Acquired Immunodeficiency SyndromePhase 1NCT00001763
Subcutaneously Administered Interleukin-12 Therapy in HIV-Infected Patients With Disseminated Mycobacterium Avium Complex Infection
A Phase 1 study testing Interleukin-12 in people with Acquired Immunodeficiency Syndrome and Mycobacterium Avium-Intracellulare Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acquired Immunodeficiency Syndrome, Mycobacterium Avium-Intracellulare Infection
- What is being tested?
- Interleukin-12
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 1998to Mar 2000
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Documented HIV infection (ELISA and Western blot positive).
18 years or older.
Clinically stable enough to travel to NIH and meet protocol schedule requirements.
Negative urine or serum pregnancy test within 14 days prior to study entry (for women of childbearing potential).
Patients should be receiving a combination of FDA approved antiretroviral drugs or expanded access antiretroviral therapy for at least two weeks prior to study entry. The exception would be that, in the opinion of the primary treating physician, this therapy would not likely provide benefit.
Greater than or equal to 1 positive blood culture or 1 positive culture from a normally sterile site (e.g. lymph node, bone marrow, etc.) for MAC within 6 weeks of study. The initial screening blood culture at the NIH must be positive.
The following lab values must be present at study entry:
Transaminases, alkaline phosphatase, total bilirubin less than or equal to 5x upper limit of normal range.
Serum creatinine less than or equal to 2.0 mg/ml.
Proteinuria less than or equal to positive 1.
Normal PT/PTT.
Granulocyte count greater than or equal to 750/cubic millimeter.
Hemoglobin greater than or equal to 8 gm/dL and platelet count greater than or equal to 75,000.
Fasting Blood glucose 1.25x upper normal limit (126 g/dl). (In persons with no history of diabetes.)
No malignancy other than Kaposi sarcoma. Patients with Kaposi sarcoma are eligible, but must not have received systemic therapy for KS.
No current life threatening AIDS related opportunistic infection other than disseminated MAC.
No evidence of active substance abuse according to the standard 8th floor clinic substance abuse assessment, which allows enrollment at the discretion of the principal investigator.
No patients exhibiting psychiatric disturbance or illness, which in the assessment of the protocol team may affect patient safety or compliance.
No significant cardiac, gastrointestinal, pulmonary, autoimmune, renal, or CNS disease which could interfere with patient safety.
No hypertension requiring anti-hypertensive therapy.
No pregnant or lactating patients, or any patient with an inability or unwillingness to use effective contraception.
Willingness to comply with current NIH Clinical Center guidelines concerning appropriate notification by an individual of current or ongoing sexual partners and/or needle-sharing partners regarding his or her HIV seropositivity and the risk of transmission of HIV infection.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
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.
Read the detailed 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.
- Being tested
- Interleukin-12
- Keywords
- AIDS, Cell Mediated Immunity, Cytokine, MAC, Thl Response
- Medical subject headings
- Acquired Immunodeficiency Syndrome, Mycobacterium avium-intracellulare Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-12Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startApr 1998
- Study completionMar 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 15 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001763
- Sponsor's protocol ID
- 980091
- Other IDs
- 98-I-0091
- Status last verified
- Apr 1999
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Bermudez LE, Martinelli J, Petrofsky M, Kolonoski P, Young LS. Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model. J Infect Dis. 1994 Mar;169(3):575-80. doi: 10.1093/infdis/169.3.575.
PubMed 8158029Chaisson RE, Benson CA, Dube MP, Heifets LB, Korvick JA, Elkin S, Smith T, Craft JC, Sattler FR. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med. 1994 Dec 15;121(12):905-11. doi: 10.7326/0003-4819-121-12-199412150-00001.
PubMed 7978715Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, Benson CA, Meek K, Siepman N, Craft JC. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS. 1997 Mar;11(3):311-7. doi: 10.1097/00002030-199703110-00008.
PubMed 9147422
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subcutaneously Administered Interleukin-12 Therapy in HIV-Infected Patients With Disseminated Mycobacterium Avium Complex Infection
- ClinicalTrials.gov ID
- NCT00001763
- Acronym / sponsor ID
- 980091
- Keywords
- AIDS, Cell Mediated Immunity, Cytokine, MAC, Thl Response
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Apr 1998
- Study completion
- Mar 2000
- First posted
- 10 Dec 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interleukin-12 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8158029Bermudez LE, Martinelli J, Petrofsky M, Kolonoski P, Young LS. Recombinant granulocyte-macrophage colony-stimulating factor enhances the effects of antibiotics against Mycobacterium avium complex infection in the beige mouse model. J Infect Dis. 1994 Mar;169(3):575-80. doi: 10.1093/infdis/169.3.575.
- Background: PubMed 7978715Chaisson RE, Benson CA, Dube MP, Heifets LB, Korvick JA, Elkin S, Smith T, Craft JC, Sattler FR. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med. 1994 Dec 15;121(12):905-11. doi: 10.7326/0003-4819-121-12-199412150-00001.
- Background: PubMed 9147422Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, Benson CA, Meek K, Siepman N, Craft JC. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS. 1997 Mar;11(3):311-7. doi: 10.1097/00002030-199703110-00008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Interleukin-12 in people with Acquired Immunodeficiency Syndrome and Mycobacterium Avium-Intracellulare Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001763, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.