A Phase I Study of the Safety and Pharmacokinetics of Recombinant Human CD4-Immunoglobulin G (rCD4-IgG) Administered by Intravenous Bolus Injection in Combination With Oral Zidovudine in Patients With AIDS and AIDS-Related Complex

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000976
First received: November 2, 1999
Last updated: August 5, 2008
Last verified: December 1994
  Purpose

To determine the safety profile of recombinant human CD4-immunoglobulin G (CD4-IgG) and zidovudine (AZT) combination therapy in patients with AIDS or AIDS-related complex (ARC); to assess pharmacokinetic (blood level) properties of CD4-IgG in combination with AZT; and to obtain preliminary indication of the antiviral and immunologic effects of CD4-IgG in combination with AZT in patients with AIDS and ARC.

Treatment of AIDS has been directed toward the underlying retroviral infection as well as toward specific opportunistic infections and malignancies that are associated with the syndrome. The most extensively studied drugs are reverse transcriptase inhibitors such as AZT and other nucleoside analogs, including didanosine (ddI) and dideoxycytidine (ddC). The most extensive clinical experience has been achieved with AZT. These clinical trials indicated a decreased incidence of opportunistic infection and increased survival in patients with AIDS. However, AZT treatment is associated with dose-limiting toxicities. Additionally, identification of resistance to AZT has increased the need to test the effectiveness of AZT in combination with other drugs. CD4-IgG 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 may be derived from CD4-IgG.


Condition Intervention Phase
HIV Infections
Drug: CD4-IgG
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study of the Safety and Pharmacokinetics of Recombinant Human CD4-Immunoglobulin G (rCD4-IgG) Administered by Intravenous Bolus Injection in Combination With Oral Zidovudine in Patients With AIDS and AIDS-Related Complex

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 40
Detailed Description:

Treatment of AIDS has been directed toward the underlying retroviral infection as well as toward specific opportunistic infections and malignancies that are associated with the syndrome. The most extensively studied drugs are reverse transcriptase inhibitors such as AZT and other nucleoside analogs, including didanosine (ddI) and dideoxycytidine (ddC). The most extensive clinical experience has been achieved with AZT. These clinical trials indicated a decreased incidence of opportunistic infection and increased survival in patients with AIDS. However, AZT treatment is associated with dose-limiting toxicities. Additionally, identification of resistance to AZT has increased the need to test the effectiveness of AZT in combination with other drugs. CD4-IgG 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 may be derived from CD4-IgG.

AMENDED: Previously, rCD4-IgG had been administered on a mcg/kg basis. Subjects now receive rCD4-IgG as a fixed dose. Changes to the maintenance schedule were made to accommodate the new dosages. Original design: This study is divided into two parts: A pharmacokinetic evaluation, and a safety evaluation. The pharmacokinetic evaluation is done in selected patients. For the safety evaluation patients will receive rCD4-IgG at a fixed dose level twice weekly by intravenous bolus injection (over 1 minute) for 12 weeks. Zidovudine (AZT) is administered orally 3 times daily at one of two dose levels. Eight subjects, at least 4 of whom with p24 levels greater than 75 pg/m, are entered at each dose level of CD4-IgG beginning with dose level 1. If 3 or more patients at a dose level experience grade 3 or 4 toxicity then no further patients will be added to that or higher dose levels. Pharmacokinetics of CD4-IgG alone and in combination with AZT is evaluated in patients at dose level 2 only. Patients receive one IV bolus of CD4-IgG on day 1 and samples are drawn beginning 15-30 minutes prior to the CD4-IgG injection. There is an 8 day washout period. Beginning on day 9 and continuing through day 24, patients receive AZT daily. CD4-IgG is administered by IV bolus on day 16. Samples are drawn beginning 15-30 minutes prior to the injection of CD4-IgG. The pharmacokinetic evaluation terminates 8 days after the second CD4-IgG injection (day 24). Extended treatment will be made available to patients at the discretion of the Principal Investigator.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Topical acyclovir.

Patients must have the following:

  • HIV seropositivity.
  • Life expectancy of at least 3 months.
  • No white or red blood cell casts in urine.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Serious active opportunistic infection or malignancies other than Kaposi's sarcoma.
  • Kaposi's sarcoma requiring therapy, tumor-associated edema, or visceral disease.

Concurrent Medication:

Excluded:

  • Intravenous acyclovir for Herpes.
  • Interferon.
  • Systemic corticosteroids.
  • Nonsteroidal anti-inflammatory agents.
  • Intravenous acyclovir.
  • Other known immunomodulatory agents.
  • Dideoxycytosine (ddC), didanosine (ddI).
  • Other nucleoside analogs not specifically allowed.
  • Other experimental therapy.

Patients with the following are excluded:

  • Serious active opportunistic infection or malignancies other than Kaposi's sarcoma.
  • More than 120 days (total) of prior zidovudine (AZT) therapy.
  • Currently receiving intravenous acyclovir for Herpes.

Prior Medication:

Excluded:

  • > 120 days total of prior zidovudine (AZT) therapy.
  • Excluded within 3 weeks of study entry:
  • Immunomodulatory agents.
  • Other experimental therapy.

Prior Treatment:

Excluded within the past 3 months:

  • Transfusion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000976

Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Massachusetts
Univ of Massachusetts
Worcester, Massachusetts, United States, 01655
Sponsors and Collaborators
Genentech
Investigators
Study Chair: D Richman
Study Chair: M Fischl
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000976     History of Changes
Other Study ID Numbers: ACTG 134, D0156g
Study First Received: November 2, 1999
Last Updated: August 5, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Recombinant Proteins
Injections, Intravenous
IgG
Drug Evaluation
Administration, Oral
Acquired Immunodeficiency Syndrome
Antigens, CD4
Zidovudine
Carrier Proteins

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Immunoglobulin G
Immunoglobulins
Antibodies
CD4 Immunoadhesins
Zidovudine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 26, 2014