Clinical trial NCT04433780: DORA: A Doravirine-based First-line Antiretroviral Therapy for Women of Reproductive Potential Living With HIV
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1-infection
Keywords: Doravirine
Delstrigo
DOR/3TC/TDF
Women of reproductive potential
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 133
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: The proportion of participants with neuropsychiatric adverse events (AEs)
timeFrame: 48 weeks
measure: Changes in fasting lipids from baseline to Week 48
timeFrame: 48 weeks
measure: Changes in weight from baseline to Week 48
timeFrame: 48 weeks
measure: Changes in body mass index from baseline to Week 48
timeFrame: 48 weeks
measure: Changes in glucose from baseline to Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: The proportion of participants with detectable plasma HIV-1 RNA levels (≥ 50 copies/mL)
timeFrame: At week 24, 48
measure: The proportion of participants with neuropsychiatric adverse events (AEs) in 3 pre-specified categories
timeFrame: 24 weeks
measure: Changes in glucose from baseline to week 24
timeFrame: 24 weeks
measure: Changes in fasting lipids from baseline to week 24
timeFrame: 24 weeks
measure: Changes in weight and from baseline to week 24
timeFrame: 24 weeks
measure: Changes in body mass index from baseline to week 24
timeFrame: 24 weeks
measure: The proportion of infants evaluated for HIV-positive tests using HIV DNA polymerase chain reaction test (PCR)
timeFrame: 48 weeks
measure: Changes in quality of life from baseline
timeFrame: At weeks 24, 48
measure: Median adherence by each adherence measure
timeFrame: At weeks 24, 48
measure: Emergence of antiretroviral resistance mutations in participants with virological failure
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Sunnyside Office Park
state: Gauteng
Study officials:
affiliation: Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
name: Simiso Sokhela
role: PRINCIPAL_INVESTIGATOR
References: