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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier:
NCT00454337
First received: March 29, 2007
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

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)


Condition Intervention Phase
HIV Infections
Drug: FTC/TDF + EFV or LPV/R +T20
Drug: FTC/TDF + EFV or LPV/R
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • comparison of time to onset of virologic failure [ Time Frame: W24 and W48 ] [ Designated as safety issue: No ]
  • proportions of pts with pVL under 50 and 400 cp per ml respectively at week 24 and week 48 ; [ Time Frame: W24 & W48 ] [ Designated as safety issue: No ]
  • plasma viral mutations in the event of virologic failure, compared to HIV-DNA archived mutations at baseline; [ Time Frame: virologic failure ] [ Designated as safety issue: Yes ]
  • change in CD4 levels [ Time Frame: between W0 and W48 ] [ Designated as safety issue: No ]
  • incidence of HIV-related events [ Time Frame: between W0 and W48 ] [ Designated as safety issue: Yes ]
  • drug plasma and male genital tract pharmacokinetics; [ Time Frame: W24 & W48 ] [ Designated as safety issue: No ]
  • incidence and type of adverse events, including adverse reactions [ Time Frame: between W0 & W48 ] [ Designated as safety issue: Yes ]
  • proportions of discontinuing allocated treatment strategy [ Time Frame: between W0 & W48 ] [ Designated as safety issue: Yes ]
  • quality of life and adherence [ Time Frame: W4, W12, W24 and W48 ] [ Designated as safety issue: No ]
  • morphological and metabolic disorders outcome [ Time Frame: between W0 & W48 ] [ Designated as safety issue: No ]

Enrollment: 170
Study Start Date: May 2007
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454337

Locations
France
Service des maladies infectieuses et tropicales Hopital Saint Louis
Paris, France, 75010
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Merck Sharp & Dohme Corp.
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
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier: NCT00454337     History of Changes
Other Study ID Numbers: 2007-000162-20, ANRS 138 EASIER
Study First Received: March 29, 2007
Last Updated: November 6, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV-1 infection
enfuvirtide
raltegravir
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Enfuvirtide
Lopinavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Fusion Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014