Early DOlutegravir/LAmivudine Switching After Virological Suppression (EDOLAS Study)

NCT04979468 | Unknown Phase 3 DMC

• 1 other identifier: 2019-004241-32
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 25

Brief Summary

Phase III, randomized, open-label, multicentre, active-controlled, non-inferiority study evaluating the efficacy and safety of early switching to dolutegravir/lamivudine (DTG/3TC) in single-pill, in HIV-1 infected individuals currently taking an INSTI-based three-drug first-line regimen for less than 18 months and who have been virologically suppressed with HIV-1 RNA \<50 copies/mL

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Non-inferior efficacy of switching

  Proportion of participants with virological rebound (viral load ≥50 copies/mL or premature discontinuations, irrespective of reason, with last viral load ≥50 copies/mL) at week 48

  48 weeks

Secondary Outcomes (8)

• Efficacy of switching

  48 weeks

• Safety and tolerability

  100 weeks

• Immunologic response and dysfunction

  100 weeks

• Emergent drug resistance-associated mutations

  100 weeks

• RT and INSTI resistance-associated mutations

  100 weeks

Study Arms (2)

ARM A

OTHER

Participants in Arm A will be randomized to switch to DTG/3TC 50/300 mg QD until week 48 (early switch).

Drug: DOVATO

ARM B

OTHER

Participants in Arm B will continue the INSTI-based ART regimen until week 48, and then will be switched to DTG/3TC through week 96 (delayed switch).

Drug: DOVATO

Interventions

DOVATO DRUG

Dovato is a medicine for treating infection with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).

Also known as: dolutegravir/lamivudine

ARM A; ARM B

Eligibility Criteria

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

You may qualify if:

• HIV-1 documented infection;
• Aged 18 years or older at the time of signing the informed consent;
• Stable INSTI-based first-line three-drug ART (switch between different NRTIs are allowed; e.g. from TDF/FTC to TAF/FTC or ABC/3TC, from TAF/FTC to TDF/FTC or ABC/3TC, from ABC/3TC to TAF/FTC or TDF/FTC). Any change of INSTI will not be allowed. Only the following regimens will be allowed:
• RAL 1200 mg QD plus TDF/FTC or TAF/FTC;
• RAL 1200 mg QD plus ABC/3TC;
• EVG/COBI/FTC/TDF or EVG/COBI/FTC/TAF;
• DTG plus TDF/FTC or TAF/FTC;
• DTG/ABC/3TC or DTG plus ABC/3TC;
• BIC/TAF/FTC
• Previous INSTI-based first-line ART lasting less than 18 months before screening;
• To have reached a HIV-1 RNA \<50 copies/mL during INSTI first-line therapy for less than 12 months. At least a single HIV-1 RNA determination below the threshold within the 6 months before enrollment is required (if a following determination in present, this should not be ≥50 copies (cp)/mL)
• HIV-1 RNA below 50 copies/mL at the screening visit;
• No known allergy or intolerance to the study drugs or their components or drugs of their class;
• A female person is eligible to enter the study if it is confirmed that she is:
• Not pregnant confirmed by a negative serum pregnancy test at both Screening and Day1;

You may not qualify if:

• Having failed virologically;
• Having changed the INSTI drug;
• Any major INSTI- or NRTI-resistance-associated mutation documented before starting ART;
• Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study;
• Evidence of Hepatitis B virus (HBV) infection based on the results of testing at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-Hbc), hepatitis B surface antigen antibody (anti-HBs) and, possibly, HBV DNA as follows:
• Individuals positive for HBsAg are excluded;
• Individuals negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded;
• HCV-RNA positivity needing for any hepatitis C virus (HCV) therapy during the study;
• Ongoing malignancy other than cutaneous Kaposi's sarcoma (not requiring systemic therapy), basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia;
• Active opportunistic infections requiring active treatment;
• Creatinine clearance of \<50 mL/min/1.73m2 via CKD-EPI method;
• Individuals with severe hepatic impairment (Child Pugh class C) and/or unstable liver disease;
• Any verified Grade 4 laboratory abnormality at screening assessment;
• Alanine aminotransferase (ALT) \>5 times the upper limit of normal (ULN) or ALT \>3xULN and bilirubin \>1.5xULN (with \>35% direct bilirubin) at screening assessment;
• Receipt of investigational research agents within 30 days prior to study entry;

Sponsors & Collaborators

• Societa' Italiana Di Malattie Infettive E Tropicali: lead

Study Sites (25)

Azienda Ospedaliera Universitaria Policlinico di Bari

Bari, BA, 70124, Italy

ACTIVE NOT RECRUITING

ASST Papa Giovanni XXIII

Bergamo, BG, 24127, Italy

NOT YET RECRUITING

ARNAS Garibaldi

Catania, CT, 95123, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria Ferrara

Ferrara, FE, 44124, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, FI, 50134, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, FI, 50134, Italy

