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HIV InfectionPhase 2SENSENCT00903682

A Clinical Trial Comparing the Tolerability of Etravirine to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Treatment-naive HIV-1 Infected Patients

A Phase 2 study testing etravirine (ETR, TMC125) and efavirenz (EFV) in people with HIV Infection and HIV, run by Janssen-Cilag International NV at 33 sites in 11 countries.

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

The purpose of this study is to compare the neuropsychiatric adverse event profiles of etravirine 400mg once daily versus efavirenz 600mg once daily, in combination with 2 N(t)RTIs, in approximately 150 treatment-naÃ-ve HIV-1 infected patients. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
etravirine (ETR, TMC125) and efavirenz (EFV)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
157 participants
Where
33 sitesin 11 countries
Study dates
Jun 2009to Jan 2011
Phase
Phase 2
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented HIV-1 infection
  • In the judgement of the investigator, it is appropriate to initiate ARV therapy based on the patients medical condition and taking into account applicable guidelines for the treatment of HIV-1 infection
  • Patient has access to an investigator-selected ARV regimen post-study in accordance with applicable guidelines for the treatment of HIV-1 infection
  • HIV-1 plasma viral load at screening >= 5000 HIV-1 RNA (copies/ml)
  • Predicted phenotypic sensitivity to the currently approved NNRTIs and to the N(t)RTIs in their background regimen at screening

Who cannot join

  • Any previous treatment with a therapeutic HIV vaccine or use of ARVs, including use of NVP for the prevention of vertical HIV transmission
  • The presence of at least one of the mutations that are specific indicators of transmitted (or primary) drug resistance
  • Known infection with HIV-2 or with HIV-1 group O
  • Category C AIDS defining illness, except stable Kaposi's Sarcoma, wasting syndrome if not progressive
  • Pneumocystis jiroveci/carinii Pneumonia (PCP) that is considered not cured
  • Specific grade 3 or 4 laboratory abnormalities

Trial locations and contacts

33 sites in 11 countries.

33 sites in 11 countries

Germany7 sites

  • Study site

    Berlin

  • Study site

    Bonn

  • Study site

    Cologne

  • Study site

    Essen

  • Study site

    Frankfurt

  • Study site

    Hamburg

  • Study site

    Hanover

Other trials in Germany

France5 sites

  • Study site

    Bordeaux

  • Study site

    Lyon

  • Study site

    Nice

  • Study site

    Paris

  • Study site

    Strasbourg

Other trials in France

Israel4 sites

  • Study site

    Haifa

  • Study site

    Jerusalem

  • Study site

    Ramat Gan

  • Study site

    Tel Aviv

Other trials in Israel

Spain4 sites

  • Study site

    Barcelona

  • Study site

    Granada

  • Study site

    Madrid

  • Study site

    Vigo

Other trials in Spain

Austria2 sites

  • Study site

    Salzburg

  • Study site

    Vienna

Other trials in Austria

Denmark2 sites

  • Study site

    Aarhus

  • Study site

    Odense

Other trials in Denmark

Romania2 sites

  • Study site

    Bucharest

  • Study site

    Constanța

Other trials in Romania

Russia2 sites

  • Study site

    Moscow

  • Study site

    Saint Petersburg

Other trials in Russia

Switzerland2 sites

  • Study site

    Bern

  • Study site

    Zurich

Other trials in Switzerland

United Kingdom2 sites

  • Study site

    Brighton

  • Study site

    London

Other trials in United Kingdom

Hungary1 site

  • Study site

    Budapest

Other trials in Hungary

About this study

Official title: A Phase IIb, Multi-centre, Randomised, Double-blind, Active-controlled Trial Comparing the Neuropsychiatric Adverse Event Profile of Etravirine 400mg qd Versus Efavirenz 600mg qd in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in ARV Therapy-naive HIV-1 Infected Subjects

The purpose of this study is to compare the neuropsychiatric adverse event profiles of etravirine 400mg once daily versus efavirenz 600mg once daily, in combination with 2 N(t)RTIs, in approximately 150 treatment-naÃ-ve HIV-1 infected patients. Safety, tolerability and efficacy of both treatment arms will be assessed throughout the study.

