E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
human immunodeficiency viruses (HIV) |
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E.1.1.1 | Medical condition in easily understood language |
human immunodeficiency viruses (HIV) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 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.
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 18 years - Ability and willingness to provide written informed consent - Ability to attend the complete schedule of assessments and patient visits - Ability and willingness to have blood samples collected and stored indefinitely and used for various research purposes - HIV RNA < 50 copies/mL for at least 3 months on a 2nd generation integrase inhibitor (INSTI) based regimen - Females of childbearing potential should be on effective contraception
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E.4 | Principal exclusion criteria |
- Current presence of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification) - 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) - 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 - Pregnancy or breastfeeding - Patients unable to understand the study protocol or any other condition that in the investigator’s opinion may compromise compliance with the study protocol - 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) - Psychiatric and psychological disorders, which in the opinion of the investigator, will interfere with the trial conduct or safety of the participant - Previous participation in a trial evaluating an immune modulating agent - Active drug or alcohol use/addiction such that, in the opinion of the site investigator, would interfere with adherence to study requirements - Treatment failure on an integrase inhibitor containing regimen and reported baseline resistance - Creatinine Clearance <50 - Tuberculosis treatment - Documented M184V - Previous virological failure >200 copies/mL on NRTI - Subjects with history or presence of allergy to any of the study drugs or their components - ALT ≥5 times the ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin) |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points: - Quantification of viral markers as total HIV DNA, and RNA transcripts - Full length sequencing of the virus - Quantification of human pro-inflammatory mediators and markers of microbial translocation - Phenotype of innate immune cells - Function of immune cells - Metabolic parameters - Analysis of cardio-vascular risk in all or a subgroup of individuals.
Tertiary end point: Patient satisfaction. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint of evaluation of secondary end points: W240
Timepoint of evaluation of tertiary end point: W24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |