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

HIV Infections Clinical Trial

Official title:

Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00120367
• Other study ID #: 2005-000424-16
• Secondary ID: ANRS 125
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2005
• Last updated: December 21, 2011
• Start date: April 2005
• Est. completion date: December 2007

Study information

• Verified date: December 2011
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Infection
• Leukoencephalopathies
• Leukoencephalopathy, Progressive Multifocal

Intervention

Drug:
• Enfuvirtide

• Tenofovir-Emtricitabine

Locations

Country	Name	City	State
France	Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre	Le Kremlin Bicetre

Sponsors (3)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Gilead Sciences, Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimation by the method of Kaplan-Meier of the rate of survival at M12
Secondary	Rate of survival and functional score (Modified Rankin Outcome Scale) at M12
Secondary	Evolution of the JC viral load in the CSF and percentage of patients with JC virus clearance of the CSF to M3 and M6
Secondary	Evolution of the CD4 and CD8 T cells sub-populations and of the antivirus JC specific T cell responses at M12
Secondary	Dosage of the concentration of enfuvirtide in the CSF