DORA: A Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV (DORA)

A Single Arm, Phase 3 Study, Exploring the Safety of Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV, a Pilot Switch Study Strategy in South Africa

This is a pilot study investigating the safety of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy on metabolic and neuropsychiatric outcomes.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate

Detailed Description

This is a pilot, open label, single-arm, single centre, phase 3, switch study exploring the safety of of Doravirine (DOR) in combination with Lamivudine (3TC) and Tenofovir Disoproxil Fumarate (TDF) administered over 48 weeks in women of reproductive potential living with HIV-1 switched from Efavirenz or Dolutegravir-based antiretroviral therapy. The metabolic and neuropsychiatric outcomes among women (and their infants) in a representative African female population of reproductive potential will be investigated.

Approximately 100 women aged between 18 and 49 years old 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 (Actual): 133
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa
      • Sunnyside Office Park
    • Johannesburg, Gauteng, South Africa, 2196
      • Charlotte Maxeke Johannesburg Academic Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females, aged 18-49 years and ≥ 40 kg
• On a first-line EFV or DTG-containing regimen for at least six months and not more than 3 years
• Plasma HIV-1 RNA < 50 copies/mL in last 60 days
• Calculated creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault formula)
• Baseline weight measurement available at ART initiation.

Exclusion Criteria:

• Virological failure on any other regimen
• Women who are pregnant at the time of the screening or enrolment visits or have had a pregnancy gestation ≥ 28 weeks in the preceding 2 years
• Active tuberculosis and/or are on antituberculosis 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 (see potential drug interactions section for list).

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: Delstrigo; 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 Disoproxil Fumarate; DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC; Other Names: Delstrigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with neuropsychiatric adverse events (AEs)	The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 48	48 weeks
Changes in fasting lipids from baseline to Week 48	Changes in fasting lipids from baseline to Week 48 assessed using lipid profile blood test	48 weeks
Changes in weight from baseline to Week 48	Changes in weight from baseline to Week 48 assessed	48 weeks
Changes in body mass index from baseline to Week 48	Changes in body mass index from baseline to Week 48 assessed	48 weeks
Changes in glucose from baseline to Week 48	Changes in glucose from baseline to Week 48 assessed using blood test	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)	The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL) at weeks 24 and 48	At week 24, 48
The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories	The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories (dizziness, sleep disorders/ disturbances, and altered sensorium) at Week 24	24 weeks
Changes in glucose from baseline to week 24	Changes in glucose from baseline to Week 24 using blood test	24 weeks
Changes in fasting lipids from baseline to week 24	Changes in fasting lipids from baseline to Week 24 using lipid profile blood test	24 weeks
Changes in weight and from baseline to week 24	Changes in weight from baseline to Week 24	24 weeks
Changes in body mass index from baseline to week 24	Changes in body mass index from baseline to Week 24	24 weeks
The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)	The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)	48 weeks
Changes in quality of life from baseline	Changes in quality of life from baseline to Weeks 24 and 48 measured using a traditional clinical, validated quality of life questionairre. Higher scores mean a better outcome	At weeks 24, 48
Median adherence by each adherence measure	Median adherence by each adherence measure at Weeks 24 and 48 using a validated adherence questionairre	At weeks 24, 48
Emergence of antiretroviral resistance mutations in participants with virological failure	Evaluating the number of antiretroviral resistance mutations that emerge in participants with virological failure	48 weeks

Collaborators and Investigators

• Sponsor: Professor Francois Venter
• Investigators: Principal Investigator: Simiso Sokhela, Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Actual): February 20, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Doravirine; Delstrigo; DOR/3TC/TDF; Women of reproductive potential
• 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: EZMiM017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.The data that will be shared is all of the individual participant data collected during the trial, after identification. The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Immediately following publication
• IPD Sharing Access Criteria: Anyone who wishes to access the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No