This study will determine the safety and tolerability of Fuzeon (enfuvirtide) used together
with other treatments for HIV infection in patients with advanced HIV disease. Fuzeon is an
antiretroviral drug. Unlike other antiretrovirals, however, which work against the virus
once it is already in the cell, Fuzeon prevents the virus from getting into healthy cells.
Patients 18 years of age and older with advanced HIV-1 infection, who do not respond to
approved antiretroviral therapy, may be eligible for this study. Candidates must have a CD4
lymphocyte count less than 100 cells/mm3 and a viral load greater than 10,000 copies/mL.
They will be screened with a medical history, physical examination, and blood tests, and may
also have an electrocardiogram (ECG), chest x-ray and urine test.
Patients enrolled in the study will be re-examined and have additional blood tests before
beginning treatment with Fuzeon. They will then be taught how to self-inject the medicine
under the skin and will take two doses daily (less than 1/4 teaspoon each), 12 hours apart.
After the first treatment, participants will have follow-up visits at weeks 1, 2, 4, 8, 12,
24, 36, 48, and every 12 weeks after that, if necessary, until 12 weeks after the drug
becomes commercially available. Visits may be scheduled more often if a problem arises.
During the follow-up visits, patients will have blood drawn, and their blood pressure, pulse
rate and temperature will be checked. They will also report any drug side effects they have
Patients may continue to take Fuzeon as long as they benefit from therapy and do not
experience severe side effects from the treatment. The drug will be provided to
participants until 12 weeks after it is sold in the United States.
Over the last few years, an unprecedented decrease in the mortality and morbidity associated
with AIDS has been achieved attributed to the use of highly active antiretroviral therapy
(HAART) which consists of three different classes of drugs: Nucleoside reverse
transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and non-nucleoside reverse
transcriptase inhibitors (NNRTIs). However, the durability of viral suppression is often
limited by treatment with combinations of non-fully suppressive antiretroviral agents.
Heavily pretreated patients often possess multiple mutations of the reverse transcriptase
and protease genes resulting in multi-drug resistance. Thus, a pharmacological agent
effective at an alternate point in the virus replication cycle would make a valuable
addition to the anti-HIV armamentarium. T-20, enfuvirtide, is the first drug to be
developed which specifically inhibits the function of the gp41 transmembrane glycoprotein of
HIV-1. The objective of this study is to assess the safety and tolerability of Fuzeon
(Enfuvirtide) in patients who are limited by the current commercially available
antiretroviral agents or agents available via early access or compassionate use programs as
per the judgment of the investigator or patients with advanced disease and most in need of
therapy. This study is a multicenter, open-label, single-arm, safety study. Each patient
will receive enfuvirtide 90 mg (deliverable dose) via subcutaneous injection twice daily
with food, in combination additional antiretroviral agents. Subjects will continue to
receive enfuvirtide until 12 weeks after commercial availability of enfuvirtide in the
United States. Laboratory testing, CD4+lymphocyte counts, HIV-1 viral loads will be
monitored on a regular and continual basis. The main outcome measures are ones of safety
and tolerability: serious adverse events (including all deaths, serious AIDS defining
events, and discontinuations for any reason), injection reconstitution fatigue.
To be eligible for this trial, patients must fulfill all inclusion criteria listed below:
1. Male and female HIV-1 infected adults or adolescents (greater than or equal to 16
years of age).
2. CD4 lymphocyte count less than or equal to 100 cells/mm(3) and HIV-1 RNA viral load
greater than or equal to 10,000 copies/mL while on HAART (latest available
measurement must be within the last 90 days).
3. Patients must be limited by the current commercially available antiretroviral agents
or agents available via Early Access or Compassionate Use Programs as per the
judgment of the investigator OR patients with advanced disease and most in need
defined as prior documented drug resistance or have documented evidence of greater
than 6 months prior experience to each of the three classes of ARV's.
4. Patients must be able and willing to provide written informed consent (for patients
less than 18 years of age, a parent or legal guardian must also sign the Informed
5. Women of childbearing potential must have a documented negative pregnancy test at
baseline and ensure that two reliable forms of contraception are being used,
including a barrier method, for the duration of the study, and for 90 days after the
last dose of study medication.
Patients meeting any of the following exclusion criteria will not be eligible for
participation in this trial:
1. Female patients who are pregnant, breast-feeding, or who plan to become pregnant or
breast-feed during the study.
2. Any current clinical or laboratory parameter of ACTG grade 4. Asymptomatic grade 4
abnormalities will be permitted, at the discretion of the investigator, if the
potential benefit of treatment outweighs the potential risk.
3. Evidence of ongoing alcohol and/or drug or substance abuse that, in the judgment of
the investigator, would result in the patient being unreliable in fulfilling the
conditions of this protocol.
4. Prior non-adherence to antiretroviral treatment regimens that, in the judgment of the
investigator, resulted in the patient's failing prior regimens and which would likely
result in the patient being unreliable in fulfilling the conditions of this protocol.
5. Inability to self-inject Fuzeon (enfuvirtide) as indicated in the protocol, unless a
reliable caregiver is willing, able, and available to provide this service on a
continuous basis for the duration of the study.
6. Evidence of active, untreated opportunistic infection, intercurrent illness, drug
toxicity or any other condition such that, in the judgment of the investigator, the
patient would not be able to continue or take a prescribed antiretroviral regimen.