Atypical Mycobacterium InfectionPhase 1NCT00001911
Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections
A Phase 1 study testing Interleukin-12 in people with Atypical Mycobacterium Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will test the safety and effectiveness of a drug called interleukin-12 (IL-12) in fighting severe infectious (other than tuberculosis) caused by a group of bacteria called mycobacteria. IL-12 is similar to a substance the body produces naturally to strengthen immune function (infection-fighting ability). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Atypical Mycobacterium Infection
- What is being tested?
- Interleukin-12
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1999to Jul 2003
- 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
Severe disseminated or pulmonary nontuberculous mycobacterial infection refractory to the best tolerated conventional therapy in addition to IFN gamma delivered for at least 3 months. This infection must have been proven by culture at some point during the illness. At the time of enrollment, patients will be eligible if they have negative cultures but histopathologic, examinable, or radiographic evidence of ongoing infection.
In vitro responsiveness to IL-12 as demonstrated by augmentation of peripheral blood mononuclear cell (PBMC) phytohemagglutinin (PHA) induced IFN gamma production.
Women of childbearing age must have a negative pregnancy test (urine or serum) at the time of starting the study and agree to take measures to avoid pregnancy throughout the study while receiving IL-12. Males will be advised that the effects of IL-12 on sperm are not well-known, and they should avoid conception during the study period.
Age 18 years or over.
Adequate hematopoietic, renal and hepatic function, defined as:
Absolute neutrophil count greater than or equal to 1000/microL (G-CSF permitted);
Hemoglobin greater than or equal to 9 g/dl (transfusion or erythropoietin permitted);
Platelet count greater than or equal to 100,000/microL;
Creatinine less than or equal to 1.5 X upper limit of normal;
Bilirubin less than or equal to 1.5 X upper limit of normal;
AST/SGOT less than or equal to 2.5 X upper limit of normal;
ALT/SGPT less than or equal to 2.5 X upper limit of normal;
Calculated Creatinine Clearance greater than 60 mL/min.
Karnofsky Performance Status index greater than or equal to 70.
Written signed informed consent.
No HIV infection.
No active malignancy.
No symptomatic cardiac disease or ongoing treatment for same.
No active seizure disorder or ongoing treatment for same.
No pregnancy or lactation.
No surgery during the two weeks prior to the start of IL-12.
No concurrent use of systematic corticosteroids, except for physiologic replacement.
No exposure to any investigational drug within four weeks prior to the start of dosing.
No gastrointestinal bleeding or uncontrolled peptic ulcer disease.
No history of inflammatory bowel disease or autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus.
No other major illness which, in the investigator's judgement, will substantially increase the risk associated with the patient's participation in this study.
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
This study will test the safety and effectiveness of a drug called interleukin-12 (IL-12) in fighting severe infectious (other than tuberculosis) caused by a group of bacteria called mycobacteria. IL-12 is similar to a substance the body produces naturally to strengthen immune function (infection-fighting ability). It works by stimulating white blood cells to increase production of a chemical called interferon gamma, which can improve or cure mycobacterial infections in some patients.
In previous studies, IL-12 has improved immune function against mycobacteria in test tube experiments and in mice. A recent study of three patients with mycobacterial infections treated with the drug showed encouraging results. The drug has also been studied more extensively in patients with cancer, HIV infection and hepatitis C.
Read more
Patients in this study will receive IL-12 injections under the skin twice a week for one year. They will be taught how to self-administer the drug, but a home care nurse or a physician may also give the injections. The drug dosage will be increased each week to determine the safest and most effective dose for fighting this infection. If intolerable side effects develop at a certain dose, the previous dose level will be used for the next injection. That dose will then be used for the rest of the study, unless unacceptable side effects develop at that level, in which case the dose will again be lowered. Patients will receive an antibiotic against mycobacteria.
Physical examinations and blood and urine tests will be done once a month for at least the first year and then every 3 months the following year to evaluate kidney, liver, and immune function. The first evaluation-at the start of the study-is done on an inpatient basis.
