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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delstrigo<br>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<br>* DOR/3TC/TDF 100/300/300 mg once daily fixed-dose combination switched from either EFV/TDF/FTC or DTG/TDF/3TC<br>* Other names: Delstrigo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Doravirine, Delstrigo, DOR/3TC/TDF, Women of reproductive potential