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)

NCT03493568 | Terminated Phase 3 DMC

• 1 other identifier: Be-OnE Study
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (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.

  48 weeks

Secondary Outcomes (8)

• virological rebound

  48 weeks

• viral reservoir

  48 weeks

• QOL

  48 weeks

• Adherence

  48 weeks

• Virological failure

  96 weeks

Study Arms (2)

Genvoya 150Mg-150Mg-200Mg-10Mg Table

EXPERIMENTAL

switch to the treatment Genvoya 150Mg-150Mg-200Mg-10Mg Table (1 pill every 24 hour)

Drug: Genvoya 150Mg-150Mg-200Mg-10Mg Tablet

Dolutegravir 50 mg plus one RTI (at label dose)

ACTIVE COMPARATOR

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

Drug: Dolutegravir 50 mg plus one RTI

Interventions

Genvoya 150Mg-150Mg-200Mg-10Mg Tablet DRUG

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

Genvoya 150Mg-150Mg-200Mg-10Mg Table

Dolutegravir 50 mg plus one RTI DRUG

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

Dolutegravir 50 mg plus one RTI (at label dose)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Gilead Sciences: collaborator

Study Sites (2)

Ospedale San Raffaele

Milan, Lombardy, 20127, Italy

Location

Ospedale San Raffaele Scientific Institute

Milan, 20127, Italy

Location

Related Publications (8)

• 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.

  PMID: 26201299 BACKGROUND

• 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.

  PMID: 26333941 BACKGROUND

• 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.

  PMID: 25636935 BACKGROUND

• 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.

  PMID: 23890370 BACKGROUND

• 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.

  PMID: 22481602 BACKGROUND

• 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.

  PMID: 22238167 BACKGROUND

• 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.

  PMID: 26538525 BACKGROUND

• 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.

  PMID: 14532178 BACKGROUND

MeSH Terms

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; dolutegravir

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Adriano Lazzarin, Prof

  Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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)

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 10, 2018
• Study Start: February 6, 2017
• Primary Completion: March 20, 2018
• Study Completion: July 31, 2020
• Last Updated: February 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

IT (2)