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

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ClinicalTrials.gov Identifier: NCT04079452
Recruitment Status : Not yet recruiting
First Posted : September 6, 2019
Last Update Posted : December 26, 2019
Sponsor:
Collaborators:
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge
Information provided by (Responsible Party):
Daniel Podzamczer, Fundacio Lluita Contra la SIDA

Tracking Information
First Submitted Date  ICMJE September 3, 2019
First Posted Date  ICMJE September 6, 2019
Last Update Posted Date December 26, 2019
Estimated Study Start Date  ICMJE January 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04079452 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals
Official Title  ICMJE Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1-infection
Intervention  ICMJE
  • Drug: Doravirine
    Doravirine 100 mg tablet
    Other Name: MK-1439
  • Drug: Descovy
    Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet
    Other Name: TAF/FTC
Study Arms  ICMJE 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
Interventions:
  • Drug: Doravirine
  • Drug: Descovy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 3, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Juan Manuel Tiraboschi, PhD +34932607667 ext 2885 jmtiraboschi@bellvitgehospital.cat
Contact: Arkaitz Imaz, PhD +34932607667 ext 2883 aimaz@bellvitgehospital.cat
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04079452
Other Study ID Numbers  ICMJE DORACeNeS
2018-003915-24 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel Podzamczer, Fundacio Lluita Contra la SIDA
Study Sponsor  ICMJE Fundacio Lluita Contra la SIDA
Collaborators  ICMJE
  • Institut d'Investigació Biomèdica de Bellvitge
  • Hospital Universitari de Bellvitge
Investigators  ICMJE
Principal Investigator: Daniel Podzamczer, PhD Chief Hospital Universitari de Bellvitge
PRS Account Fundacio Lluita Contra la SIDA
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP