Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV Patients With Undetectable Viral Load (EASIER)

November 6, 2012 updated by: French National Agency for Research on AIDS and Viral Hepatitis

Randomized Non-inferiority Study Comparing a Strategy Maintaining Current Enfuvirtide-based Antiretroviral Therapy to a Strategy Replacing Enfuvirtide by an Integrase Inhibitor (Raltegravir) in HIV-1 Infected Subjects With Plasma Hiv-1 RNA Levels Below 400 Copies Per ml.ANRS 138 EASIER

Switching from enfuvirtide to raltegravir in the treatment of HIV-infected patients who sustain viral suppression with a combination therapy including enfuvirtide (or : with an enfuvirtide-based combination therapy)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In patients who have failed under the three main classes of antiretroviral agents (NRTI, NNRTI and PI) and in whom the control of viral replication in the plasma has ultimately been achieved with enfuvirtide, the aim is to sustain this virological success for as long as possible to thus enable satisfactory immune reconstitution, avoid further accumulation of viral mutations conferring resistance to the drugs and protect the patient from the risk of opportunistic disease and death.

Indeed, enfuvirtide is the lead compound in the new class of antiretroviral drugs which inhibit the fusion of HIV-1 virus with its target cell. Its in vivo efficacy was demonstrated during the pivotal studies TORO 1 and 2. Despite its efficacy, maintaining long-term treatment with enfuvirtide is nonetheless difficult for patients because of the constraints related to twice-daily subcutaneous parenteral injections. Furthermore, these subcutaneous injections are associated with inflammatory reactions at the injection site in 98 per cent of patients, without any reduction in frequency or severity over time. It is thus critical for patients who are well controlled by enfuvirtide to be able to simplify their treatment by replacing enfuvirtide with another active compound taken by mouth, which would enable maintenance of the virological response and acceptable safety in patients who have usually failed under the three main classes of antiretroviral drugs. A new antiviral compound, viral integrase inhibitor called raltegravir, could be proposed instead of enfuvirtide.

Study Type

Interventional

Enrollment (Actual)

170

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75010
        • Service des maladies infectieuses et tropicales Hopital Saint Louis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic HIV-1 infection
  • Treatment with a well-tolerated combination of antiretroviral drugs unchanged for at least 3 months, including enfuvirtide
  • Absence of any uncontrolled opportunistic disease
  • No restrictions on CD4 lymphocyte levels
  • Plasma HIV-1 RNA below 400 copies per ml for at least 3 months (at least two consecutive tests below 400 copies per ml prior to inclusion in the study, not including that on W -4)
  • For women of childbearing age, use of mechanical contraception during any sexual intercourse and negative pregnancy test (plasma ß HCG) at W -4

Exclusion Criteria:

  • HIV-2 infection
  • Plasma HIV-1 RNA levels above 400 copies/ml on one occasion during the 3 months prior to screening (or the pre-inclusion visit at W -4)
  • Poor compliance with antiretroviral therapy current at W -4
  • Current treatment with an investigational drug (except cohort ATU)
  • Patient previously treated with an integrase inhibitor in the context of a clinical study
  • Woman who is pregnant or likely to become so, is breastfeeding or refuses to use contraception
  • Multiple drug therapy ongoing or necessary in the foreseeable future for Kaposi's disease or lymphoma
  • Treatment with interferon ongoing or necessary in the foreseeable future for chronic hepatitis B or C
  • Acute hepatitis whatever the case, or decompensated cirrhosis
  • Current treatment with interferon, interleukin or anti-HIV vaccine
  • Any condition (including, but not limited to, the consumption of alcohol or drugs) which might, in the investigator's opinion, compromise the safety of treatment and/or patient compliance with the protocol
  • Significant biological abnormalities (hemoglobin below 8g per dl, polynuclear neutrophils below 750 per mm3, platelets below 50,000 per mm3, serum creatinine above 3 times the level deemed normal by the laboratory (N), ASAT or ALAT above 5N, serum lipase above 2N) and total bilirubin above 2N (except if the patient is receiving atazanavir or indinavir)

  • Concomitant treatments including one or more compounds interacting with UGT1A1

    • anti-infective agents: rifampicin/rifampin
    • psychotropic/anti-epileptic drugs: phenytoin, phenobarbital.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intensification arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir + enfuvirtide
Drug: FTC/TDF + EFV or LPV/R +T20
emtricitabine 200mg/TDF 300mg (1 pill per day) + efavirenz 600mg (1 pill per day) or lopinavir/ritonavir (3 pills twice a day) + enfuvirtide 90mg twice a day
Active Comparator: Standard arm
emtricitabine/TDF + efavirenz or lopinavir/ritonavir
Drug: FTC/TDF + EFV or LPV/R
emtricitabine 200mg/TDF 300mg (1 pill per day) + efavirenz 600mg (1 pill per day) or lopinavir/ritonavir (3 pills twice a day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
comparison of the proportions of virologic failure, defined as two consecutive pVL above 400 cp per ml, through 24 weeks in enfuvirtide-maintained arm versus raltegravir arm
Time Frame: W24
W24

Secondary Outcome Measures

Outcome Measure
Time Frame
comparison of time to onset of virologic failure
Time Frame: W24 and W48
W24 and W48
proportions of pts with pVL under 50 and 400 cp per ml respectively at week 24 and week 48 ;
Time Frame: W24 & W48
W24 & W48
plasma viral mutations in the event of virologic failure, compared to HIV-DNA archived mutations at baseline;
Time Frame: virologic failure
virologic failure
change in CD4 levels
Time Frame: between W0 and W48
between W0 and W48
incidence of HIV-related events
Time Frame: between W0 and W48
between W0 and W48
drug plasma and male genital tract pharmacokinetics;
Time Frame: W24 & W48
W24 & W48
incidence and type of adverse events, including adverse reactions
Time Frame: between W0 & W48
between W0 & W48
proportions of discontinuing allocated treatment strategy
Time Frame: between W0 & W48
between W0 & W48
quality of life and adherence
Time Frame: W4, W12, W24 and W48
W4, W12, W24 and W48
morphological and metabolic disorders outcome
Time Frame: between W0 & W48
between W0 & W48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Nathalie De Castro, MD, AP-HP Hopital saint Louis Paris
  • Principal Investigator: Jean M Molina, MD, AP-HP Hopital saint Louis Paris
  • Study Chair: Jean P Aboulker, MD, INSERM SC10 VILLEJUIF FRANCE

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

March 29, 2007

First Submitted That Met QC Criteria

March 29, 2007

First Posted (Estimate)

March 30, 2007

Study Record Updates

Last Update Posted (Estimate)

November 7, 2012

Last Update Submitted That Met QC Criteria

November 6, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2007-000162-20
  • ANRS 138 EASIER

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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