Clinical Trials Logo

Clinical Trial Summary

Disseminated infection with Mycobacteria avium complex (MAC) is one of the most common systemic bacterial infections in advanced stages of the acquired immunodeficiency syndrome (AIDS). Current therapy for disseminated MAC infection in HIV patients consists of multidrug chemotherapy regimens are often accompanied by toxicities, and many patients become intolerant of one or more agents. Macrolides are the essential component of successful therapy, yet macrolide resistant strains are being recognized with increasing frequency. Thus, there is an interest in identifying additional therapeutic interventions for disseminated MAC in HIV-infected patients. Interleukin-12 (IL-12) is a central, regulatory cytokine in cell-mediated immunity. IL-12 enhances the cytolytic activity of cytotoxic T and NK cells, and induces interferon-gamma (IFN gamma) production from T and NK cells. This open-label Phase I study is designed to evaluate the safety and immunologic/microbiologic effects of interleukin-12 administration in HIV-infected patients with concomitant disseminated Mycobacterium avium (MAC) infection. Fifteen patients with documented disseminated MAC will be randomized to receive double-blinded placebo or escalating doses of IL-12 in addition to anti-MAC chemotherapy and standard anti-retroviral therapy for six weeks. IL-12 will be administered subcutaneously, with escalating doses every month over the dose range of 30 ng/kg, 100 ng/kg, and 300 ng/kg, or until an individual maximum tolerated dose (IMTD) is reached. Should a patient receive 2 consecutive blood cultures negative for MAC during the course of the study at a lower dose, then he/she will not be further dose escalated. Those patients receiving placebo after 6 weeks will be crossed over to receive the full treatment course of IL-12. Each new dose or dose escalation will take place on an inpatient basis. Once a patient is clinically stable at a dose, the patient will be maintained at that dose as an outpatient for the remainder of the month. Total IL-12 administration will not exceed 12 weeks, or 24 total doses.


Clinical Trial Description

Disseminated infection with Mycobacteria avium complex (MAC) is one of the most common systemic bacterial infections in advanced stages of the acquired immunodeficiency syndrome (AIDS). Current therapy for disseminated MAC infection in HIV patients consists of multidrug chemotherapy regimens are often accompanied by toxicities, and many patients become intolerant of one or more agents. Macrolides are the essential component of successful therapy, yet macrolide resistant strains are being recognized with increasing frequency. Thus, there is an interest in identifying additional therapeutic interventions for disseminated MAC in HIV-infected patients. Interleukin-12 (IL-12) is a central, regulatory cytokine in cell-mediated immunity. IL-12 enhances the cytolytic activity of cytotoxic T and NK cells, and induces interferon-gamma (IFN gamma) production from T and NK cells. This open-label Phase I study is designed to evaluate the safety and immunologic/microbiologic effects of interleukin-12 administration in HIV-infected patients with concomitant disseminated Mycobacterium avium (MAC) infection or localized MAC infection. Fifteen patients with documented disseminated MAC will be randomized to receive double-blinded placebo or escalating doses of IL-12 in addition to anti-MAC chemotherapy and standard anti-retroviral therapy for six weeks. IL-12 will be administered subcutaneously, with escalating doses every month over the dose range of 30 ng/kg, 100 ng/kg, and 300 ng/kg, or until an individual maximum tolerated dose (IMTD) is reached. Should a patient receive 2 consecutive blood cultures negative for MAC during the course of the study at a lower dose, then he/she will not be further dose escalated. Likewise, patients with localized disease will not be further dose escalated if symptoms/evidence of localized infection resolve as assessed by the principal investigator. Those patients receiving placebo after 6 weeks will be crossed over to receive the full treatment course of IL-12. Each new dose or dose escalation will take place on an inpatient basis. Once a patient is clinically stable at a dose, the patient will be maintained at that dose as an outpatient for the remainder of the month. Total IL-12 administration will not exceed 12 weeks, or 24 total doses. ;


Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00001763
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase Phase 1
Start date April 1998
Completion date March 2000

See also
  Status Clinical Trial Phase
Completed NCT01968551 - Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults Phase 3
Completed NCT02929069 - A Unified Intervention for Young Gay and Bisexual Men's Minority Stress, Mental Health, and HIV Risk N/A
Recruiting NCT02392884 - HIV Medication Adherence in Underserved Populations N/A
Completed NCT02583464 - Bioequivalence Study of Two Formulations With the Association of Tenofovir 300 mg and Emtricitabine 200 mg. Phase 1
Completed NCT02264509 - Peripheral Arterial Insufficiency Associated With HIV/AIDS N/A
Completed NCT01440569 - Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults Phase 3
Completed NCT00551330 - Vicriviroc in HIV(R5/X4)-Treatment Experienced Subjects (Study P05057AM5)(COMPLETED) Phase 2
Completed NCT00381212 - A Pilot Study to Investigate the Safety and Immunologic Activity AGS-004 an Autologous HIV Immunotherapeutic Agent. Phase 1/Phase 2
Completed NCT00097006 - Retrovirus Epidemiology Donor Study-II (REDS-II) N/A
Completed NCT00001409 - Genetically Modified Lymphocytes to Treat HIV-Infected Identical Twins - Study Modifications Phase 1
Completed NCT00000590 - Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185) Phase 3
Completed NCT00000587 - Erythropoietin for Anemia Due to Zidovudine in Human Immunodeficiency Virus Infection Phase 2
Completed NCT00005273 - Pulmonary Complications of HIV Infection Study (PACS) N/A
Completed NCT00005303 - Effectiveness of AIDS Antibody Screening N/A
Completed NCT00005301 - Transfusion Safety Study (TSS) N/A
Completed NCT00001650 - Use of Bromodeoxyuridine to Study White Blood Cell Replication and Survival in HIV-Infected Patients N/A
Withdrawn NCT00243568 - Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285 Phase 3
Recruiting NCT05031819 - Managing Hypertension Among People Living With HIV N/A
Completed NCT00394004 - Decision-Making of Hispanics and African-Americans With HIV/AIDS Participating in Clinical Trials N/A
Completed NCT01967940 - Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults Phase 3