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Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125)

Primary Purpose

Leukoencephalopathy, Progressive Multifocal, HIV Infections

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Enfuvirtide
Tenofovir-Emtricitabine
Sponsored by
French National Agency for Research on AIDS and Viral Hepatitis
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukoencephalopathy, Progressive Multifocal focused on measuring Leukoencephalopathy, Progressive Multifocal, HIV infections, HIV Fusion Inhibitors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 18 years of age and older Have confirmed laboratory diagnosis of HIV infection Presenting with a clinical history of active PML evolving (or continuing to deteriorate) for less than 90 days Diagnosis of PML documented for less than 30 days at the inclusion by cerebral imaging (MRI) AND the absence of another demonstrated etiology AND the detection of JCV DNA in the CSF by qualitative PCR. Signed written inform consent Exclusion Criteria: Concomitant opportunistic infection of the central nervous system Pregnancy, breast-feeding Co-infection by the HIV2 History of immunotherapy including interleukin-2 and alpha-interferon History of treatment by FUZEON® or by cidofovir Contra-indication to receive FUZEON

Sites / Locations

  • Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre

Outcomes

Primary Outcome Measures

Estimation by the method of Kaplan-Meier of the rate of survival at M12

Secondary Outcome Measures

Rate of survival and functional score (Modified Rankin Outcome Scale) at M12
Evolution of the JC viral load in the CSF and percentage of patients with JC virus clearance of the CSF to M3 and M6
Evolution of the CD4 and CD8 T cells sub-populations and of the antivirus JC specific T cell responses at M12
Dosage of the concentration of enfuvirtide in the CSF

Full Information

First Posted
July 11, 2005
Last Updated
December 21, 2011
Sponsor
French National Agency for Research on AIDS and Viral Hepatitis
Collaborators
Hoffmann-La Roche, Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00120367
Brief Title
Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125)
Official Title
Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
April 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
French National Agency for Research on AIDS and Viral Hepatitis
Collaborators
Hoffmann-La Roche, Gilead Sciences

4. Oversight

5. Study Description

Brief Summary
Progressive multifocal leucoencephalopathy (PML) is a rare infectious disease of the brain, provoked by the JC virus. It usually occurs in subjects with impaired immune system as during HIV infection. To date, there is no specific antiviral treatment susceptible to cure PML. But it was shown in the setting of HIV-related PML, that combination antiretroviral therapy allows a restoration of the immune system and then might stop the progression of PML. The objective of this study is to appreciate the supplementary efficiency brought by an association of more powerful antiretroviral molecules including enfuvirtide on the evolution of PML. This research program will involve 30 patients in several centres in France. All the patients who will participate will receive enfuvirtide during 6 months in association with a combination of two or more potent antiretroviral drugs. The total duration of follow-up for a patient will be of 1 year.
Detailed Description
The aim of this open-label multicentre study is to estimate the effect of an early therapy intensification based on potent antiretroviral combination including enfuvirtide(FUZEON®) on survival in patients with HIV-1-related progressive multifocal leucoencephalopathy (PML). To demonstrate that the observed rate is significantly superior to 45%, the inclusion of 24 patients is necessary. At last, 30 patients will be recruited towards the risk estimated at 25% of invalid inclusion. Patients will be included on the following criteria : HIV-1 documented by Western Blot, clinical and radiological (MRI) evidence of active LEMP with clinical evolution (or deterioration) for less than 90 days, documentation of PML diagnosis for less than 30 days at the inclusion, informed consent (patient or confidence surrogate if decision making incapacity). Exclusion criteria will be the following: age less than 18-year-old ; concomitant opportunistic infection of the central nervous system; pregnancy - feeding; co-infection by the HIV2; history of immunotherapy (interleukin 2, alpha-interferon) or of treatment by FUZEON®; history of treatment by cidofovir; contra-indication to receive FUZEON ®. An independent committee will meet regularly to estimate the validity of PML diagnosis in included patients. The duration of the treatment by FUZEON® is 6 months in association with a combination of two or more antiretroviral molecules which will be pursued during the next 6 months. These molecules will be chosen according to the past treatment of the patients. A combination including efavirenz, lopinavir/ritonavir, and tenofovir/emtricitabine (under the shape of TRUVADA®) will be proposed to the naïve patients. For the pretreated patient(approximately a quarter of the inclusions), antiretroviral therapy will be chosen in every case on the basis of the therapeutic history and of the viral genotypes of resistance. Such association will contain at least two antiretroviral molecules, issued from two different families among the three following ones (nucleoside inhibitors of the reverse transcriptase, non-nucleoside inhibitors of the reverse transcriptase, protease inhibitors). The projected duration of the period of inclusion will be 18 months. A total duration of 2.5 years is projected. Evaluation criteria of the ANRS 125 trial are the following. Clinical: rate of survival and functional score (Modified Rankin Outcome Scale) to M12. Virological: evolution of the JC viral load in the CSF ; and percentage of patients with JC virus clearance of the CSF to M3 and M6. Immunological: evolution of T CD4 and T CD8 subpopulations. Evolution of the anti-JC virus specific T cell (CD4 and CD8) responses. Pharmacological: dosage of the concentration of enfuvirtide in the CSF compared with the plasma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukoencephalopathy, Progressive Multifocal, HIV Infections
Keywords
Leukoencephalopathy, Progressive Multifocal, HIV infections, HIV Fusion Inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Enfuvirtide
Intervention Type
Drug
Intervention Name(s)
Tenofovir-Emtricitabine
Primary Outcome Measure Information:
Title
Estimation by the method of Kaplan-Meier of the rate of survival at M12
Secondary Outcome Measure Information:
Title
Rate of survival and functional score (Modified Rankin Outcome Scale) at M12
Title
Evolution of the JC viral load in the CSF and percentage of patients with JC virus clearance of the CSF to M3 and M6
Title
Evolution of the CD4 and CD8 T cells sub-populations and of the antivirus JC specific T cell responses at M12
Title
Dosage of the concentration of enfuvirtide in the CSF

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age and older Have confirmed laboratory diagnosis of HIV infection Presenting with a clinical history of active PML evolving (or continuing to deteriorate) for less than 90 days Diagnosis of PML documented for less than 30 days at the inclusion by cerebral imaging (MRI) AND the absence of another demonstrated etiology AND the detection of JCV DNA in the CSF by qualitative PCR. Signed written inform consent Exclusion Criteria: Concomitant opportunistic infection of the central nervous system Pregnancy, breast-feeding Co-infection by the HIV2 History of immunotherapy including interleukin-2 and alpha-interferon History of treatment by FUZEON® or by cidofovir Contra-indication to receive FUZEON
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques Gasnault, MD
Organizational Affiliation
Hopital Bicetre Kremlin Bicetre France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dominique Costagliola
Organizational Affiliation
Inserm U720
Official's Role
Study Chair
Facility Information:
Facility Name
Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre
City
Le Kremlin Bicetre
ZIP/Postal Code
94270
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
21738597
Citation
Gasnault J, Costagliola D, Hendel-Chavez H, Dulioust A, Pakianather S, Mazet AA, de Goer de Herve MG, Lancar R, Lascaux AS, Porte L, Delfraissy JF, Taoufik Y; ANRS 125 Trial Team. Improved survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy receiving early 5-drug combination antiretroviral therapy. PLoS One. 2011;6(6):e20967. doi: 10.1371/journal.pone.0020967. Epub 2011 Jun 30.
Results Reference
derived

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Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125)

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