Leukoencephalopathy, Progressive MultifocalPhase 2NCT00120367
Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125)
A Phase 2 study testing Enfuvirtide and Tenofovir-Emtricitabine in people with Leukoencephalopathy, Progressive Multifocal and HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukoencephalopathy, Progressive Multifocal, HIV Infections
- What is being tested?
- Enfuvirtide and Tenofovir-Emtricitabine
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2005to Dec 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Medecine interne et Maladies Infectieuses, Hopital Bicetre
Le Kremlin-Bicêtre, 94270
About this study
Official title: Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial
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.
Read the 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.
- Being tested
- Enfuvirtide, Tenofovir-Emtricitabine
- Keywords
- Leukoencephalopathy, Progressive Multifocal, HIV infections, HIV Fusion Inhibitors
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnfuvirtideDrug
Tenofovir-EmtricitabineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimation by the method of Kaplan-Meier of the rate of survival at M12
Secondary outcomes (4)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2005 (estimated)
- Study startApr 2005
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukoencephalopathy, Progressive MultifocalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Collaborators
- Hoffmann-La Roche, Gilead Sciences
- Responsible party
- Sponsor
- Investigators
- Jacques Gasnault, MD, Principal investigator, Hopital Bicetre Kremlin Bicetre FranceDominique Costagliola, Study chair, Inserm U720
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00120367
- Sponsor's protocol ID
- ANRS 125
- Other IDs
- 2005-000424-16, 2005
- Status last verified
- Dec 2011
- First submitted
- 11 Jul 2005
- Last updated
- 2 Apr 2026
- Results posted
- No
Publications
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.
PubMed 21738597
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Intensification of Combination Antiretroviral Therapy Including FUZEON® in the Treatment of Progressive Multifocal Leucoencephalopathy During HIV-1 Infection ANRS 125 Trial
- ClinicalTrials.gov ID
- NCT00120367
- Acronym / sponsor ID
- ANRS 125
- Keywords
- Leukoencephalopathy, Progressive Multifocal, HIV infections, HIV Fusion Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Collaborators
- Hoffmann-La Roche, Gilead Sciences
- Study start
- Apr 2005
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 18 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enfuvirtide | Drug | – |
| Tenofovir-Emtricitabine | Drug | – |
Primary outcome
Estimation by the method of Kaplan-Meier of the rate of survival at M12
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Derived from this study: PubMed 21738597Gasnault 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacques Gasnault, MD principal investigator
Hopital Bicetre Kremlin Bicetre France
Dominique Costagliola study chair
Inserm U720
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enfuvirtide and Tenofovir-Emtricitabine in people with Leukoencephalopathy, Progressive Multifocal and HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimation by the method of Kaplan-Meier of the rate of survival at M12. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00120367, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.