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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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
gp160 Vaccine (MicroGeneSys)
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring Vaccines, Synthetic, Injections, Intradermal, HIV Antigens, HIV Seropositivity, HIV-1, Drug Evaluation, Hypersensitivity, Delayed, AIDS Vaccines, HIV Therapeutic Vaccine

Eligibility Criteria

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

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).

Sites / Locations

  • NY Univ. HIV/AIDS CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Protein Sciences Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00000667
Brief 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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 1993 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Protein Sciences Corporation

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Vaccines, Synthetic, Injections, Intradermal, HIV Antigens, HIV Seropositivity, HIV-1, Drug Evaluation, Hypersensitivity, Delayed, AIDS Vaccines, HIV Therapeutic Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
20 (false)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
gp160 Vaccine (MicroGeneSys)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katzenstein DA
Official's Role
Study Chair
Facility Information:
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
background
PubMed Identifier
10634195
Citation
Katzenstein DA, Kundu S, Spritzler J, Smoller BR, Haszlett P, Valentine F, Merigan TC. Delayed-type hypersensitivity to recombinant HIV envelope glycoprotein (rgp160) after immunization with homologous antigen. J Acquir Immune Defic Syndr. 1999 Dec 1;22(4):341-7. doi: 10.1097/00126334-199912010-00004.
Results Reference
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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

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