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

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Societa' Italiana Di Malattie Infettive E Tropicali
• Treatments: Dolutegravir; Lamivudine

Criteria

Inclusion Criteria:

• 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;

• Not breastfeeding;

• Of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy;

• Of childbearing potential and agrees to utilize the protocol specified method of contraception (as defined in Appendix 1 -Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential) or be non-heterosexually active or practice sexual abstinence (defined as complete abstinence from penile-vaginal intercourse; periodic abstinence, e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) from screening throughout the duration of study treatment and for at least two weeks following discontinuation of study drugs;

• Being able to comply with the protocol requirements and restrictions;

• Signature of written Informed Consent Form (participants or legal guardian) before that any protocol-specified assessments are conducted.

Exclusion Criteria:

A person will be considered not eligible for inclusion in this study if any of the following criteria apply:

• 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;

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening;

• Receipt of immunosuppressive medications or immune-modulators within the past 6 months;

• Individuals who in the investigator's judgment, poses a significant suicidality risk or with diagnosed major depression, Bipolar Disorders and Psychoses

• A life expectancy estimated as less than 2 years.