Women in Dual With Dolutegravir (Woddol4455)

Multi-center Study to Evaluate Virological Efficacy, Safety Tolerability, Drug Exposure and Patients' Reported Outcomes Over 48 Weeks Following Randomization to 2-drug Therapy With DTG/3TC FDC or Continuing Current Antiretroviral Tenofovir (TAF or TDF)-Containing Regimen (T-CR) in HIV-1 Infected Virologically Suppressed

Strategies for optimizing antiretroviral treatment in virologically suppressed patients are still a major challenge in the field of HIV. These strategies include improving the toxicity and tolerability of drugs in the short and long term, such as replacing toxic agents with safer ones or reducing the number of drugs in the combination. Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir (TFV) that is converted intracellularly to the active form, resulting in higher concentrations of TFV diphosphate in circulating lymphocytes than those obtained with tenofovir disoproxil fumarate (TDF). Because of these pharmacokinetic properties, TAF results in 91% lower plasma exposure to TFV. Phase 3 studies have established the virological noninferiority of TAF to TDF, with a lower frequency of renal and bone adverse events. Replacing TDF with TAF may be a safe and effective option to reduce toxicities when switching from one ARV strategy to another and, to date, could represent the optimization of a three-drug regimen. Dolutegravir (DTG) is a potent INSTI that exhibits rapid and potent viral load reduction and a high barrier to resistance.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Antiviral Agents

• Study Type: Interventional
• Enrollment (Estimated): 290
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione PoliclinicoAgostino Gemelli IRCCS
    • Contact: Antonella Cingolani; Phone Number: 00390630154945; Email: antonella.cingolani@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female individuals
• HIV-1 documented infection
• Age > 18 years
• Being on an effective (pVL < 50 copies/ml) three-drug cART regimen containing tenofovir (TAF or TDF) (e.g. TAF/F/E/C; TAF/F/RPV; TDF/F/RPV; TAF/F+PI/C; TDF/F/PI/c; TAF/F+PI/r; TDF/F/PI/r; TAF/F+DTG; TDF/F/DTG; TAF/F+RTG; TDF/F/RTG; TAF/F/BIC) for at least 3 months before the screening. Two consecutive HIV-1 RNA determinations below the determination threshold before enrollment are required
• No known allergy or intolerance to NRTIs, NNRTIs or INSTIs
• Women of childbearing potential will be required to adopt an effective birth control system throughout the study period
• Subjects able to comply with the protocol requirements
• Informed consent signed

Exclusion Criteria:

• Having failed virologically any previous ART regimen · Evidence of any 3TC (presence of M184V/I or K65R/E/N) or INSTI resistance · Having ever been treated with mono or dual ARV therapies subsequently intensified to three-drug cART regimen
• Pregnancy or breast-feeding or not willing to use effective contraception if they are of child bearing potential
• An active malignancy or OI requiring active treatment (prophylactic regimens are allowed) · HBV infection · A life expectancy < 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3TC/DTG; ·To evaluate efficacy of switching to a two-drug one-pill regimen with DTG/3TC	Drug: Antiviral Agents; two-drug one-pill once day
Active Comparator: TDF Regimen; comparision arm to maintaining the three-drugs regimen in women currently receiving any three-drug regimen containing Tenovofir (TAF or TDF) (e.g. TAF/F/E/C; TAF/F/RPV; TDF/F/RPV; TAF/F+PI/C; TAF/F+PI/r; TDF/F/PI/r; TAF/F+DTG; TDF/F/DTG; TAF/F+RTG; TDF/F/RTG; TAF/F/BIC) who are virologically suppressed.	Drug: Antiviral Agents; two-drug one-pill once day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-RNA < 50 copies/ml	Proportion of patients maintaining a HIV-RNA < 50 copies/ml according to FDA snapshot algorithm at 48 weeks according to an ITT NC = failure approach in which all randomized patients will be included and considered failures independently of the reason they did not complete the follow-up.	96 weeks

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): September 15, 2025
• Study Completion (Estimated): September 15, 2025

Study Registration Dates

• First Submitted: February 1, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Anti-Infective Agents; Antiviral Agents
• Other Study ID Numbers: 4455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No