Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals

NCT ID: NCT04079452

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-18
• Study Completion Date: 2020-08-31

Brief Summary

Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated a good efficacy and safety profile in clinical trials. It functions by inhibiting viral replication of both wild-type virus and most common NNRTI variants. It is dosed orally once daily and always given in combination with other HIV-1 active agents as part of highly active antiretroviral therapy. Initial pharmacokinetic studies demonstrated not extensive binding to plasma proteins, which may be crucial determinant for penetration to different reservoirs such as the central nervous system (CNS). This study will address two important issues: The pharmacokinetic profile of Doravirine in cerebrospinal fluid (CSF) as well as the maintenance of HIV suppression in CSF. The assessment of concentrations as well as the antiviral activity of new antiretroviral drugs in compartments such as CNS is relevant to avoid HIV-related neurocognitive disorders as well as for future cure strategies. In addition, the role of unbound ARV drug concentrations has been scarcely evaluated.

Detailed Description

15 asymptomatic, virologically suppressed, HIV infected patients will be offered to switch their antiretroviral treatment to Doravirine+Emtricitabine/TAF. After 4 weeks of treatment all subjects will undergo lumbar puncture and bloods in order to assess CSF and plasma (total and unbound) Doravirine concentrations. HIV RNA also will be assessed. All subjects will complete a follow up visit 4 weeks after

Conditions

HIV-1-infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doravirine + Descovy® TAF/FTC

Doravirine (MK-1439) 100 mg administered orally once daily in combination with Tenofovir alafenamide (TAF) and emtricitabine (FTC) coformulated as single tablet (Descovy® TAF/FTC 25/200 mg) and administered orally once daily during 4 weeks

Group Type: EXPERIMENTAL

Doravirine

Intervention Type: DRUG

Doravirine 100 mg tablet

Descovy

Intervention Type: DRUG

Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Interventions

Doravirine

Doravirine 100 mg tablet

Intervention Type: DRUG

Descovy

Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Intervention Type: DRUG

Other Intervention Names

MK-1439; TAF/FTC

Eligibility Criteria

Inclusion Criteria

1. Asymptomatic, HIV-1 infected individuals ≥ 18 years of age

2. Be on a stable ART continously or ≥3 consecutive months preceding the screening visit. Patients already receiving TAF/FTC+DoravirineC for at least three consecutive months will be eligible.

3. Plasma HIV-1 RNA at screening <40 copies/mL for at least 3 months at the Screening visit.

4. Signed and dated written informed consent prior to inclusion.

5. Subjects 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. Primary resistance to any of the 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. Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min

8. Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.

9. Current treatment with antiaggregant or anticoagulant therapy.

10. History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut d'Investigació Biomèdica de Bellvitge

OTHER

Sponsor Role: collaborator

Hospital Universitari de Bellvitge

OTHER

Sponsor Role: collaborator

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: lead

Responsible Party

Daniel Podzamczer

PhD: chief of the HIV and STD Unit (Infectious Disease Service)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Podzamczer, PhD Chief

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitari de Bellvitge

Locations

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Countries

Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2018-003915-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DORACeNeS

Identifier Type: -

Identifier Source: org_study_id