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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
Gilead Sciences
Information provided by (Responsible Party):
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00120367
First received: July 11, 2005
Last updated: December 21, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Leukoencephalopathy, Progressive Multifocal
HIV Infections
Drug: Enfuvirtide
Drug: Tenofovir-Emtricitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

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

Estimated Enrollment: 30
Study Start Date: April 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00120367

Locations
France
Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre
Le Kremlin Bicetre, France, 94270
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Hoffmann-La Roche
Gilead Sciences
Investigators
Principal Investigator: Jacques Gasnault, MD Hopital Bicetre Kremlin Bicetre France
Study Chair: Dominique Costagliola Inserm U720
  More Information

No publications provided by French National Agency for Research on AIDS and Viral Hepatitis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00120367     History of Changes
Other Study ID Numbers: 2005-000424-16, ANRS 125
Study First Received: July 11, 2005
Last Updated: December 21, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
Leukoencephalopathy, Progressive Multifocal
HIV infections
HIV Fusion Inhibitors

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Leukoencephalopathy, Progressive Multifocal
Leukoencephalopathies
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Polyomavirus Infections
DNA Virus Infections
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Demyelinating Diseases
Enfuvirtide
HIV Fusion Inhibitors
Tenofovir
Emtricitabine
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 09, 2014