NOT YET RECRUITING

Ospedale Policlinico San Martino di Genova

Genova, GE, 16132, Italy

NOT YET RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

ACTIVE NOT RECRUITING

IRCCS Ospedale San Raffaele

Milan, MI, 20127, Italy

RECRUITING

ASST Fatebenefratelli Sacco

Milan, MI, 20131, Italy

NOT YET RECRUITING

ASST Fatebenefratelli Sacco

Milan, MI, 20131, Italy

NOT YET RECRUITING

ASST Santi Paolo e Carlo - Presidio San Paolo

Milan, MI, 20142, Italy

NOT YET RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, MI, 20162, Italy

ACTIVE NOT RECRUITING

Ospedale San Gerardo di Monza

Monza, MI, 20900, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria di Modena

Modena, MO, 41124, Italy

NOT YET RECRUITING

A.O.U. Policlinico "Paolo Giaccone"

Palermo, PA, 90127, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera di Padova

Padua, PD, 35128, Italy

NOT YET RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, 27100, Italy

NOT YET RECRUITING

Policlinico Universitario Tor Vergata

Roma, RM, 00133, Italy

ACTIVE NOT RECRUITING

Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS

Roma, RM, 00149, Italy

RECRUITING

A.O.U. Policlinico Umberto I

Roma, RM, 00155, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, RM, 00168, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Universitaria Senese

Siena, SI, 53100, Italy

ACTIVE NOT RECRUITING

Strutture Ospedaliere - Cliniche San Pietro - AOU Sassari

Sassari, SS, 07100, Italy

ACTIVE NOT RECRUITING

Ospedale Amedeo di Savoia

Torino, TO, 10149, Italy

NOT YET RECRUITING

Related Links

• eCRF Home page

MeSH Terms

Interventions

dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Andrea Andreoni, P.I.

  Policlinico Universitario Tor Vergata

  PRINCIPAL INVESTIGATOR

• Alessandra Bandera, P.I.

  Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

  PRINCIPAL INVESTIGATOR

• Alessandro Bartoloni, P.I.

  Azienda Ospedaliero-Universitaria Careggi

  PRINCIPAL INVESTIGATOR

• Stefano Bonora, P.I.

  Ospedale Amedeo di Savoia

  PRINCIPAL INVESTIGATOR

• Antonio Cascio, P.I.

  A.O.U. Policlinico "Paolo Giaccone"

  PRINCIPAL INVESTIGATOR

• Antonella Castagna, P.I.

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

• Annamaria Cattelan, P.I.

  Azienda Ospedaliera di Padova

  PRINCIPAL INVESTIGATOR

• Roberto Cauda, P.I.

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

• Benedetto Maurizio Celesia, P.I.

  ARNAS Garibaldi

  PRINCIPAL INVESTIGATOR

• Antonella d'Arminio Monforte, P.I.

  ASST Santi Paolo e Carlo - Presidio San Paolo

  PRINCIPAL INVESTIGATOR

• Antonio Di Biagio, P.I.

  Ospedale Policlinico San Martino di Genova

  PRINCIPAL INVESTIGATOR

• Massimo Antonio Di Pietro, P.I.

  Azienda Ospedaliero-Universitaria Careggi

  PRINCIPAL INVESTIGATOR

• Massimiliano Fabbiani, P.I.

  Azienda Ospedaliera Universitaria Senese

  PRINCIPAL INVESTIGATOR

• Roberto Gulminetti, P.I.

  Fondazione IRCCS Policlinico San Matteo

  PRINCIPAL INVESTIGATOR

• Giuseppe Lapadula, P.I.

  Ospedale San Gerardo di Monza

  PRINCIPAL INVESTIGATOR

• Giordano Madeddu, P.I.

  Strutture Ospedaliere - Cliniche San Pietro - AOU Sassari

  PRINCIPAL INVESTIGATOR

• Franco Maggiolo, P.I.

  ASST Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

• Cristina Mussini, P.I.

  Azienda Ospedaliero-Universitaria di Modena

  PRINCIPAL INVESTIGATOR

• Massimo Puoti, P.I.

  ASST Grande Ospedale Metropolitano Niguarda

  PRINCIPAL INVESTIGATOR

• Giuliano Rizzardini, P.I.

  ASST Fatebenefratelli Sacco

  PRINCIPAL INVESTIGATOR

• Stefano Rusconi, P.I.

  ASST Fatebenefratelli Sacco

  PRINCIPAL INVESTIGATOR

• Annalisa aracino, P.I.

  Azienda Ospedaliera Universitaria Policlinico di Bari

  PRINCIPAL INVESTIGATOR

• Laura Sighinolfi, P.I.

  Azienda Ospedaliera Universitaria Ferrara

  PRINCIPAL INVESTIGATOR

• Gabriella d'Ettorre, P.I.

  A.O.U. Policlinico Umberto I

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Antinori, P.I.

CONTACT

0655170546; andrea.antinori@inmi.it

Maddalena Plazzi, DM

CONTACT

3384093449; maria.plazzi@inmi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, randomized, open-label, multicentre, active-controlled, non-inferiority study evaluating the efficacy and safety of early switching to dolutegravir/lamivudine (DTG/3TC) in single-pill, in HIV-1 infected individuals currently taking an INSTI-based three-drug first-line regimen for less than 18 months and who have been virologically suppressed with HIV-1 RNA \<50 copies/mL

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 28, 2021
• Study Start: March 23, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2024
• Last Updated: July 28, 2021

Record last verified: 2021-07

Locations

IT (25)