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

HIV-1-infection Clinical Trial

— DORA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04433780
• Other study ID #: EZMiM017
• Status: Completed
• Phase: Phase 3
• Start date: January 4, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: July 2023
• Source: University of Witwatersrand, South Africa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: March 31, 2023
• Est. primary completion date: February 20, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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).

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

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

Locations

Country	Name	City	State
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Johannesburg	Gauteng
South Africa	Sunnyside Office Park	Johannesburg	Gauteng

Sponsors (1)

Lead Sponsor	Collaborator
Professor Francois Venter

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Changes in weight from baseline to Week 48	Changes in weight from baseline to Week 48 assessed	48 weeks
Primary	Changes in body mass index from baseline to Week 48	Changes in body mass index from baseline to Week 48 assessed	48 weeks
Primary	Changes in glucose from baseline to Week 48	Changes in glucose from baseline to Week 48 assessed using blood test	48 weeks
Secondary	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
Secondary	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
Secondary	Changes in glucose from baseline to week 24	Changes in glucose from baseline to Week 24 using blood test	24 weeks
Secondary	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
Secondary	Changes in weight and from baseline to week 24	Changes in weight from baseline to Week 24	24 weeks
Secondary	Changes in body mass index from baseline to week 24	Changes in body mass index from baseline to Week 24	24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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