Clinical Trials

MainTitle

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

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified May 2020 by Daniel Podzamczer, Fundacio Lluita Contra la SIDA

Sponsor
Fundacio Lluita Contra la SIDA

Collaborator
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge

Information provided by (Responsible Party)
Daniel Podzamczer, Fundacio Lluita Contra la SIDA

ClinicalTrials.gov Identifier
NCT04079452

First received: September 3, 2019
Last updated: May 5, 2020
Last Verified: May 2020
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV-1-infection

Drug : Doravirine
Drug : Descovy
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals

Further study details as provided by Daniel Podzamczer, Fundacio Lluita Contra la SIDA:

Primary Outcome Measures

  • Doravirine concentrations in CSF [ Time Frame: 4 Weeks ]
    To determine total and unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF
  • Doravirine concentrations in blood plasma [ Time Frame: 4 Weeks ]
    Total Doravirine concentrations in blood plasma
  • Doravirine CSF/plasma ratio [ Time Frame: 4 Weeks ]
    Doravirine CSF/plasma ratio
  • HIV-1 RNA in cerebrospinal fluid [ Time Frame: 4 Weeks ]
    HIV-1 RNA in cerebrospinal fluid
  • HIV-1 RNA in blood plasma [ Time Frame: 4 Weeks ]
    HIV-1 RNA in blood plasma

Estimated Enrollment: 15
Anticipated Study Start Date: June 2020
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: July 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 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
Drug: Doravirine

Doravirine 100 mg tablet

Other Name: MK-1439
Drug: Descovy

Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Other Name: TAF/FTC

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

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT04079452

Contacts

Contact:   Juan Manuel Tiraboschi, PhD +34932607667 ext 2885 jmtiraboschi@bellvitgehospital.cat
Contact:   Arkaitz Imaz, PhD +34932607667 ext 2883 aimaz@bellvitgehospital.cat

Locations

Spain
Hospital Universitari de Bellvitge
L'Hospitalet De Llobregat, Barcelona, Spain, 08907
Contact: Camila Piatti    +34933359011 ext 2876    cpiatti@bellvitgehospital.cat
Contact: Laura Acerete    +34933359011 ext 2876    lacerete@bellvitgehospital.cat
Principal Investigator: Daniel Podzamczer, PhD
Sub-Investigator: Juan Manuel Tiraboschi, PhD
Sub-Investigator: Arkaitz Imaz, PhD

Sponsors and Collaborators

Fundacio Lluita Contra la SIDA
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge

Investigators

Principal Investigator: Daniel Podzamczer, PhD Chief Hospital Universitari de Bellvitge
More Information

More Information


Responsible Party: Daniel Podzamczer, PhD: chief of the HIV and STD Unit (Infectious Disease Service), Fundacio Lluita Contra la SIDA  
ClinicalTrials.gov Identifier: NCT04079452   History of Changes  
Other Study ID Numbers: DORACeNeS  
  2018-003915-24  
Study First Received: September 3, 2019  
Last Updated: May 5, 2020  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Daniel Podzamczer, Fundacio Lluita Contra la SIDA:

Doravirine

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.