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HIV-1-infectionPhase 3Be-OnENCT03493568

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)

A Phase 3 study testing Genvoya 150Mg-150Mg-200Mg-10Mg Tablet and Dolutegravir 50 mg plus one RTI in people with HIV-1-infection, run by IRCCS San Raffaele at 2 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
HIV-1-infection
What is being tested?
Genvoya 150Mg-150Mg-200Mg-10Mg Tablet and Dolutegravir 50 mg plus one RTI
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
2 sitesItaly
Study dates
6 Feb 2017to 31 Jul 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Active AIDS-defining condition (except Kaposi's sarcoma non requiring systemic chemotherapy)
  • Serious illness requiring systemic treatment and/or hospitalization
  • Current use of immunomodulant or immunosuppressive drugs
  • Need (or will likely need) of treatment with antacids
  • Use of drugs contraindicated with study drugs, according to technical sheets
  • 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)
Show all 17Show fewer
  • Resistance or previous virological failure to InSTIs
  • Detectable HCV-RNA
  • Documented allergy to COBI or EVG or FTC or tenofovir.
  • Absolute neutrophil count (ANC) <500/µL
  • Haemoglobin <8.0 g/dL
  • Platelet count <50,000/µL
  • eGFR <30 mL/min/1.73m2 by CKD-EPI equation
  • Alanine aminotransferase (ALT) more than 5 times the upper limit of normal (ULN)
  • Presence of Child Pugh Class B or C liver cirrhosis.
  • Pregnancy or breastfeeding
  • Woman of childbearing potential who does not agree to adopt highly effective contraception.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Ospedale San Raffaele

    Milan, Lombardy, 20127

  • Ospedale San Raffaele Scientific Institute

    Milan, 20127

Other trials in Italy

About this study

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).

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.

Read the 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).

Conditions
HIV-1-infection
Being tested
Genvoya 150Mg-150Mg-200Mg-10Mg Tablet, Dolutegravir 50 mg plus one RTI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Genvoya 150Mg-150Mg-200Mg-10Mg TabletDrug

    switch to Genvoya 150Mg-150Mg-200Mg-10Mg Tablet in patients virologically suppressed HIV-1 infected patients.

  • Dolutegravir 50 mg plus one RTIDrug

    Continuing Dolutegravir 50 mg (1 pill every 24 hours) plus one RTI (at label dose)

Study groups in NCT03493568
Study groupRoleWhat they receive
Genvoya 150Mg-150Mg-200Mg-10Mg TableExperimentalswitch to the treatment Genvoya 150Mg-150Mg-200Mg-10Mg Table (1 pill every 24 hour)
Receives: Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet
Dolutegravir 50 mg plus one RTI (at label dose)Active comparatorContinuing Dolutegravir 50 mg (1 pill every 24 hours) plus one RTI (at label dose)
Receives: Drug: Dolutegravir 50 mg plus one RTI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Residual Viremia

    To investigate RV through 48 weeks in virologically suppressed patients randomized to continue treatment with DTG plus a single RTI or to switch to E/C/F/TAF.

    Measured: 48 weeks

Secondary outcomes (8)

  1. virological rebound

    To investigate the occurrence of virological rebound above 50 HIV-RNA copies/mL;

    Measured: 48 weeks

  2. viral reservoir

    To investigate changes in viral reservoir (HIV-DNA)

    Measured: 48 weeks

  3. QOL

    To investigate changes in the quality of life (administration of questionnaire ISSQoL uses five- point Likert scales 1 never 2 rarely 3 sometimes 4 often 5 always)

    Measured: 48 weeks

  4. Adherence

    To investigate changes in adherence (administration of questionnaire uses scale ranges from 0 to 100)

    Measured: 48 weeks

  5. Virological failure

    proportion of patient in virological rebound

    Measured: 96 weeks

  6. viral reservoir

    change in viral reservoir (HIV-DNA extracted from peripheral blood mononuclear cells by using Qiagen DNA extraction kit and quantified by Real Time PCR)

    Measured: 96 weeks

  7. QOL

    To investigate changes in the quality of life (administration of questionnaire To investigate changes in the quality of life (administration of questionnaire ISSQoL uses five- point Likert scales 1 never 2 rarely 3 sometimes 4 often 5 always))

    Measured: 96 weeks

  8. Adherence.

    To investigate changes in adherence (administration of questionnaire uses scale ranges from 0 to 100 )

    Measured: 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2018
  2. Study start6 Feb 2017
  3. Primary completion20 Mar 2018
  4. Study completion31 Jul 2020

