HIV InfectionPhase 3ENCORE1-CNSNCT01451333
The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
A Phase 3 study testing Efavirenz in people with HIV Infection, run by Kirby Institute at 5 sites in 3 countries.
Trial summary
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Efavirenz
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Sep 2011to Feb 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
Who cannot join
- Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
- CNS opportunistic infections in the past 12 weeks of randomisation
- Bacterial or viral meningitis in the past 12 weeks of randomisation
- Head injury requiring medical assessment in the past 12 weeks of randomisation
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Thailand2 sites
Khon Kaen University
Khon Kaen, Changwat Khon Kaen, 40002
HIVNAT Research Collaboration
Patumwan, Bangkok, 10330
United Kingdom2 sites
Imperial College, St. Mary's Hospital
Clinical Trials Centre, Winston Churchil Wing, London, W2 1NY
Chelsea and Westminster Hospital
Hiv/gum Laboratory 5th Floor Saint Stephen Centre, London, SW10 9NH
About this study
Official title: The EFV Central Nervous System Exposure Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.
- Conditions
- HIV Infection
- Being tested
- Efavirenz
- Keywords
- HIV, Efavirenz, Central Nervous System (CNS), Lumbar puncture, Dose reduction
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EfavirenzDrug
600mg qd; 3 x 200mg qd
EfavirenzDrug
400mg qd; 2 x 200mg
| Study group | Role | What they receive |
|---|---|---|
| Reduced dose Efavirenz arm | Experimental | Patient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd). Receives: Drug: Efavirenz |
| Normal Efavirenz dose arm | Active comparator | Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd) Receives: Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
comparison of mean CSF concentration of EFV from both doses after week 24.
measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
Measured: 24 weeks
Secondary outcomes (8)
CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis
The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.
Measured: 24 weeks
The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments
Measured: 24 weeks
The relationship between CSF EFV exposure and other study parameters such as race and sex.
Measured: 24 weeks
The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)
Measured: 24 weeks
CSF HIV RNA measurement after 12 - 24 weeks of study therapy
Measured: 24 weeks
Relationship between plasma HIV RNA and CSF HIV RNA
Measured: 24 weeks
CSF biomarker analysis after 12 - 24 weeks of study therapy
Measured: 24 weeks
comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2011 (estimated)
- Study startSep 2011
- Primary completionOct 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Collaborators
- Imperial College London
- Responsible party
- Sponsor
- Investigators
- Alan Winston, Dr., Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451333
- Sponsor's protocol ID
- NCHECR-ENCORE1-CNS
- Acronym
- ENCORE1-CNS
- Status last verified
- May 2013
- First submitted
- 5 Jan 2011
- Last updated
- 13 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The EFV Central Nervous System Exposure Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks
- ClinicalTrials.gov ID
- NCT01451333
- Acronym / sponsor ID
- ENCORE1-CNS / NCHECR-ENCORE1-CNS
- Conditions
- HIV Infection
- Keywords
- HIV, Efavirenz, Central Nervous System (CNS), Lumbar puncture, Dose reduction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Collaborators
- Imperial College London
- Study start
- Sep 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 13 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reduced dose Efavirenz arm | Experimental | Drug: EfavirenzPatient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd). |
| Normal Efavirenz dose arm | Active comparator | Drug: EfavirenzPatient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
Key exclusion criteria (4 listed)
- Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
- CNS opportunistic infections in the past 12 weeks of randomisation
- Bacterial or viral meningitis in the past 12 weeks of randomisation
- Head injury requiring medical assessment in the past 12 weeks of randomisation
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 |
|---|---|---|
| Efavirenz600mg qd; 3 x 200mg qd | Drug | Normal Efavirenz dose arm |
| Efavirenz400mg qd; 2 x 200mg | Drug | Reduced dose Efavirenz arm |
Primary outcome
comparison of mean CSF concentration of EFV from both doses after week 24.
Time frame: 24 weeks
measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
8 secondary outcomes
CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis
Time frame: 24 weeks
The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments
Time frame: 24 weeks
The relationship between CSF EFV exposure and other study parameters such as race and sex.
Time frame: 24 weeks
The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)
Time frame: 24 weeks
CSF HIV RNA measurement after 12 - 24 weeks of study therapy
Time frame: 24 weeks
Relationship between plasma HIV RNA and CSF HIV RNA
Time frame: 24 weeks
CSF biomarker analysis after 12 - 24 weeks of study therapy
Time frame: 24 weeks
comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2013.
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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.
Alan Winston, Dr. principal investigator
Imperial College London
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Efavirenz in people with HIV Infection, run by Kirby Institute at 5 sites in 3 countries.
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 1 inclusion and 4 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 13 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Thailand, United Kingdom, Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
comparison of mean CSF concentration of EFV from both doses after week 24. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 May 2013.