A Phase I/II Double-Blind Controlled Trial to Determine the Safety and Immunogenicity of HIV-1 MN rgp160 Immuno AG Vaccine Therapy in HIV-Infected Individuals With Greater Than or Equal to 500/mm3 CD4+ T Cells and 200-400/mm3 CD4+ T Cells
Study Details
Study Description
Brief Summary
To evaluate the safety and immunogenicity of HIV-1 MN rgp160 (Immuno-AG) in HIV-infected patients. To evaluate the immunogenicity of HIV-1 MN rgp160 immunogen by lymphocyte proliferation, specific antibody responses, and DTH reaction. To describe the durability of the immunogen in patients who respond to the first 7 injections when they are boosted every 8 weeks for an additional 6-12 months [AS PER AMENDMENT 11/12/96: stratum 1 patients only]. To describe the ability of the immunogen to induce a response after an additional 6-12 months of injections among patients who did not respond to the first 7 injections [AS PER AMENDMENT 11/12/96: stratum 1 patients only].
HIV-specific cellular immune responses appear to play an important role in HIV disease progression since both T helper and cytotoxic function against HIV decrease with disease progression.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
HIV-specific cellular immune responses appear to play an important role in HIV disease progression since both T helper and cytotoxic function against HIV decrease with disease progression.
Patients with CD4 counts greater than or equal to 500 cells/mm3 are randomized to receive HIV-1 MN rgp160 (Immuno-AG) or control. Patients with CD4 counts 50-499 cells/mm3 receive didanosine (ddI) and are then randomized to receive ddI plus vaccine or control. Vaccine or control is given every 4 weeks for 7 injections, then every 8 weeks for 6-12 months or until 1 year after the last patient is randomized. AS PER AMENDMENT 11/12/96: Stratum 1 is composed of 16 subjects with CD4+ T cells greater than or equal to 500 mm3. These subjects are randomized to vaccine therapy or vaccine control. HIV-1 MN rgp160 vaccine or control is given every 4 weeks for 7 injections (Schedule 1), then every 8 weeks until 52 weeks after the last subject has been randomized to stratum 1 (Schedule 2). Stratum 1 patients receive ddI or d4T only if their CD4 cell count has a sustained decrease on 2 consecutive occasions 10-14 days apart and/or HIV/RNA plasma viral load increases to greater than 10,000 copies/ml on 2 consecutive occasions 10-14 days apart. Stratum 2 is composed of 30 subjects with CD4+ T cells 200-400/mm3; accrual to this stratum was activated based on preliminary results from stratum 1 (closed as of 4/5/97). Patients on stratum 2 (open as of 3/4/97) initially receive ritonavir at escalating doses for 2 weeks. Subjects then have ddI and d4T added to the regimen for 7 weeks. Subjects are then randomized to vaccine therapy or vaccine control every 4 weeks for 7 injections, with ritonavir/ddI/d4T continued during vaccine therapy.
AS PER AMENDMENT 3/23/98: As of 6/1/98 vaccine consists of sodium chloride for injection (USP).
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria
Concurrent Medication:
Allowed:
-
ddI [AS PER AMENDMENT 11/12/96: and d4T]. (Note:
-
Patients in the stratum receiving only vaccine or control may take ddI [AS PER
AMENDMENT 11/12/96:
-
and d4T] ONLY IF their CD4 counts have shown a sustained decrease on two consecutive occasions 10-14 days apart.)
-
PCP prophylaxis.
-
Treatment for acute conditions, as indicated.
AS PER AMENDMENT 11/12/96:
- Co-enrollment on other research trials.
Patients must have:
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HIV positivity.
-
Asymptomatic disease.
-
CD4 count >= 50 cells/mm3 (CD4 count must be 50-499 cells/mm3 in patients receiving ddI plus vaccine or control, and must be >= 500 cells/mm3 in patients receiving vaccine or control only)
[AS PER AMENDMENT 11/12/96:
-
CD4 count >= 500 cells/mm3 for stratum 1 patients and 200-400 for stratum 2 patients].
-
HLA A2 positive documentation.
-
An Epstein Barr virus B cell line established within 90 days prior to study entry.
-
Consent of parent or guardian if less than 18 years of age.
NOTE:
- Study is NOT approved for prisoner participation.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
-
Medical contraindication to study participation or inability to comply with study requirements.
-
Grade 2 or worse peripheral neuropathy (applicable only to patients receiving ddI plus vaccine or control).
Concurrent Medication:
Excluded:
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Immunomodulating agents, such as inosiplex, ditiocarb sodium, lithium, interferons, interleukin-2, and systemic steroids.
-
Any antiretroviral therapy that may increase the risk of peripheral neuropathy (e.g., stavudine, zalcitabine [AS PER AMENDMENT 11/12/96:
-
e.g., zalcitabine or lamivudine]).
-
Agents such as IV pentamidine that may increase the risk of pancreatitis.
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Standard of care vaccines (in patients receiving vaccine) [AS PER AMENDMENT 11/12/96:
-
Standard of care immunizations are permitted 60 days before Schedule 1 vaccine therapy and during Schedule 2 vaccine therapy (but not within 2 weeks of study immunization)].
AS PER AMENDMENT 11/12/96:
- Rifabutin, disulfiram (antabuse), or other medication with similar effects, including metronidazole.
6.AS PER AMENDMENT 11/12/96:
-
The following are prohibited in patients receiving ritonavir:
-
amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, encainide, flecainide, meperidine, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, terfenadine, alprazolam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, and zolpidem.
Patients with the following prior conditions are excluded:
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History of grade 2 or worse liver abnormality.
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Known allergy to vaccine components.
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Chronic diarrhea persisting for 4 or more weeks within 30 days prior to study entry.
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History of pancreatitis (applicable only to patients receiving ddI plus vaccine or control). [AS PER AMENDMENT 11/12/96:
-
History of chronic pancreatitis or history of acute pancreatitis within 2 years prior to entry (stratum 2 patients only).]
Prior Medication:
Excluded:
- Any prior anti-HIV vaccines.
Excluded within 90 days prior to study entry:
-
Immunomodulating agents, such as Inosiplex, ditiocarb sodium, lithium, interferons, interleukin-2, and systemic steroids.
-
Any antiretroviral therapy that may increase the risk of peripheral neuropathy (e.g., stavudine, zalcitabine [AS PER AMENDMENT 11/12/96:
-
e.g., zalcitabine or lamivudine]).
-
Agents such as IV pentamidine that may increase the risk of pancreatitis.
-
Any treatment for an AIDS-defining illness (applicable ONLY to patients in the stratum receiving ddI plus vaccine or control).
Excluded within 6 months prior to study entry:
-
Any other antiretrovirals or immunomodulators besides those mentioned above.
-
Allergy desensitization or other vaccines [AS
PER AMENDMENT 11/12/96:
- excluded within 60 days prior to entry].
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford CRS | Stanford | California | United States | 943055107 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Bristol-Myers Squibb
- Immuno-US
Investigators
- Study Chair: Kundu Smriti,
- Study Chair: Merigan T,
Study Documents (Full-Text)
None provided.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)
- Kundu-Raychaudhuri S, Sevin A, Kilgo P, Nokta M, Pollard RB, Merigan TC. Effect of therapeutic immunization with HIV type 1 recombinant glycoprotein 160 ImmunoAG vaccine in HIV-infected individuals with CD4+ T cell counts of >or=500 and 200-400/mm3 (AIDS Clinical Trials Group Study 246/946). AIDS Res Hum Retroviruses. 2001 Oct 10;17(15):1371-8.
- ACTG 246/946
- 11223
- 11499