HIV-1-infectionPhase 3NCT04079452

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

A Phase 3 study testing Doravirine and Descovy in people with HIV-1-infection, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV-1-infection
What is being tested?: Doravirine and Descovy
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteSpain
Study dates: 18 Feb 2020to 31 Aug 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
Signed and dated written informed consent prior to inclusion.
Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.

Who cannot join

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

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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.

Trial locations and contacts

1 site in 1 country.

Spain1 site

Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907

Other trials in Spain

About this study

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.

Read the 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
Being tested: Doravirine, Descovy
Keywords: Doravirine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DoravirineDrug
Also called MK-1439
Doravirine 100 mg tablet
DescovyDrug
Also called TAF/FTC
Tenofovir alafenamide 25 mg / emtricitabine 200 mg tablet

Study groups in NCT04079452
Study group	Role	What they receive
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 Receives: Drug: Doravirine; Drug: Descovy

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Doravirine Concentrations in Cerebrospinal Fluid
Total Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF
Measured: 4 Weeks
Total Doravirine Concentrations in Blood Plasma
Total Doravirine concentrations in blood plasma
Measured: 4 Weeks
Total Doravirine Concentration CSF/Plasma Ratio
total Doravirine CSF/plasma ratio
Measured: 4 Weeks
HIV-1 RNA in Cerebrospinal Fluid
Number of patients with HIV-1 RNA cerebrospinal fluid <40 copies/ml
Measured: 4 Weeks
HIV-1 RNA in Blood Plasma
Number of patients with HIV-1 RNA in blood plasma <40 copies/ml
Measured: 4 Weeks
Unbound Doravirine Concentrations in CSF
Unbound Doravirine concentrations in cerebrospinal fluid in HIV-1 infected individual receiving ART with Doravirine+FTC/TAF
Measured: 4 Weeks
Doravirine Concentrations in Blood Plasma
Unbound Doravirine concentrations in blood plasma
Measured: 4 Weeks
Unbound Doravirine Concentration CSF/Plasma Ratio
Unbound Doravirine CSF/plasma ratio
Measured: 4 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Feb 202031 Aug 2020

First posted6 Sep 2019
Study start18 Feb 2020
Primary completion31 Aug 2020
Study completion31 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV-1-infectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04079452
Sponsor's protocol ID: DORACeNeS
Other IDs: 2018-003915-24, 2018
Status last verified: Apr 2022
First submitted: 3 Sep 2019
Last updated: 28 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
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Active, not recruitingPhase 2/3
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen (ARTISTRY-1)
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All HIV-1-infection trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Doravirine Concentrations and Antiviral Activity in Cerebrospinal Fluid in HIV-1 Infected Individuals
ClinicalTrials.gov ID: NCT04079452
Acronym / sponsor ID: DORACeNeS
Conditions: HIV-1-infection
Keywords: Doravirine
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
Collaborators: Institut d'Investigació Biomèdica de Bellvitge, Hospital Universitari de Bellvitge
Study start: 18 Feb 2020 (actual)
Primary completion: 31 Aug 2020 (actual)
Study completion: 31 Aug 2020 (actual)
First posted: 6 Sep 2019 (actual)
Results: Posted 28 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Doravirine + Descovy® TAF/FTC	Experimental	Drug: Doravirine, Drug: DescovyDoravirine (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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.
Signed and dated written informed consent prior to inclusion.
Subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse from the screening visit throughout the duration of the study.

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DoravirineAlso: MK-1439Doravirine 100 mg tablet	Drug	Doravirine + Descovy® TAF/FTC
DescovyAlso: TAF/FTCTenofovir alafenamide 25 mg / emtricitabine 200 mg tablet	Drug	Doravirine + Descovy® TAF/FTC

Primary outcome

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
Total Doravirine Concentrations in Blood Plasma
Time frame: 4 Weeks
Total Doravirine concentrations in blood plasma
Total Doravirine Concentration CSF/Plasma Ratio
Time frame: 4 Weeks
total Doravirine CSF/plasma ratio
HIV-1 RNA in Cerebrospinal Fluid
Time frame: 4 Weeks
Number of patients with HIV-1 RNA cerebrospinal fluid <40 copies/ml
HIV-1 RNA in Blood Plasma
Time frame: 4 Weeks
Number of patients with HIV-1 RNA in blood plasma <40 copies/ml
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
Doravirine Concentrations in Blood Plasma
Time frame: 4 Weeks
Unbound Doravirine concentrations in blood plasma
Unbound Doravirine Concentration CSF/Plasma Ratio
Time frame: 4 Weeks
Unbound Doravirine CSF/plasma ratio

Results and safety

Results posted to the registry on 28 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Doravirie+TAF/FTC Arm (Single Arm)	15	15

Primary outcome: Total Doravirine Concentrations in Cerebrospinal Fluid

Time frame: 4 Weeks. Median (Inter-Quartile Range). Unit: ng/ml

Measure	Doravirine+TAF/FTC Arm (Single Arm) n = 15
Value	58.6 (23.2 to 127.3)

Population analysed: Descriptive analysis was performed for all participants (15), defining median and IQR of Doravirine concentrations in CSF

Primary outcome: Total Doravirine Concentrations in Blood Plasma

Time frame: 4 Weeks. Median (Inter-Quartile Range). Unit: ng/ml

Measure	Doravirie+TAF/FTC Arm (Single Arm) n = 15
Value	417.6 (169.5 to 942.2)

Primary outcome: Total Doravirine Concentration CSF/Plasma Ratio

Time frame: 4 Weeks. Median (Inter-Quartile Range). Unit: ratio

Measure	Doravirine+TAF/FTC Arm (Single Arm) n = 15
Value	0.13 (0.09 to 0.19)

Primary outcome: HIV-1 RNA in Cerebrospinal Fluid

Time frame: 4 Weeks. Count of participants. Unit: Participants

Measure	Doravirine+TAF/FTC Arm (Single Arm) n = 15
Value	13

Adverse events

Time frame: 6 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Doravirine+TAF/FTC Arm (Single Arm)	0 of 15 (0%)	1 of 15 (6.7%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for HIV-1-infection

RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Daniel Podzamczer, PhD Chief principal investigator

Hospital Universitari de Bellvitge

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Total Doravirine Concentrations in Cerebrospinal Fluid (time frame: 4 Weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04079452.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2022.