Clinical trial NCT03493568: Switch From Dual Regimens Based on Dolutegravir Plus a Reverse Transcriptase Inhibitor to E/C/F/TAF in Virologically Suppressed, HIV-1 Infected Patients (Be-OnE)
Official title: Open Label, Randomized (1:1) Clinical Trial to Evaluate Switching From Dual Regimens Based on Dolutegravir Plus a Reverse Transcriptase Inhibitor to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed, HIV-1 Infected Patients (Be-OnE Study).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV-1-infection
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2018-04-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatments

1. Genvoya 150Mg-150Mg-200Mg-10Mg Tablet ( 1 pill every 24 hours)
2. Dolutegravir 50 mg (1 pill every 24 hours) plus one Reverse Trascriptase Inhibitor (at label dose)
Primary purpose: TREATMENT

Brief summary: Research hypothesis:

Switching from dual regimens based on dolutegravir plus a RTI to a single tablet regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), lowers the exposure to Residual Viremia (and hence the risk of viral rebound), without increasing treatment toxicity.

Detailed description: Study design Randomized, single-center, open-label, 96-week superiority study. Patients with HIV-RNA \<50 copies/mL while receiving DTG plus one RTI will be randomized 1:1 to continue the ongoing treatment or to switch to E/C/F/TAF.

Randomization list will be a computer-generated list (with equal block sizes) and will be incorporated within an electronic clinical report form (eCRF).

Patients will be evaluated at screening, baseline, week 4, 8, 16, 24, 32, 40, 48, 60, 72, 84, 96 or premature discontinuation.

At each visit the following evaluations will be performed:

1. clinical assessment.
2. routine laboratory tests (hematological tests and clinical chemistry). Additional blood samples will be collected at specified visits for storage and further determinations (e.g. RV by a single-copy assay).

During follow-up, at different timepoints, patients will additionally undergo HIV-DNA quantification in PBMCs (BL, 48 and 96 weeks) and quality of life (QOL) and adherence assessement (BL, 48 and 96 weeks).

Viral load will be assessed by Abbott Real time PCR (Abbott RealTime HIV-1) Residual viremia (RV) will be defined as any detectable HIV-RNA value below 50 copies/mL Virologic failure will be defined as a confirmed rebound in plasma HIV-RNA levels ≥ 50 copies/mL

Subjects who meet a protocol-defined virologic failure during follow-up will be discontinued from the study.

At virologic failure subjects will perform genotypic HIV resistance testing and a determination in plasma of elvitegravir or DTG Cthrough.

HIV-DNA will be extracted from 1x106 peripheral blood mononuclear cells (PBMCs) by using Qiagen DNA extraction kit and quantified by Real Time PCR (ABI Prism 7900).

Eligibility criteria: Inclusion Criteria:

1. Age \>18 years
2. Willing and able to provide informed consent
3. On a stable (at least 3 months) antiretroviral therapy with DTG 50 mg QD plus one RTI
4. HIV-RNA \<50 copies/mL since at least 6 months

Exclusion Criteria:

1. Active AIDS-defining condition (except Kaposi's sarcoma non requiring systemic chemotherapy)
2. Serious illness requiring systemic treatment and/or hospitalization
3. Current use of immunomodulant or immunosuppressive drugs
4. Need (or will likely need) of treatment with antacids
5. Use of drugs contraindicated with study drugs, according to technical sheets
6. Previous suboptimal therapies with NRTIs or presence of TAMs (type 1 or 2) in previous resistance tests (patients with the 184I/V mutation alone are allowed to enter the study)
7. Resistance or previous virological failure to InSTIs
8. Detectable HCV-RNA
9. Documented allergy to COBI or EVG or FTC or tenofovir.
10. Absolute neutrophil count (ANC) \<500/µL
11. Haemoglobin \<8.0 g/dL
12. Platelet count \<50,000/µL
13. eGFR \<30 mL/min/1.73m2 by CKD-EPI equation
14. Alanine aminotransferase (ALT) more than 5 times the upper limit of normal (ULN)
15. Presence of Child Pugh Class B or C liver cirrhosis.
16. Pregnancy or breastfeeding
17. Woman of childbearing potential who does not agree to adopt highly effective contraception.

Primary outcomes:
measure: Residual Viremia
timeFrame: 48 weeks
Secondary outcomes:
measure: virological rebound
timeFrame: 48 weeks
measure: viral reservoir
timeFrame: 48 weeks
measure: QOL
timeFrame: 48 weeks
measure: Adherence
timeFrame: 48 weeks
measure: Virological failure
timeFrame: 96 weeks
measure: viral reservoir
timeFrame: 96 weeks
measure: QOL
timeFrame: 96 weeks
measure: Adherence.
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Milan
country: Italy
facility: Ospedale San Raffaele Scientific Institute
Study officials:
affiliation: Ospedale San Raffaele
name: Adriano Lazzarin, Prof
role: PRINCIPAL_INVESTIGATOR
References:
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