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A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)

Primary Purpose

HIV Infections

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CD4 Antigens
Zidovudine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Acquired Immunodeficiency Syndrome, Antigens, CD4, AIDS-Related Complex, Zidovudine

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Nystatin or clotrimazole for suppression of oral thrush. Aerosolized pentamidine as chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). Trimethoprim / sulfamethoxazole (TMP / SMX) for patients who are clinically and hematologically stable on TMP / SMX PCP prophylaxis. Patients must have the following: Diagnosis of AIDS or advanced AIDS related complex (ARC). CD4 cell count < 300 cells/mm3. Ability to understand and sign the consent form. Risk Behavior: Allowed: History of drug abuse with current abstinence or enrollment in a methadone treatment program. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Concurrent Medication: Excluded: Investigational drugs. Antiretroviral agents such as dextran sulfate or AL721. Cytotoxic chemotherapy. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Prior Medication: Excluded: Zidovudine (AZT) for longer than 30 days or prior treatment with AZT for < 30 days if discontinued for toxicity due to AZT. Excluded within 30 days of study entry: Immunomodulators. Previous participation in any group of another part of this study. For example, patients treated in Part 1A of this study may not reenter the study to be treated in Part 2. Chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy. Active use of illicit drugs or abuse of alcohol at time of protocol entry.

Sites / Locations

  • Tulane Univ School of Medicine
  • Bellevue Hosp / New York Univ Med Ctr

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
March 11, 2011
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT00000659
Brief Title
A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)
Official Title
A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)
Study Type
Interventional

2. Study Status

Record Verification Date
July 1990
Overall Recruitment Status
Terminated
Study Start Date
undefined (undefined)
Primary Completion Date
July 1990 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Biogen

4. Oversight

5. Study Description

Brief Summary
Part 1A: To find the dose of zidovudine (AZT) that causes less than a 50 percent drop in HIV-1 p24 antigen levels in patients with AIDS and advanced AIDS related complex (ARC); to determine the pharmacokinetics (blood levels) of rsCD4 administered in combination with AZT. Parts 1B and 2: To test for additive or synergistic activity between rsCD4 and AZT as judged by falls in HIV-1 p24 antigen levels; and to evaluate the safety of rsCD4 and AZT in patients with AIDS and advanced ARC. AZT has been shown to be effective in the treatment of AIDS and advanced ARC but not without toxicity. The most clinically significant toxicity is dose related inhibition of bone marrow function. Furthermore, HIV-1 isolates from patients treated for more than 6 months with AZT have now been found which appear to have reduced sensitivity to AZT. The incidence of toxicity and occurrence of virus with reduced sensitivity to AZT may result in the inability to administer AZT long-term to patients with AIDS and advanced ARC. Recombinant soluble CD4 (rCD4) has shown antiretroviral effects and has been shown to be safe when given to AIDS and ARC patients either as a single agent or in combination with AZT.
Detailed Description
AZT has been shown to be effective in the treatment of AIDS and advanced ARC but not without toxicity. The most clinically significant toxicity is dose related inhibition of bone marrow function. Furthermore, HIV-1 isolates from patients treated for more than 6 months with AZT have now been found which appear to have reduced sensitivity to AZT. The incidence of toxicity and occurrence of virus with reduced sensitivity to AZT may result in the inability to administer AZT long-term to patients with AIDS and advanced ARC. Recombinant soluble CD4 (rCD4) has shown antiretroviral effects and has been shown to be safe when given to AIDS and ARC patients either as a single agent or in combination with AZT. Part 1A: Twenty p24+ patients with AIDS or advanced ARC are randomized to 4 dosing groups of 5 patients each. Patients are treated with AZT for 6 weeks at ranging doses to determine a minimally effective dose (MED). At the end of week 6, each patient is sequentially assigned to 1 of 5 groups of rCD4 / AZT combination treatment. The first 3 patients to complete treatment through week 6 are treated in group A, the next 3 patients in group B, and so on. The treatment period is 4 weeks. Each patient continues on his or her AZT dose as initially administered. The highest dose of AZT that produces less than a 50 percent drop in HIV-1 p24 antigen levels in at least 3 of 5 patients over 6 weeks will be the MED of AZT and will be known as the AZT MED. After the MED is determined, Part 1B begins. Part 1B: 20 patients are randomized to 2 different dosing groups: Group 5: AZT MED (weeks 1 to 8), then AZT MED plus rCD4 (weeks 9 to 16); Group 6: AZT MED plus rCD4 (weeks 1 to 8), then AZT MED (weeks 9 to 16). Part 2: Part 2 begins once accrual to Part 1B is completed. If fewer than 10 of 20 patients exhibit a drop of at least 50 percent in p24 antigen level after receiving AZT and rsCD4 combination treatment, entry to Part 2 will be interrupted and the study design will be reevaluated. In Part 2, 10 patients are randomly assigned to one of four groups. Patients within each group receive two 8 week treatment courses. These two treatment courses are 8 weeks with the AZT MED alone, and 8 weeks of treatment with the combination of the AZT MED plus rCD4.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Acquired Immunodeficiency Syndrome, Antigens, CD4, AIDS-Related Complex, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
80 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
CD4 Antigens
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Nystatin or clotrimazole for suppression of oral thrush. Aerosolized pentamidine as chemoprophylaxis for Pneumocystis carinii pneumonia (PCP). Trimethoprim / sulfamethoxazole (TMP / SMX) for patients who are clinically and hematologically stable on TMP / SMX PCP prophylaxis. Patients must have the following: Diagnosis of AIDS or advanced AIDS related complex (ARC). CD4 cell count < 300 cells/mm3. Ability to understand and sign the consent form. Risk Behavior: Allowed: History of drug abuse with current abstinence or enrollment in a methadone treatment program. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Concurrent Medication: Excluded: Investigational drugs. Antiretroviral agents such as dextran sulfate or AL721. Cytotoxic chemotherapy. Concurrent Treatment: Excluded: Radiation therapy. Patients with the following are excluded: Malignancies other than Kaposi's sarcoma. AIDS dementia which, in the opinion of the investigator, precludes patients from giving fully informed consent or from complying fully with the requirements of this protocol. Active infection with an opportunistic pathogen requiring ongoing therapy. Preexisting antibodies to rCD4. Prior Medication: Excluded: Zidovudine (AZT) for longer than 30 days or prior treatment with AZT for < 30 days if discontinued for toxicity due to AZT. Excluded within 30 days of study entry: Immunomodulators. Previous participation in any group of another part of this study. For example, patients treated in Part 1A of this study may not reenter the study to be treated in Part 2. Chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy. Active use of illicit drugs or abuse of alcohol at time of protocol entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
RT Schooley
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
DD Ho
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
TC Merigan
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
L Laubenstein
Official's Role
Study Chair
Facility Information:
Facility Name
Tulane Univ School of Medicine
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States

12. IPD Sharing Statement

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A Phase II Trial of rsCD4 and AZT in Patients With AIDS or Advanced AIDS Related Complex (ARC)

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