Why it stopped: The futility analysis on 24-week results estimated that there was only 2% probability of verifying the study hypothesis of a higher proportion pat. with no residual viremia through 48w in arm E/C/F/TAF

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03493568
Sponsor's protocol ID
Be-OnE Study
Acronym
Be-OnE
Status last verified
Feb 2024
First submitted
27 Mar 2018
Last updated
9 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data shared in Scientific Congress (abstract and pubblications)

Publications

  • Margolis DA, Brinson CC, Smith GHR, de Vente J, Hagins DP, Eron JJ, Griffith SK, Clair MHS, Stevens MC, Williams PE, Ford SL, Stancil BS, Bomar MM, Hudson KJ, Smith KY, Spreen WR; LAI116482 Study Team. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015 Oct;15(10):1145-1155. doi: 10.1016/S1473-3099(15)00152-8. Epub 2015 Jul 19.

    PubMed 26201299

  • Riddler SA, Aga E, Bosch RJ, Bastow B, Bedison M, Vagratian D, Vaida F, Eron JJ, Gandhi RT, Mellors JW; ACTG A5276s Protocol Team. Continued Slow Decay of the Residual Plasma Viremia Level in HIV-1-Infected Adults Receiving Long-term Antiretroviral Therapy. J Infect Dis. 2016 Feb 15;213(4):556-60. doi: 10.1093/infdis/jiv433. Epub 2015 Sep 2.

    PubMed 26333941

  • Gianotti N, Canducci F, Galli L, Cossarini F, Salpietro S, Poli A, Nozza S, Spagnuolo V, Clementi M, Sampaolo M, Ceresola ER, Racca S, Lazzarin A, Castagna A. HIV DNA loads, plasma residual viraemia and risk of virological rebound in heavily treated, virologically suppressed HIV-infected patients. Clin Microbiol Infect. 2015 Jan;21(1):103.e7-103.e10. doi: 10.1016/j.cmi.2014.08.004. Epub 2014 Oct 13.

    PubMed 25636935

  • Gianotti N, Galli L, Salpietro S, Cernuschi M, Bossolasco S, Maillard M, Spagnuolo V, Canducci F, Clementi M, Lazzarin A, Castagna A. Virological rebound in human immunodeficiency virus-infected patients with or without residual viraemia: results from an extended follow-up. Clin Microbiol Infect. 2013 Dec;19(12):E542-4. doi: 10.1111/1469-0691.12266. Epub 2013 Jul 24.

    PubMed 23890370

  • Maggiolo F, Callegaro A, Cologni G, Bernardini C, Velenti D, Gregis G, Quinzan G, Soavi L, Iannotti N, Malfatto E, Leone S. Ultrasensitive assessment of residual low-level HIV viremia in HAART-treated patients and risk of virological failure. J Acquir Immune Defic Syndr. 2012 Aug 15;60(5):473-82. doi: 10.1097/QAI.0b013e3182567a57.

    PubMed 22481602

  • Doyle T, Smith C, Vitiello P, Cambiano V, Johnson M, Owen A, Phillips AN, Geretti AM. Plasma HIV-1 RNA detection below 50 copies/ml and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis. 2012 Mar 1;54(5):724-32. doi: 10.1093/cid/cir936. Epub 2012 Jan 11.

    PubMed 22238167

  • Mills A, Arribas JR, Andrade-Villanueva J, DiPerri G, Van Lunzen J, Koenig E, Elion R, Cavassini M, Madruga JV, Brunetta J, Shamblaw D, DeJesus E, Orkin C, Wohl DA, Brar I, Stephens JL, Girard PM, Huhn G, Plummer A, Liu YP, Cheng AK, McCallister S; GS-US-292-0109 team. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis. 2016 Jan;16(1):43-52. doi: 10.1016/S1473-3099(15)00348-5. Epub 2015 Nov 2.

    PubMed 26538525

  • Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003 Oct;41(10):4531-6. doi: 10.1128/JCM.41.10.4531-4536.2003.

    PubMed 14532178

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Genvoya 150Mg-150Mg-200Mg-10Mg Tablet and Dolutegravir 50 mg plus one RTI in people with HIV-1-infection, run by IRCCS San Raffaele at 2 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The futility analysis on 24-week results estimated that there was only 2% probability of verifying the study hypothesis of a higher proportion pat. with no residual viremia through 48w in arm E/C/F/TAF). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Residual Viremia (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03493568, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2024.

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