Clinical trial NCT04429152: ADORE: Efficacy of DORavirine in Adults Living With HIV Experiencing Virological Failure on First-line Efavirenz-based Antiretroviral Therapy With NNRTI Resistance
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HIV-1-infection
Keywords: Virological failure, first-line antiretroviral therapy
Doravirine
Delstrigo
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
First posted: 2020-06-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at week 24
timeFrame: 24 weeks
Secondary outcomes:
measure: Proportion of patients with undetectable plasma HIV-1 RNA levels (<50 copies/mL) at weeks 4, 12 and 48
timeFrame: At week 4, 12, 48
measure: Change from baseline in plasma CD4 levels at weeks 24 and 48
timeFrame: At week 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
city: Johannesburg
country: South Africa
facility: Wits RHI Yeoville Clinic
state: Gauteng
Study officials:
affiliation: Ezintsha, a subdivision of Wits Reproductive Health and HIV Institute (Wits RHI)
name: Simiso Sokhela, MBBCh
role: PRINCIPAL_INVESTIGATOR
References: