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Immunomodulation of HIV-1 Infected Individuals With PEG-Interleukin-2
This study has been completed.
First Received: November 2, 1999   Last Updated: June 23, 2005   History of Changes
Sponsored by: Rockefeller University
Information provided by: NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier: NCT00002017
  Purpose

To evaluate the safety and immunological effects of polyethylene glycolated-interleukin-2 (PEG-IL-2) on asymptomatic (without symptoms) HIV-seropositive patients who are taking zidovudine (AZT). To enhance measures of immune function with well-tolerated doses of PEG-IL-2, an immunomodulator, in a regimen designed to allow its use in outpatients with normal daily activity (i.e., full-time employment, etc.). Recombinant IL-2 (without PEG modification) was administered to HIV-infected patients by daily intradermal injection. At the low doses used, this was non-toxic, well-tolerated, and gave a systemic response as measured by natural killer cell and lymphokine-activated killer cell activity, but required daily administration. In the current study, the PEG modification of IL-2 is used since it has a much longer prolonged half-life compared with the non-PEG compound, without loss of functional activity.


Condition Intervention
HIV Infections
Drug: Interleukin-2, Polyethylene Glycolated

Study Type: Interventional
Study Design: Treatment, Dose Comparison
Official Title: Immunomodulation of HIV-1 Infected Individuals With PEG-Interleukin-2

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Detailed Description:

Recombinant IL-2 (without PEG modification) was administered to HIV-infected patients by daily intradermal injection. At the low doses used, this was non-toxic, well-tolerated, and gave a systemic response as measured by natural killer cell and lymphokine-activated killer cell activity, but required daily administration. In the current study, the PEG modification of IL-2 is used since it has a much longer prolonged half-life compared with the non-PEG compound, without loss of functional activity.

In the first, dose-escalation phase of the study, PEG-IL-2 is injected into the skin of the back by either the intradermal (ID) or subcutaneous (SC) route, to establish an optimal dose (which when given ID results in local induration = or > 25 mm without significant toxicity). The ID and SC routes are compared for systemic effect and toxicity. In the second phase of the study, the PEG-IL-2 is administered for 6-8 weeks using the optimal dosage, frequency, and route determined in the initial phase (probably 2-3 times per week) while local and systemic effects are monitored. These include measures of viral titer, peripheral blood mononuclear cell phenotype, CBC and CD4 counts, and in vitro cytotoxicity assays.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Zidovudine (AZT).
  • Necessary topical agents such as nystatin, clotrimazole, and acyclovir.
  • Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.
  • Oral antibiotics for PCP prophylaxis if hematologically stable for = or > 30 days prior to study entry.
  • Necessary systemic agents for the treatment of other chronic disorders, such as diabetes or asthma.

Patients must have:

  • HIV-1 seropositivity.
  • Asymptomatic.
  • No opportunistic infection for 8 weeks prior to study entry.
  • Been on azidothymidine (AZT) (= or > 500 mg/day) for at least 8 weeks prior to beginning interleukin-2 (IL-2), with stable CD4 cell counts.

Prior Medication:

Allowed:

  • Zidovudine (AZT).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active, life-threatening opportunistic infection (OI) with bacterial, viral, fungal, or protozoan pathogens.
  • Fever = or > 101 F. within 10 days prior to study entry.
  • Significant central nervous system (CNS) disease including AIDS dementia, psychiatric disability, or seizure disorder.
  • Significant cardiac disease (New York Heart Association Stage III or IV).
  • Significant pulmonary disease (Forced Expiratory Volume < 75 percent.
  • Weight loss = or > 10 percent within last 3 months.

Concurrent Medication:

Excluded:

  • Systemic therapy for opportunistic infection (OI).

Patients with the following are excluded:

  • Presence of antibody to interleukin-2 (IL-2).
  • Diseases or symptoms listed in Exclusion Co-Existing Conditions.

Prior Medication:

Excluded within 12 weeks prior to study entry:

  • Other immunomodulators.
  • Corticosteroids.
  • Other experimental therapy.
  • Anti-neoplastic chemotherapy.

Active drug or alcohol abuse.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002017

Locations
United States, New York
Rockefeller Univ
New York, New York, United States, 10021
Sponsors and Collaborators
Rockefeller University
  More Information

Publications:
Teppler H, Montana A, Meyn P, Kaplan G, Cohn ZA. Prolonged immunostimulatory effect of low dose PEG interleukin-2 in HIV-infected individuals. Int Conf AIDS. 1992 Jul 19-24;8(2):B162 (abstract no PoB 3453)

Study ID Numbers: 072A, COH-010-0790
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00002017     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Polyethylene Glycols
Interleukin-2

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Analgesics, Non-Narcotic
Interleukin-2
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Peripheral Nervous System Agents
Analgesics
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Acquired Immunodeficiency Syndrome
Infection
Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases
Sensory System Agents
Analgesics, Non-Narcotic
HIV Infections
Interleukin-2
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Retroviridae Infections

ClinicalTrials.gov processed this record on September 02, 2009