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Sponsors and Collaborators: |
National Institute of Allergy and Infectious Diseases (NIAID) Genentech |
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Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00000976 |
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 |
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HIV Infections |
Drug: CD4-IgG Drug: Zidovudine |
Phase I |
Study Type: | Interventional |
Study Design: | 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 |
Estimated Enrollment: | 40 |
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
Patients must have the following:
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions or symptoms are excluded:
Concurrent Medication:
Excluded:
Patients with the following are excluded:
Prior Medication:
Excluded:
Prior Treatment:
Excluded within the past 3 months:
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 |
Study Chair: | D Richman | |
Study Chair: | M Fischl |
Study ID Numbers: | ACTG 134, D0156g |
Study First Received: | November 2, 1999 |
Last Updated: | August 5, 2008 |
ClinicalTrials.gov Identifier: | NCT00000976 |
Health Authority: | United States: Federal Government |
Recombinant Proteins Injections, Intravenous IgG Drug Evaluation Administration, Oral |
Acquired Immunodeficiency Syndrome Antigens, CD4 Zidovudine Carrier Proteins |
Sexually Transmitted Diseases, Viral Acquired Immunodeficiency Syndrome Zidovudine AIDS-Related Complex Immunologic Deficiency Syndromes Virus Diseases Antibodies |
HIV Infections Sexually Transmitted Diseases Immunoglobulin G CD4 Immunoadhesins Retroviridae Infections Immunoglobulins |
Antimetabolites Anti-Infective Agents RNA Virus Infections Anti-HIV Agents Slow Virus Diseases Immune System Diseases Immunologic Factors Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |
Enzyme Inhibitors Infection Antiviral Agents Pharmacologic Actions Reverse Transcriptase Inhibitors Anti-Retroviral Agents Therapeutic Uses Lentivirus Infections Nucleic Acid Synthesis Inhibitors |