A Phase I Study of the Safety and Pharmacokinetics of Recombinant Human CD4 Immunoglobulin (rCd4-IgG) Administered by Intravenous Bolus in Patients With AIDS and AIDS Related Complex

June 23, 2005 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To study the safety and pharmacokinetics (blood levels) of recombinant human CD4 immunoglobulin (rCd4-IgG) in patients with AIDS or AIDS related complex (ARC) who have failed or declined therapy with zidovudine (AZT). An additional goal of the study is to obtain a preliminary indication of the antiviral effects of Cd4-IgG in patients with AIDS or ARC.

Other approaches in addition to existing treatment of HIV infection need to be evaluated. One approach may be to block HIV infection by interrupting the assembly of the virus within the cell or the budding of virus from the membrane of the infected cell. In addition, blocking the attachment of HIV to its cellular receptor may offer another point of attack. HIV binds to the CD4 receptor on the target T4 lymphocyte and the envelope glycoprotein of the virus (gp120) is capable of high affinity binding to CD4. Any agent that prevents the attachment of gp120 to the CD4 receptor should be able to block virus transmission and spread. Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of binding to HIV envelope protein (gp120) and inhibiting HIV infectivity in test tube studies. Potential therapeutic benefit in patients with HIV infection could be derived from either or both of these biologic effects. In order to extend the length of time that rCD4 stays in the body, the compound has been modified by combining it with a human immunoglobulin of the IgG1 class (IgG).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Other approaches in addition to existing treatment of HIV infection need to be evaluated. One approach may be to block HIV infection by interrupting the assembly of the virus within the cell or the budding of virus from the membrane of the infected cell. In addition, blocking the attachment of HIV to its cellular receptor may offer another point of attack. HIV binds to the CD4 receptor on the target T4 lymphocyte and the envelope glycoprotein of the virus (gp120) is capable of high affinity binding to CD4. Any agent that prevents the attachment of gp120 to the CD4 receptor should be able to block virus transmission and spread. Recently, scientists have succeeded in producing highly purified recombinant soluble human CD4. Recombinant CD4 is capable of binding to HIV envelope protein (gp120) and inhibiting HIV infectivity in test tube studies. Potential therapeutic benefit in patients with HIV infection could be derived from either or both of these biologic effects. In order to extend the length of time that rCD4 stays in the body, the compound has been modified by combining it with a human immunoglobulin of the IgG1 class (IgG).

Each patient receives rCd4-IgG at a fixed dose level once weekly by intravenous bolus for 12 weeks. Four patients (two per center) are entered at each dose level starting with the lowest dose. Dose escalation proceeds until a maximum tolerated dose (MTD) is defined. AMENDED: Includes, as of 891201, an ancillary study entitled "A Study of Recombinant CD4-Immunoglobulin G (CD4-IgG) Levels in Cerebral Spinal Fluid after rCD4-IgG is Administered by Intravenous Bolus in Patients With AIDS and AIDS-Related Complex". This involves selected patients, at the discretion of the Investigator. AMENDED: 900110 To increase the dose and frequency of administration of rCD4-IgG, based on preliminary results of pharmacokinetic analyses from Phase I studies in humans. Each patient receives rCD4-IgG therapy at a fixed dose level 1x, 2x, or 3x weekly by intravenous bolus for 12 weeks. Follow-up is extended to 8 weeks. Total target accrual is 25 - 28 weeks. AMENDED: 900824 Extension of the Phase I study of the safety and efficacy of CD4-IgG in patients with HIV infection. Each patient receives one of two fixed doses by IV bolus injection twice per week for 12 weeks. 20 to 30 patients to be enrolled. Pharmacokinetics will be evaluated. Clinical safety and antiviral effects will be assayed.

Study Type

Interventional

Enrollment

60

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
    • California
      • Stanford, California, United States, 94305
        • Stanford Univ School of Medicine
    • Washington
      • Seattle, Washington, United States, 98105
        • Univ of Washington

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients must fulfill the following criteria:

  • Diagnosis of AIDS or AIDS-related complex, according to CDC criteria, in previously documented HIV seropositive individuals.
  • Failure to tolerate or respond to zidovudine (AZT) therapy for HIV infection or a decision to decline such therapy.
  • Willingness to abstain from all other experimental therapy for HIV infection during study period.
  • Life expectancy of at least 3 months.
  • Patients must be able to sign a written informed consent form.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Serious active opportunistic infection or malignancies not specifically allowed.

Concurrent Medication:

Excluded:

  • Oral or intravenous acyclovir for herpes.
  • Zidovudine (AZT).
  • Interferon.
  • Corticosteroids.
  • Nonsteroidal anti-inflammatory agents (NSAIDS).
  • Intravenous acyclovir.
  • Other known immunomodulatory agents.
  • Other experimental therapy.

Patients with the following are excluded:

  • Serious active opportunistic infection or malignancies not specifically allowed.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Zidovudine (AZT).
  • Chemotherapy.
  • Immunomodulatory agents.
  • Other experimental therapy.

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

Collaborators and Investigators

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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Genentech, Inc.

Investigators

  • Study Chair: L Corey
  • Study Chair: A Collier

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 Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

June 24, 2005

Last Update Submitted That Met QC Criteria

June 23, 2005

Last Verified

January 1, 1991

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 121
  • DO136g

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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