Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000976
Status:
COMPLETED
Last Update Posted:
2008-08-06
First Post:
1999-11-02
Brief 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
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
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
Status:
COMPLETED
Status Verified Date:
1994-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
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 mcgkg 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 pgm 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
AMENDED Previously rCD4-IgG had been administered on a mcgkg 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 pgm 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
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| D0156g | None | None | None |