Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals

Phase 2

Completed

• Conditions: HIV-1-infection
• Interventions: Drug: Doravirine; Drug: Descovy

• Registration Number: NCT04097925
• Lead Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Brief Summary

This study aims to evaluate the ability of Doravirine to penetrate the genital tract and suppress viral replication and provide evidence for the use of Doravirine as part of treatment strategies as prevention.

Detailed Description

Objectives:

* To determine Doravirine concentrations in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving antiretroviral therapy (ATR) with Doravirine plus Descovy®.

* To evaluate HIV-1 viral load in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals receiving ART with Doravirine plus Descovy®.

Study Phase:

Phase II

Study Design:

Open label, single arm, single center, prospective study.

Study Disease:

HIV-1 infection

Study Endpoints:

* Concentration of Doravirine in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®.

* HIV-1 RNA in seminal plasma and cervicovaginal fluid in HIV-1 infected male and female individuals, respectively, 8 weeks after switching to Doravirine plus Descovy®.

Target Population:

Male and female adult HIV-1 infected patients receiving standard ART with tenofovir alafenamide/emtricitabine (TAF/FTC), tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine , plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor during at least 3 months, with plasma HIV-1 RNA suppression (\<40 copies/mL) during at least 6 months.

Number of Subjects Planned:

15 male and 15 female individuals.

Study duration:

16 weeks

Study Timeline

• Study First Submitted: 2019-09-18
• Study First Submitted QC: 2019-09-19
• Study First Posted: 2019-09-20
• Study Start: 2020-02-18
• Primary Completion: 2020-08-24
• Study Completion: 2020-08-24
• Results First Submitted: 2022-02-27
• Results First Submitted QC: 2022-05-24
• Results First Posted: 2022-05-25
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-15
• Last Update Posted: 2022-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Asymptomatic, HIV-1 infected individuals ≥ 18 years of age.
2. Be on a stable ART consisting of TAF/FTC, tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor, continuously for at least 3 consecutive months preceding the screening visit.
3. Plasma HIV-1 RNA <40 copies/mL for at least 6 months at the Screening visit.
4. Signed and dated written informed consent prior to inclusion.
5. Female Subjects of Childbearing Potential must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.

Exclusion Criteria

1. Severe hepatic impairment (Child-Pugh Class C)
2. Ongoing malignancy
3. Active opportunistic infection
4. Resistance to any of the antiretroviral (ARV) included in the study or history of virologic failure with risk of resistance selection to any of the study drugs.
5. Any verified Grade 4 laboratory abnormality
6. ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN
7. Severe renal impairment (Estimated creatinine filtration rate <50mL/min).
8. Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Doravirine + Descovy® TAF/FTC	Descovy	Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 16 weeks
Doravirine + Descovy® TAF/FTC	Doravirine	Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 16 weeks

Primary Outcome Measures

Name	Time	Method
Concentration of Doravirine in Seminal Plasma Fluid	8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC	Concentration of Doravirine in seminal plasma fluid in HIV-1 infected male individuals
Concentration of Doravirine in Cervicovaginal Fluid	8 weeks after switching to Doravirine plus TAF/FTC	Concentration of Doravirine in cervicovaginal fluid in HIV-1 infected female individuals
Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL	8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC	Number of participants with HIV-1 RNA seminal plasma \<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification
Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid	8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC	Number of participants with HIV-1 RNA cervicovaginal fluid\<40 Copies / mL of HIV measured by real-Time Reverse Transcriptase Polymerase Chain Reaction Amplification

Trial Locations

Locations (1)

Hospital Universitari de Bellvitge; 🇪🇸 L'Hospitalet De Llobregat, Barcelona, Spain