Safety and Efficacy Study of Etanercept (Enbrel) on the Response Rate of HIV-infected Subjects

July 21, 2009 updated by: Georgetown University

A Phase I Pilot Study to Evaluate Safety and Efficacy of Etanercept (Enbrel) on the Response Rate of HIV-infected Subjects Who Are in Virologic Failure and Who Have Failed to Respond to Standard Antiretroviral Therapy

The purpose of conducting this already-FDA approved Phase I clinical trial is to evaluate the safety and efficacy of etanercept (Enbrel) on the response rate in HIV-infected subjects who have failed to respond to conventional antiretroviral (HAART) therapy and for whom no alternative therapy exists. The greatest challenge faced by HIV-treating clinicians today is the management of virologic failure and metabolic complications of anti-HIV treatment. Treatment failure can occur because of non-compliance, drug discontinuation, lack of drug potency, inadequate drug plasma concentration or drug resistance. Of these, drug resistance remains the single most important reason for virological failure and rapidly limits treatment options.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

I. Background and Rationale:

The greatest challenge faced by HIV-treating clinicians today is the management of virologic failure and metabolic complications of anti-HIV treatment. Treatment failure can occur because of non-compliance, drug discontinuation, lack of drug potency, inadequate drug plasma concentration or drug resistance. Of these, drug resistance remains the single most important reason for virological failure and rapidly limits treatment options. Virus resistance to all three major antiretroviral drug classes is now being reported even in primary seroconverters. Although highly-active antiretroviral (ARV) therapy (HAART) has led to a sharp decline in AIDS-related morbidity and mortality, treatment failure is a common, significant problem and as many as 50% of patients have detectable plasma HIV RNA despite being on combination ARV therapy. Salvage therapy is the term commonly used to define the approach taken when previous anti-HIV treatments fail to achieve desired goals, which include: 1) undetectable viral load; 2) CD4 cell levels below 200 cells/mm3; and, 3) the prevention of HIV disease progression. It is one of the most difficult situations to face as a patient, and one of the most problematic challenges for health-care providers. Although this state of treatment failure is sometimes euphemistically referred to as "management of treatment-experienced patients," many HIV positive patients, having already exhausted the benefits of at least a few drug combinations, think of their next regimen as salvage or "rescue" therapy. Some physicians argue that due to cross-resistance among different drugs within the same class, people with HIV infection have only one good shot at treating it, and that any treatment regimen beyond the first is therefore salvage therapy. Others see salvage therapy as literally the end of the line--when an individual's HIV has developed extensive resistance to all currently available treatments. But most providers consider salvage therapy to be somewhere in between these extremes. Data on salvage therapy mostly comes from anecdotal reports and retrospective cohort studies. With a paucity of clinical trial data, clinicians are often forced to prescribe unproven regimens based on what is anticipated about cross-resistance and drug interactions. It is important, therefore, that new agents and new approaches continue to be developed as an increasing number of patients in practice have exhausted all treatment options.

The rationale of this study is based upon the existing literature which indicates that many of the manifestations and subsequent clinical deterioration of HIV-infected individuals are related to the immune dysfunction seen in HIV disease, many of which are caused by the overproduction of proinflammatory cytokines, most notable of which is the excessive production of TNF-α. It is further postulated that removal of this TNF-α by a commercially available TNF-α-binding medication [ENBREL (etanercept)] may provide therapeutic benefit for HIV-infected patients who have failed to respond to standard antiretroviral therapy.

II. Goal and Objectives:

The purpose of the project is to assess the safety profile and efficacy of a soluble p75 tumor necrosis factor (TNF) receptor: Fc fusion protein (Enbrel; Amgen, (etanercept) Thousand Oaks, CA) [i.e. anti TNF-α] on the response rate of "salvage patients" who are in virologic failure and who have failed to respond to standard antiretroviral therapy.

The protocol will evaluate:

  1. Changes in CD4 T-cell enumeration, viral load, and soluble immune activation markers in HIV-infected patients from baseline to week 24 following treatment with anti-TNF-α.
  2. Safety and tolerability of anti-TNF-α with respect to treatment-limiting symptoms and laboratory adverse events through week 24.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 18 and 60 years.
  • Confirmed diagnosis of HIV-1 infection, as documented by any licensed ELISA test kit, and confirmed by Western blot at any time prior to study entry, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA.
  • Prior antiretroviral therapy, defined as: Receipt of at least two separate protease inhibitor (PI)-containing regimens (minimum 12 weeks) which was changed because of virological failure (per subject or physician history) or detectable plasma HIV-1 RNA AND A minimum of 1 year total prior antiretroviral experience.
  • A CD4 count of > 200.
  • Signed a written informed consent prior to initiation of any study related procedures.
  • All subjects should continue taking the same antiretroviral regimen between the screening and entry visits.

Exclusion Criteria:

  • History or suspicion of active tuberculosis or a prior history of being treated for tuberculosis.
  • Documented history of sepsis.
  • Known hypersensitivity to ENBREL or any of its components.
  • Patients on concomitant immunosuppressive therapy, e.g., steroids, cyclosporine, etc.
  • Any condition which may interfere with the trial, including the patient's mental ability to follow protocol instructions.
  • Patients with heart failure or a history of congestive heart failure.
  • Renal insufficiency (creatinine >2.5 mg/dL)
  • Women of child bearing potential who are not willing to avoid pregnancy for the duration of the study and 3 months thereafter.
  • Inability or unwillingness to take appropriate prophylaxis for opportunistic infections (i.e., PCP toxoplasmosis, etc.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Collaborators

Advanced Biotherapy, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

October 1, 2004

Study Registration Dates

First Submitted

September 16, 2004

First Submitted That Met QC Criteria

September 17, 2004

First Posted (Estimate)

September 20, 2004

Study Record Updates

Last Update Posted (Estimate)

July 22, 2009

Last Update Submitted That Met QC Criteria

July 21, 2009

Last Verified

September 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB 03-365

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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