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

NCT04433780 | Completed Phase 3 DMC

• 1 other identifier: EZMiM017
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV-1-infection

Keywords

Doravirine; Delstrigo; DOR/3TC/TDF; Women of reproductive potential

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (10)

• The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)

  At week 24, 48

• The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories

  24 weeks

• Changes in glucose from baseline to week 24

  24 weeks

• Changes in fasting lipids from baseline to week 24

  24 weeks

• Changes in weight and from baseline to week 24

  24 weeks

Study Arms (1)

Delstrigo

EXPERIMENTAL

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

Interventions

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate DRUG

DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC

Also known as: Delstrigo

Delstrigo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Female HIV-positive participants of reproductive potential age
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Professor Francois Venter: lead

Study Sites (2)

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, Gauteng, 2196, South Africa

Location

Sunnyside Office Park

Johannesburg, Gauteng, South Africa

Location

MeSH Terms

Interventions

doravirine

Study Officials

• Simiso Sokhela

  Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Divisional Director of Ezintsha

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 16, 2020
• Study Start: January 4, 2021
• Primary Completion: February 20, 2023
• Study Completion: March 31, 2023
• Last Updated: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Immediately following publication
• Access Criteria: Anyone who wishes to access the data

Locations

ZA (2)