immunological assessment in HIV positive participants on 2DR versus 3DR in a prospective randomized controlled switch trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Gent

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

26 May 2020 → 12 Mar 2026

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515265-34-00

EudraCT number

2020-000685-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective is to demonstrate non inferiority at W48 of the 2DR DTG/3TC (Dovato) regimen compared to BIC/TAF/FTC (Biktarvy) in HIV-1 infected individuals in terms of the amount of intact replication-competent HIV-1 sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by an intact proviral DNA assay, present in blood CD4 cells.

Secondary objectives 5

1. Quantification of immune activation markers in both arms, will be explored and should not differ more than 20%.
2. To assess impact of the DTG/3TC vs BIC/FTC/TAF on metabolic health; evolutions of these outcomes will be compared among the DTG/3TC vs BIC/FTC/TAF group.
3. To assess the impact of switching through a patient questionnaire.
4. To demonstrate non inferiority at W144 and W240 of the 2DR DTG/3TC vs BIC/TAF/FTC in terms of the amount of intact replicationcompetent HIV-1 sequences with a non-inferiority margin of 12% quantified by the fraction intact HIV viral sequences quantified by an intact proviral DNA assay, present in blood CD4 cells.
5. In all participants or in a subgroup indientified as high and very high C-V risk group will be proposed a duplex carotis at W240 to assess the intima media tickness as a surrogate marker for generalised atherosclerosis and risk of cardio-vascular disease.

Conditions and MedDRA coding

human immunodeficiency viruses (HIV)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. Ability and willingness to provide written informed consent
3. Ability to attend the complete schedule of assessments and patient visits
4. Ability and willingness to have blood samples collected and stored indefinitely and used for various research purposes
5. HIV RNA < 50 copies/mL for at least 3 months on a 2nd generation integrase inhibitor (INSTI) based regimen
6. Females of childbearing potential should be on effective contraception

Exclusion criteria 16

1. Current presence of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification).
2. Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (seroconversion= HBV antigen or viral load negative and positive HBV surface antibody).
3. Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry.
4. Pregnancy or breastfeeding.
5. Patients unable to understand the study protocol or any other condition that in the investigator’s opinion may compromise compliance with the study protocol.
6. Decompensated liver cirrhosis (Child-Pugh B/C) Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
7. Psychiatric and psychological disorders, which in the opinion of the investigator, will interfere with the trial conduct or safety of the participant.
8. Previous participation in a trial evaluating an immune modulating agent.
9. Active drug or alcohol use/addiction such that, in the opinion of the site investigator, would interfere with adherence to study requirements.
10. Treatment failure on an integrase inhibitor containing regimen and reported baseline resistance.
11. Creatinine Clearance <50.
12. Tuberculosis treatment.
13. Documented M184V.
14. Previous virological failure >200 copies/mL on NRTI.
15. Subjects with history or presence of allergy to any of the study drugs or their components.
16. ALT >5 times the ULN, OR ALT >3xULN and bilirubin >1.5xULN (with >35% direct bilirubin).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the amount of intact replication competent HIV sequences at W48 quantified by the fraction intact HIV viral sequences quantified by an intact proviral DNA assay, present in blood CD4 cells.

Secondary endpoints 7

1. Quantification of viral markers as total and intact HIV DNA, and RNA transcripts at baseline, W48, W144 and W240.
2. Full length sequencing of the virus at baseline, W144 and W240.
3. Quantification of human pro-inflammatory mediators and markers of microbial translocation at baseline, W48, W144 and W240.
4. Phenotype of innate immune cells at baseline W48, W144, W240.
5. Function of immune cells at baseline,W144 and W240.
6. Metabolic parameters at baseline, W24, W48, W72, W96, W120,W144, W186, W192, W216 and W240.
7. Analysis of cardio-vascular risk at W240 based on risk stratification at D0, W48 and W144 in all or a subgroup of individuals.

Investigational products

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

Test 4

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Gent

Sponsor organisation

Universitair Ziekenhuis Gent

Address

Corneel Heymanslaan 10

City

Gent

Postcode

9000

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Sophie Degroote

Public contact point

Organisation

Universitair Ziekenhuis Gent

Contact name

Sophie Degroote

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 20 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