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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04079452
Recruitment Status : Completed
First Posted : September 6, 2019
Results First Posted : April 28, 2022
Last Update Posted : April 28, 2022
Sponsor:
Collaborators:
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge
Information provided by (Responsible Party):
Daniel Podzamczer, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

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.

Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: Doravirine Drug: Descovy Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
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
Actual Study Start Date : February 18, 2020
Actual Primary Completion Date : August 31, 2020
Actual Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Doravirine

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Total Doravirine Concentrations in Cerebrospinal Fluid [ Time Frame: 4 Weeks ]
    Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  2. Total Doravirine Concentrations in Blood Plasma [ Time Frame: 4 Weeks ]
    Total Doravirine concentrations in blood plasma

  3. Total Doravirine Concentration CSF/Plasma Ratio [ Time Frame: 4 Weeks ]
    total Doravirine CSF/plasma ratio

  4. HIV-1 RNA in Cerebrospinal Fluid [ Time Frame: 4 Weeks ]
    Number of patients with HIV-1 RNA cerebrospinal fluid <40 copies/ml

  5. HIV-1 RNA in Blood Plasma [ Time Frame: 4 Weeks ]
    Number of patients with HIV-1 RNA in blood plasma <40 copies/ml

  6. Unbound Doravirine Concentrations in CSF [ Time Frame: 4 Weeks ]
    Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF

  7. Doravirine Concentrations in Blood Plasma [ Time Frame: 4 Weeks ]
    Unbound Doravirine concentrations in blood plasma

  8. Unbound Doravirine Concentration CSF/Plasma Ratio [ Time Frame: 4 Weeks ]
    Unbound Doravirine CSF/plasma ratio



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04079452


Locations
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Spain
Hospital Universitari de Bellvitge
L'Hospitalet De Llobregat, Barcelona, Spain, 08907
Sponsors and Collaborators
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Institut d'Investigació Biomèdica de Bellvitge
Hospital Universitari de Bellvitge
Investigators
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Principal Investigator: Daniel Podzamczer, PhD Chief Hospital Universitari de Bellvitge
  Study Documents (Full-Text)

Documents provided by Daniel Podzamczer, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia:
Study Protocol  [PDF] June 26, 2019
Statistical Analysis Plan  [PDF] June 26, 2019
Informed Consent Form  [PDF] April 10, 2019

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Responsible Party: Daniel Podzamczer, PhD: chief of the HIV and STD Unit (Infectious Disease Service), Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
ClinicalTrials.gov Identifier: NCT04079452    
Other Study ID Numbers: DORACeNeS
2018-003915-24 ( EudraCT Number )
First Posted: September 6, 2019    Key Record Dates
Results First Posted: April 28, 2022
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniel Podzamczer, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia:
Doravirine
Additional relevant MeSH terms:
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Emtricitabine tenofovir alafenamide
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents