ADORE: Efficacy of DORavirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With NNRTI Resistance (ADORE)

ADORE: A Single-arm, Phase 3, Pilot Study Investigating the Efficacy of Doravirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With Non-nucleoside Reverse Transcriptase Inhibitor Resistance

This is a pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance

Study Overview

• Status: Recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Doravirine/Lamivudine/Tenofovir

Detailed Description

This is a single-arm, phase 3 pilot study investigating the efficacy of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in adults living with HIV-1 experiencing virological failure on first-line Efavirenz-based antiretroviral therapy with non-nucleoside reverse transcriptase inhibitor resistance.

Approximately 25 male and female participants 18 years and older infected with HIV-1 and experiencing virological failure on efavirenz-based ART will be administered a once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF). The study includes screening and baseline visits, 4 study visits from Week 4 to Week 36, and an end of study visit at Week 48.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Simiso Sokhela, MBBCh; Phone Number: +27113585437; Email: ssokhela@wrhi.ac.za

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • Recruiting
      • Charlotte Maxeke Johannesburg Academic Hospital
      • Contact: Natasha Arulappan; Phone Number: +27113585542; Email: gakpomiemie@wrhi.ac.za
      • Contact: Nonkululeko Mashabane, BPharm; Phone Number: +27113585543
    • Johannesburg, Gauteng, South Africa
      • Not yet recruiting
      • Sunnyside Office Park
    • Johannesburg, Gauteng, South Africa
      • Not yet recruiting
      • Wits RHI Yeoville Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults living with HIV-1, 18 years and older
• Viral load 5000 - 60 000 copies/mL on first-line efavirenz-based antiretroviral therapy
• HIV genotype resistance test with first generation NNRTI resistance (e.g. K103N, Y181C, etc as listed in the protocol)
• CD4 > 200 cells/uL
• Creatinine clearance > 50 mL/min
• Body mass ≥ 35 kg.

Exclusion Criteria:

• Resistance to TDF on genotype (K65R)
• "Significant resistance" to doravirine, denoted by a Stanford Score ≥ 15 on genotype
• Virologic failure on any other regimen
• Women who are pregnant at the time of the screening or enrolment visits
• Active tuberculosis and/or are on anti-tuberculous therapy at the time of the screening or enrolment visits
• Taking and cannot discontinue prohibited concomitant medications listed in protocol at least two weeks prior to the enrolment visit and for the duration of the study period.

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: Doravirine; Once-daily, fixed-dose combination of doravirine 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF).	Drug: Doravirine/Lamivudine/Tenofovir; DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination; Other Names: Delstrigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24	The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 24 will be recorded.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48	Evaluation of viral suppression by recording the proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48	At week 4, 12, 48
Change from baseline in plasma CD4 levels at weeks 24 and 48	Evaluation of changes in CD4 count from baseline recorded at weeks 24 and 48.	At week 24, 48
Emergence of antiretroviral resistance mutations in participants with virological failure	Evaluation of the number of antiretroviral resistance mutations that emerge in participants with virological failure	48 weeks

Collaborators and Investigators

• Sponsor: Professor Francois Venter

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 7, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Doravirine; Virological failure, first-line antiretroviral therapy; Delstrigo
• 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: EZMiM018

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