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

NCT04079452 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: DORACeNeS2018-003915-24
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1-infection

Keywords

Doravirine

Outcome Measures

Primary Outcomes (8)

• Total Doravirine Concentrations in Cerebrospinal Fluid

  Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  4 Weeks

• Total Doravirine Concentrations in Blood Plasma

  Total Doravirine concentrations in blood plasma

  4 Weeks

• Total Doravirine Concentration CSF/Plasma Ratio

  total Doravirine CSF/plasma ratio

  4 Weeks

• HIV-1 RNA in Cerebrospinal Fluid

  Number of patients with HIV-1 RNA cerebrospinal fluid \<40 copies/ml

  4 Weeks

• HIV-1 RNA in Blood Plasma

  Number of patients with HIV-1 RNA in blood plasma \<40 copies/ml

  4 Weeks

• Unbound Doravirine Concentrations in CSF

  Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  4 Weeks

• Doravirine Concentrations in Blood Plasma

  Unbound Doravirine concentrations in blood plasma

  4 Weeks

• Unbound Doravirine Concentration CSF/Plasma Ratio

  Unbound Doravirine CSF/plasma ratio

  4 Weeks

Study Arms (1)

Doravirine + Descovy® TAF/FTC

EXPERIMENTAL

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

Drug: Doravirine; Drug: Descovy

Interventions

Doravirine DRUG

Doravirine 100 mg tablet

Also known as: MK-1439

Doravirine + Descovy® TAF/FTC

Descovy DRUG

Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Also known as: TAF/FTC

Doravirine + Descovy® TAF/FTC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Asymptomatic, HIV-1 infected individuals ≥ 18 years of age
• 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.
• Plasma HIV-1 RNA at screening \<40 copies/mL for at least 3 months at the Screening visit.
• Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.

You may not qualify if:

• Severe hepatic impairment (Child-Pugh Class C)
• Ongoing malignancy
• Active opportunistic infection
• 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.
• Any verified Grade 4 laboratory abnormality
• ALT or AST ≥ 3xULN and/or bilirubin ≥ 1.5xULN
• Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min
• Females who are pregnant (as confirmed by positive serum pregnancy test) or breastfeeding.
• Current treatment with antiaggregant or anticoagulant therapy.
• History of any neurologic disease/condition/treatment may alter the blood brain barrier permeability.

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• Institut d'Investigació Biomèdica de Bellvitge: collaborator
• Hospital Universitari de Bellvitge: collaborator

Study Sites (1)

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

MeSH Terms

Interventions

doravirine; emtricitabine tenofovir alafenamide

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Hospital de Bellvitge

anavarroa@bellvitgehospital.cat

+34675335888

Study Officials

• Daniel Podzamczer, PhD Chief

  Hospital Universitari de Bellvitge

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD: chief of the HIV and STD Unit (Infectious Disease Service)

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: February 18, 2020
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: April 28, 2022
• Results First Posted: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)