A Phase I/II Dose Escalation Study of Intradermal gp160 to Evaluate Safety, Delayed Type Hypersensitivity (Skin Test) Responses and Immunogenicity in Asymptomatic HIV Seropositive Patients With More Than 400 CD4+ Cells

This study has been completed.
Sponsor:
Collaborator:
Protein Sciences Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000667
First received: November 2, 1999
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

To determine the safety of intradermal gp160 in HIV seropositive individuals who are asymptomatic and have a relatively intact immune system. To determine whether there is evidence of a delayed-type hypersensitivity (DTH) response (a "positive" skin test) in these patients, and also the dose of gp160 that elicits a delayed-type hypersensitivity (DTH) response. Early immunity to HIV may play an important role in the long interval between virus infection and the onset of clinical disease. Immune responses have been demonstrated in HIV-infected individuals within weeks to months of infection. Although none of these responses has been shown to be protective, it is possible that boosting anti-HIV immune responses through immunization may slow the progression of HIV infection. DTH responses to HIV-derived recombinant envelope glycoprotein could provide a means of measuring an important immune function in infected patients, and serve as an easily measured surrogate marker of cellular immunity. In addition to eliciting local, cutaneous DTH responses, intradermal inoculation of skin test antigens may be immunogenic, resulting in new antibody production and cellular immune responses. This study allows direct comparison of gp160 administered intradermally with alum-adjuvanted intramuscular preparation with respect to immunogenicity in HIV seropositive patients.


Condition Intervention Phase
HIV Infections
Biological: gp160 Vaccine (MicroGeneSys)
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I/II Dose Escalation Study of Intradermal gp160 to Evaluate Safety, Delayed Type Hypersensitivity (Skin Test) Responses and Immunogenicity in Asymptomatic HIV Seropositive Patients With More Than 400 CD4+ Cells

Resource links provided by NLM:


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

Estimated Enrollment: 20
Study Completion Date: July 1993
Detailed Description:

Early immunity to HIV may play an important role in the long interval between virus infection and the onset of clinical disease. Immune responses have been demonstrated in HIV-infected individuals within weeks to months of infection. Although none of these responses has been shown to be protective, it is possible that boosting anti-HIV immune responses through immunization may slow the progression of HIV infection. DTH responses to HIV-derived recombinant envelope glycoprotein could provide a means of measuring an important immune function in infected patients, and serve as an easily measured surrogate marker of cellular immunity. In addition to eliciting local, cutaneous DTH responses, intradermal inoculation of skin test antigens may be immunogenic, resulting in new antibody production and cellular immune responses. This study allows direct comparison of gp160 administered intradermally with alum-adjuvanted intramuscular preparation with respect to immunogenicity in HIV seropositive patients.

Each of 10 volunteers is initially injected with the lowest dose of intradermal antigen and the injection site observed at 24, 48, and 72 hours. Clinical and laboratory evaluations are performed 4 and 8 weeks after inoculation. If there is not delayed-type hypersensitivity (DTH) response to the lowest dose, patients are retested at the next dose 8 weeks later and dose escalation is continued at 8-week intervals until (1) there is a DTH response to gp160; or (2) the maximum anticipated dose is reached. In any individual, a higher dosage is administered only if there is no evidence of DTH response. Patients with a DTH may continue to receive booster injections of gp160 at 3 month intervals up to week 70. Patients with an immune response but no DTH may continue to receive injections for an additional year. A second group of 10 asymptomatic individuals are recruited and inoculated with the dose found to bring about either a DTH or lymphocyte proliferative response in 7 of the 10 patients in the first group. If the second group confirms the results of the initial group, the study is amended to include patients with AIDS-related complex (ARC) and AIDS.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Acute use (< 14 days) of acyclovir for Herpes simplex virus infections or ketoconazole for symptomatic Candida infections.

Patients must have the following:

  • Asymptomatic HIV seropositivity.
  • Patients with CD4 counts of 400 - 500 cells/mm3 must be informed of the recommended zidovudine (AZT) therapy and sign an informed consent statement declining AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Systemic symptoms other than lymphadenopathy thought to be due to HIV infection including:
  • Fatigue/malaise of > 1 month duration that interferes with normal activities.
  • Fever of > 100 degrees F persisting for > 15 in a 30-day interval without definable cause.
  • Involuntary weight loss in excess of 10 pounds or > 10 percent of normal weight within a 6-month interval.
  • Diarrhea (> 3 stools/day) persisting for more than 30 days without definable cause.
  • Recurrent oral candidiasis.
  • Multidermatomal herpes zoster.
  • Biopsy proven hairy leukoplakia.
  • Evidence of clinically significant central nervous system dysfunction as assessed by neurological exam.

Concurrent Medication:

Excluded:

  • Antiretroviral agents of proven or potential efficacy.
  • Any potential immunoenhancing or immunosuppressive drugs.

Patients with the following are excluded:

  • Known hypersensitivity to insect cells or baculovirus.
  • Abnormal chest x-ray taken within 3 months of study entry.
  • Systemic symptoms other than lymphadenopathy thought to be due to HIV infection as listed in the patient exclusion coexisting diseases or complications.
  • Evidence of clinically significant central nervous system dysfunction as assessed by neurological exam.
  • Unwilling or unable to give written informed consent.

Prior Medication:

Excluded within 90 days of study entry:

  • Zidovudine (AZT).
  • Didanosine (ddI).
  • Any potential antiretroviral.
  • Immunomodulating agents.

Active substance abuse (either continuing daily alcohol abuse or intravenous drug use).

  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: NCT00000667

Locations
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Sponsors and Collaborators
Protein Sciences Corporation
Investigators
Study Chair: Katzenstein DA
  More Information

Publications:
Katzenstein D, Valentine F, Kundu S, Haslett P, Smith G, Merigan T. Delayed-type-hypersensitivity reactions to intradermal gp160 in HIV infected individuals immunized with gp160. Int Conf AIDS. 1992 Jul 19-24;8(2):A35 (abstract no PoA 2192)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000667     History of Changes
Other Study ID Numbers: ACTG 148, 11123
Study First Received: November 2, 1999
Last Updated: May 21, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Vaccines, Synthetic
Injections, Intradermal
HIV Antigens
HIV Seropositivity
HIV-1
Drug Evaluation
Hypersensitivity, Delayed
AIDS Vaccines
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
HIV Seropositivity
Hypersensitivity
Hypersensitivity, Delayed
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

ClinicalTrials.gov processed this record on July 24, 2014