Read the detailed description

This is a phase IIb, randomised (study medication is assigned by chance), double-blind (neither the patient nor the study physician will know to which treatment group the patient is assigned) trial to assess the neuropsychiatric adverse event profile of etravirine (ETR) 400mg once daily versus efavirenz (EFV) 600mg once daily, each in combination with an investigator-selected background of 2 other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs). The combination of N[t]RTIs to be chosen by the study physician can be abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/lamivudine (3TC) or tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC). Approximately 150 Human Immuno-deficiency Virus type 1 (HIV-1) infected patients, who have never received any antiretroviral (ARV) treatment will be randomly assigned (like tossing a coin) to either the etravirine treatment group or the control group (efavirenz). The study period includes a screening period of maximum 6 weeks, a 48 week treatment period, an additional 2-8 weeks treatment until unblinding (study physician (and patient) will receive information to which treatment group the patient is assigned), followed by a 4 weeks follow-up period. The main purpose of this study is to gather further data on how many, how often, and how severe the central nervous system and psychiatric (neuropsychiatric) events are between the two treatment groups. In addition, the study will look at overall safety, tolerability and antiviral effectiveness between the two treatment groups. During the trial, patients' health will be monitored by physical examination, checking of vital signs (blood pressure / pulse), and laboratory testing on blood and urine samples. Also blood samples will be drawn to measure the antiviral effectiveness (i.e., decrease of the plasma viral load to a level <50 HIV-1 RNA (ribonucleic acid) copies/mL), immunology assessments (to assess the body's immune system) and pharmacokinetic (to measure the drug level in blood) analysis of etravirine. Patients will be asked to complete the "HIV Patient Symptoms Profile" (HIV PSP) Questionnaire at each visit, which contains questions relating to the impact on patients' current health and well-being. The study hypothesis is that the proportion of patients with at least one neuropsychiatric adverse event related to the study drug, observed between start of treatment (Baseline; BSL) through Week 12, is significantly lower in the etravirine group than in the efavirenz group. Patients will be taking blinded medication twice a day, administered orally (by mouth). Only one of the blinded doses will contain an active ingredient. Etravirine 400mg (or dummy-pills) - 4 tablets - should be taken once a day, following a meal, preferably breakfast. Efavirenz 600mg (or dummy-pill) - 1 tablet - should be administered once daily on an empty stomach, preferably at bedtime.The intake of the investigator-selected N[t]RTIs should be taken as instructed by the investigator.

Being tested
etravirine (ETR, TMC125), efavirenz (EFV)
Keywords
HIV, Intelence, etravirine, ETR, TMC125, Sustiva, efavirenz, EFV, Non-nucleoside Reverse Transcriptase Inhibitor, NNRTI, treatment-naive
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome

What participants receive

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

  • etravirine (ETR, TMC125)Drug

    400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks

  • efavirenz (EFV)Drug

    600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks

Study groups in NCT00903682
Study groupRoleWhat they receive
etravirineExperimentaletravirine (ETR TMC125) 400mg once daily (4x100mg tablet) + 2 NRTI + 1 EFV placebo tablet for 48 weeks
Receives: Drug: etravirine (ETR, TMC125)
efavirenzActive comparatorefavirenz (EFV) 600mg once daily (1x600mg tablet) + 2 NRTIs + 4 ETR placebo tablets for 48 weeks
Receives: Drug: efavirenz (EFV)

What is being measured

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

  1. Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event

    Proportion of patients with at least 1 treatment-emergent Grade 1-4 Central Nervous System or psychiatric Adverse Event, observed between Baseline through Week 12 and judged by investigator to be at least possibly related to the study drug in ETR group versus EFV group. All Adverse Events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events ("DAIDS AE grading table"). Grade 1-4 covers all severities.

