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

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04097925
• Other study ID #: DORAGEN
• Secondary ID: 2018-003921-27
• Status: Completed
• Phase: Phase 2
• Start date: February 18, 2020
• Est. completion date: August 24, 2020

Study information

• Verified date: June 2022
• Source: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 24, 2020
• Est. primary completion date: August 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Doravirine
Doravirine 100 mg tablet
• Descovy
Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Locations

Country	Name	City	State
Spain	Hospital Universitari de Bellvitge	L'Hospitalet De Llobregat	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia	Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge

Country where clinical trial is conducted

Spain, 

Outcome

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