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
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| ClinicalTrials.gov Identifier: NCT00000822 |
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Recruitment Status :
Completed
First Posted : August 31, 2001
Last Update Posted : October 29, 2021
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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 |
|---|---|---|
| HIV Infections | Drug: Ritonavir Biological: gp160 Vaccine (Immuno-AG) Drug: Stavudine Drug: Didanosine | Phase 1 |
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 Type : | Interventional (Clinical Trial) |
| Enrollment : | 46 participants |
| Masking: | Double |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Completion Date : | May 1999 |
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| Ages Eligible for Study: | 13 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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:
- 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:
- 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.
- 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:
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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:
- History of grade 2 or worse liver abnormality.
- Known allergy to vaccine components.
- Chronic diarrhea persisting for 4 or more weeks within 30 days prior to study entry.
- 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].
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000822
| United States, California | |
| Stanford CRS | |
| Stanford, California, United States, 943055107 | |
| Study Chair: | Kundu Smriti | ||
| Study Chair: | Merigan T |
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00000822 |
| Other Study ID Numbers: |
ACTG 246/946 11223 ( Registry Identifier: DAIDS ES Registry Number ) 11499 ( Registry Identifier: DAIDS ES Registry Number ) |
| First Posted: | August 31, 2001 Key Record Dates |
| Last Update Posted: | October 29, 2021 |
| Last Verified: | October 2021 |
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Vaccines, Synthetic Didanosine Drug Therapy, Combination HIV Envelope Protein gp160 Acquired Immunodeficiency Syndrome AIDS-Related Complex |
Stavudine HIV Protease Inhibitors AIDS Vaccines Ritonavir Reverse Transcriptase Inhibitors HIV Therapeutic Vaccine |
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HIV Infections Blood-Borne Infections Communicable Diseases Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Genital Diseases Urogenital Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir |
Stavudine Didanosine HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antimetabolites Reverse Transcriptase Inhibitors |