    Measured: between baseline and 12 weeks

Secondary outcomes (6)

  1. Antiviral Activity of ETR vs. EFV

    The proportion of patients with confirmed plasma viral load <50 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)

    Measured: between baseline and week 48

  2. Antiviral Activity of ETR vs. EFV

    The proportion of patients with confirmed plasma viral load <200 copies/mL at Week 48 as assessed by Time to Loss of Virologic Response (TLOVR)

    Measured: between baseline and week 48

  3. Mean Change From Baseline in Neuropsychiatric and Total Tolerabililty Score

    The HIV Patient Symptoms Profile measures the tolerability of HIV treatment from the patient's perspective, using 14 concept scales in maximum 84 questions. The response options include a "no" or "yes" answer to "Did symptom occur?". If "yes", there is a problem scale which ranges from 1 = "I had this symptom and it was not a problem" to 5 = "I had this symptom and it was a severe problem". A neuropsychiatric tolerability score is composed as the sum of 21 items and ranges from 0 (best) to 105 (worse). A total Tolerability score (ie, the sum of all items) ranges from 0 (best) to 420 (worse)

    Measured: between baseline and week 48

  4. Neuropsychiatric Adverse Events by Week 48

    The percentage of patients with at least 1 treatment emergent Grade 1 -4 neurologic or psychiatric adverse event, judged by the investigator to be at least possibly related to the study drug.

    Measured: from baseline to week 48

  5. Mean Change From Baseline in CD4+ Cell Count

    The mean change in CD4+ cell count from baseline was calculated with a last observation carried forward method; i.e. the last observed value was carried forward, irrespective of the reason for discontinuation.

    Measured: at baseline and week 2, 6, 12, 24, 36 and 48

  6. Resistance Determinations

    The evolution of viral genotype and phenotype was assessed by the number of patients with resistance-associated mutations emerging at the endpoint. A mutation was considered emerging if it was present at endpoint and not present at baseline or any pre-baseline assessment. (NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; RAM = resistance-associated mutation, IAS-USA = International AIDS Society - USA)

    Measured: at baseline and all subsequent visits until week 48 in case if virologic failure

Timeline

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

  1. First posted18 May 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionFeb 2010
  4. Study completionJan 2011

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
157 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00903682
Sponsor's protocol ID
CR015751
Other IDs
TMC125VIR2038, 2008-008655-42, 2008
Acronym
SENSE
Status last verified
Jan 2013
First submitted
14 May 2009
Last updated
14 Jan 2013
Data monitoring committee
Yes

Publications

  • Nelson M, Stellbrink HJ, Podzamczer D, Banhegyi D, Gazzard B, Hill A, van Delft Y, Vingerhoets J, Stark T, Marks S. A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. AIDS. 2011 Jan 28;25(3):335-40. doi: 10.1097/QAD.0b013e3283416873.

    PubMed 21150563

  • Gazzard B, Duvivier C, Zagler C, Castagna A, Hill A, van Delft Y, Marks S. Phase 2 double-blind, randomized trial of etravirine versus efavirenz in treatment-naive patients: 48-week results. AIDS. 2011 Nov 28;25(18):2249-58. doi: 10.1097/QAD.0b013e32834c4c06.

    PubMed 21881478

  • Fatkenheuer G, Duvivier C, Rieger A, Durant J, Rey D, Schmidt W, Hill A, van Delft Y, Marks S; SENSE Study Team. Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial. J Antimicrob Chemother. 2012 Mar;67(3):685-90. doi: 10.1093/jac/dkr533. Epub 2011 Dec 29.

    PubMed 22210755

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing etravirine (ETR, TMC125) and efavirenz (EFV) in people with HIV Infection and HIV, run by Janssen-Cilag International NV at 33 sites in 11 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 5 inclusion and 6 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 14 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Germany, France, Israel, Spain, Austria and 6 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 7 Mar 2011). 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?

Proportion of Patients With at Least 1 Treatment-emergent Grade 1-4 Central Nervous System or Psychiatric Adverse Event (time frame: between baseline and 12 weeks). 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 NCT00903682, which also lists 3 linked publications.

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 14 Jan 2013.

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