Roche trials database

Protocol number:

ML17819

Title of Study:

An open-label study to assess the safety and tolerability of Fuzeon in combination with a free choice of antiviral regimen in Thai patients with advanced HIV infection.

Sponsor:

F Hoffman-La Roche Ltd

Company division:

Pharmaceutical

Product name:

enfuvirtide

Generic name:

enfuvirtide

Therapeutic area:

• HIV Infections

Clinical study summary:

This open-label study was designed to assess the safety and tolerability of Fuzeon (enfuvirtide) in combination with antiviral regimen in patients with advanced HIV-1 infection. Patient who failed to respond to previous antiretroviral therapies (protease inhibitors, nucleoside reverse transcriptase inhibitors or non-nucleoside transcriptase inhibitors) were eligible to participate in this study.

Study center(s):

5 centers in Thailand

Phase of development:

IV

Objectives:

The objective was to assess the safety and tolerability of Fuzeon in patients with advanced HIV-1 disease.

Methodology:

The study was conducted in 5 centers in Thailand. Eligible patients received Fuzeon twice a day for 96 weeks. Physical examination, routine chemistry, hematology testing and adverse events were assessed at every clinic visit at weeks 2, 4, 8, 12 and every 12 weeks thereafter until the end of treatment. Frequency and timing of CD4 cell counts and HIV RNA viral load testing were done according to each center’s clinic practice. Extra visits due to any adverse events were also recorded.

Number of patients (planned/analyzed):

30 patients planned; 23 patients analyzed

Diagnosis and main criteria for inclusion:

Patients over the age of 16 years, with HIV-1 infection, who were for at least 6 months on antiretroviral treatment of protease inhibitors, nucleoside reverse transcriptase inhibitors or non-nucleoside reverse transcriptase inhibitors and who had developed genotypic or phenotypic resistance and/or treatment-limiting toxicity on the treatment regimen.

Test product, dose and mode of administration or test procedure:

Enfuvirtide 90 mg was administered as subcutaneous injection twice a day.

Duration of treatment:

96 weeks

Reference therapy, dose and mode of administration or reference procedure:

N/A

Criteria for evaluation (efficacy, safety):

Safety

Adverse events; serious adverse events; AIDS defining events; discontinuation of treatment; laboratory test results

Statistical methods:

Only descriptive statistics of safety data (discontinuations, serious adverse events, and serious AIDS defining events) were reported from this study. For the purpose of reporting, the analysis population was defined as the number of patients who enrolled in the study and received at least one dose of Fuzeon.

Summary (efficacy, safety, other results):

Baseline Characteristics

Twenty three patients were enrolled to the study from February 2004 to December 2006; 17 patients completed the 96 weeks of treatment and 6 patients did not complete the study. Nineteen patients were male and four were female with a mean age of 42.2 years (SD=8.6). The HIV RNA level was less than 75,000 copies/ml (9 patients), between 75,000-100,000 copies/ml (10 patients) or more than 100,000 copies/ml (4 patients). In 17 patients, the level of CD4 cell count was less than 50 cells/mm³.

All patients had been previously treated with various nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) and had antiviral drug-resistant HIV strains. All patients had been treated with NRTIs and PIs, whereas 21 patients had been treated with all 3 classes of antiviral drugs. The number of antiviral drugs with which the patients were treated ranged from 3-7 NRTIs, 1-2 NNRTIs and 1-6 PIs. Stavudine was the most frequently used NRTI, efavirenz and nevirapine were the most frequently used NNRTIs and indinavir was the most frequently used PI.

AIDS defining events

AIDS defining events were classified into 6 groups: Parasitic infections, viral infections, fungal infections, bacterial infections, neoplastic disease, and others. There were 33 AIDS defining events reported from 23 patient. The most common opportunistic infection was tuberculosis (13 events), followed by cryptococcal infections, Pneumocystis jirovicii pneumonia, cytomegalovirus retinitis, and Mycobacterium avium complex infections (5, 5, 3, and 3 events, respectively). Neoplastic disease was not reported.

Adverse events

A total of 126 adverse events were reported from 23 patients. The most common adverse events were injection site reactions: indurations, pain, swelling, rash and bleeding at injection sites, development of nodules and/or inflammatory nodules, diarrhea and upper respiratory tract infections. The injection site adverse events were well tolerated by 22 patients. There were 11 serious adverse events reported from 6 patients. These events were related to HIV disease and its complications, and included severe anemia, cellulites, skin infections, acute pancreatitis, acute diarrhea, acute severe abdominal pain, acute colitis, immune reconstitution inflammatory syndrome, bronchiectasis, brain mass and brainstem stroke. Of the 6 patients who did not complete the study, 3 patients expired, 2 patients withdrew consent due to personal reasons and 1 patient withdrew due to injection site adverse event.

Conclusions:

The treatment of drug-resistant HIV-1 infected patients with relatively low CD4 cell counts with Fuzeon in addition to other common antiretroviral therapy was well tolerated. The incidence of adverse events did not compromise the patient compliance to the therapy.

Date of report:

01.07.2010

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