Clinical trial NCT04097925: Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals
Official title: Doravirine Concentrations and Antiviral Activity in Genital Fluids in HIV-1 Infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1-infection
Keywords: Doravirine
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Sponsor class: OTHER
Collaborators: name: Institut d'Investigació Biomèdica de Bellvitge
name: Hospital Universitari de Bellvitge
First posted: 2019-09-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with Doravirine administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) co-formulated as single tablet (Descovy® TAF/FTC) and administered orally once daily.
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Concentration of Doravirine in Seminal Plasma Fluid
timeFrame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
measure: Concentration of Doravirine in Cervicovaginal Fluid
timeFrame: 8 weeks after switching to Doravirine plus TAF/FTC
measure: Number of Participants With HIV-1 RNA Seminal Plasma <40 Copies/mL
timeFrame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
measure: Quantification of Participants With HIV-1 RNA <40 Copies / mL in Cervicovaginal Fluid
timeFrame: 8 weeks after switching (from baseline visit) to Doravirine plus TAF/FTC
Secondary outcomes:
Other outcomes:
Locations:
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
Study officials:
affiliation: Hospital Universitari de Bellvitge
name: Daniel Podzamczer Palter, PhD Chief
role: PRINCIPAL_INVESTIGATOR
References: