DOR/TDF/3TC Switch With M184V/I in People With Controlled HIV (Drive Off-Road) (DOR)

DOR/TDF/3TC Maintenance Therapy Among Patients Harboring M184V/I Mutation: a Pilot Open-label Study

The goal of this pilot, phase 2, single-arm, clinical trial is to assess the antiretroviral combination Doravirine (DOR)/Lamivudine (3TC)/Tenofovir Disproxyl Fumarate (TDF) in participants with suppressed HIV who previously developed M184V/I mutation that confers resistance to 3TC. The main question it aims to answer is to explore the rate of HIV suppression 24 weeks after the switch to DOR/3TC/TDF. The study follow-up will continue until 48 weeks. Other endpoints will be metabolic changes, weight changes, modification in the HIV-DNA mutations overtime. Eligible participants will switch from their prior regimen to DOR/3TC/TDF with careful HIV-RNA monitoring.

Study Overview

• Status: Not yet recruiting
• Conditions: Hiv
• Intervention / Treatment: Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jean-Jacques Parienti, MD, PhD; Phone Number: +33231064320; Email: parienti-jj@chu-caen.fr
• Study Contact Backup: Name: Francois Fournel, MSc; Email: fournel-f@chu-caen.fr

Study Locations

• France
  • Caen, France
    • CHU de Caen
  • Orléans, France
    • Chu Orleans
    • Contact: Laurent Hocqueloux, MD
    • Contact: Phone Number: +33238514444
  • Rouen, France
    • CHU Rouen
    • Contact: Manuel Etienne, MD, PhD; Phone Number: +33 232888990
  • Tourcoing, France
    • Ch Tourcoing
    • Contact: Olivier Robineau; Phone Number: +33 320694949

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult living with HIV
• Receiving stable antiretroviral treatment for at least 3 months
• HIV RNA VL<50cp/mL for at least 6 months
• Presence of the M184V/I mutation in at least one previous genotype performed on plasma HIV RNA but absent from the genotype on current standard pro-viral DNA (Sanger technique)
• Signed informed consent

Exclusion Criteria:

• History of genotypic mutation associated with resistance to DOR or TDF according to the ANRS version 32 algorithm, i.e. :
• For DOR : V106A/M; Y188L; G190E/S; M230L; L100I + K103N; K103N + Y181C; K103N + P225H; F227C; At least 3 amongst: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y
• For TDF : At least 3 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F; K65R/E/N ; Insertion at codon 69; K70E
• Contraindications to the use of DOR/TDF/3TC
• Hypersensitivity to doravirine, tenofovir, lamivudine or any of the excipients (lactose in particular)
• Current or recent treatment with a strong CYP3A4 inducer
• Breast-feeding
• Patients already on DOR
• Pregnant or breast-feeding women
• Patients under guardianship or trusteeship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm DOR/3TC/TDF; Doravirine 100 mg Lamivudine 300 mg Tenofovir disoproxil fumarate 245 mg Delstrigo (R): 1 pill/day for 48 weeks	Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate 100 MG-300 MG-300 MG Oral Tablet [DELSTRIGO]; Switch previous therapy with DOR/TDF/3TC; Other Names: Delstrigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma HIV-RNA at 24-week	Number of copies/mL	24 weeks from the switch to DOR/3TC/TDF

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma HIV-RNA at 48-week	Number of copies/mL	48 weeks from the switch to DOR/3TC/TDF

Collaborators and Investigators

• Sponsor: University Hospital, Caen
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Maintenance therapy; PLWH; doravirine; M184 mutation
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Lamivudine
• Other Study ID Numbers: MISP-RC_Parienti007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Contact principal investigator
• IPD Sharing Time Frame: 2-year after publishing the princeps study
• IPD Sharing Access Criteria: Relevant scientific question with protocol
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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