Read the detailed description
Severe nontuberculous mycobacterial infections in patients who are not infected with HIV have been shown to be due to abnormalities in the pathways that generate or use interferon gamma (IFN gamma). In some of these patients treatment with IFN gamma has been effective in improving or curing these infections. Recently, interleukin-12 (IL-12) has been shown to be a potent inducer of IFN gamma along with other cytokines. Experiments in animals and preliminary experience by us in humans suggests that IL-12 may be an important adjunct to antimycobacterial therapy. We seek to use IL-12 in a phase I/II trial in the treatment of severe nontuberculous mycobacterial infections in patients who have not been cured by the best tolerated conventional therapy with IFN gamma. Patients will be studied for inborn or acquired immune defects as well as IL-12 responsiveness in vitro under protocol 93-I-0119 "Detection and Characterization of Host Defense Defects". Patients will receive IL-12 subcutaneously 2 times weekly. We will use an intrapatient dose escalation protocol ranging from 20 ng/kg to 300 ng/kg, depending on the highest dose tolerated by the patient. We expect this study to yield valuable information about tolerance and toxicity. We seek to treat 10 patients over the next 3 years.
- Conditions
- Atypical Mycobacterium Infection
- Being tested
- Interleukin-12
- Keywords
- Cytokine, Interferon Gamma, Pulmonary, Disseminated, Refractory, Mycobacterial Infection, Nontuberculosis Mycobacterial Infection, Pulmonary Nontuberculous Mycobacterial Infection
- Medical subject headings
- Mycobacterium Infections, Nontuberculous, Mycobacterium Infections
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 posted4 Nov 1999 (estimated)
- Study startJul 1999
- Study completionJul 2003
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 Atypical Mycobacterium InfectionStudies 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
- 10 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001911
- Sponsor's protocol ID
- 990147
- Other IDs
- 99-I-0147
- Status last verified
- Jul 2003
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998 May 29;280(5368):1432-5. doi: 10.1126/science.280.5368.1432.
PubMed 9603732Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova JL, Kumararatne DS. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest. 1998 Dec 15;102(12):2035-40. doi: 10.1172/JCI4950.
PubMed 9854038Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M, Young HA, Wolf SF, Young D, Clark SC, Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869-79. doi: 10.1084/jem.173.4.869.
PubMed 1672545
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
- Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections
- ClinicalTrials.gov ID
- NCT00001911
- Acronym / sponsor ID
- 990147
- Conditions
- Atypical Mycobacterium Infection
- Keywords
- Cytokine, Interferon Gamma, Pulmonary, Disseminated, Refractory, Mycobacterial Infection, Nontuberculosis Mycobacterial Infection, Pulmonary Nontuberculous Mycobacterial Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jul 1999
- Study completion
- Jul 2003
- First posted
- 4 Nov 1999 (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.
This study will test the safety and effectiveness of a drug called interleukin-12 (IL-12) in fighting severe infectious (other than tuberculosis) caused by a group of bacteria called mycobacteria. IL-12 is similar to a substance the body produces naturally to strengthen immune function (infection-fighting ability). It works by stimulating white blood cells to increase production of a chemical called interferon gamma, which can improve or cure mycobacterial infections in some patients.
In previous studies, IL-12 has improved immune function against mycobacteria in test tube experiments and in mice. A recent study of three patients with mycobacterial infections treated with the drug showed encouraging results. The drug has also been studied more extensively in patients with cancer, HIV infection and hepatitis C.
Patients in this study will receive IL-12 injections under the skin twice a week for one year. They will be taught how to self-administer the drug, but a home care nurse or a physician may also give the injections. The drug dosage will be increased each week to determine the safest and most effective dose for fighting this infection. If intolerable side effects develop at a certain dose, the previous dose level will be used for the next injection. That dose will then be used for the rest of the study, unless unacceptable side effects develop at that level, in which case the dose will again be lowered. Patients will receive an antibiotic against mycobacteria.
Physical examinations and blood and urine tests will be done once a month for at least the first year and then every 3 months the following year to evaluate kidney, liver, and immune function. The first evaluation-at the start of the study-is done on an inpatient basis.
Detailed description
Severe nontuberculous mycobacterial infections in patients who are not infected with HIV have been shown to be due to abnormalities in the pathways that generate or use interferon gamma (IFN gamma). In some of these patients treatment with IFN gamma has been effective in improving or curing these infections. Recently, interleukin-12 (IL-12) has been shown to be a potent inducer of IFN gamma along with other cytokines. Experiments in animals and preliminary experience by us in humans suggests that IL-12 may be an important adjunct to antimycobacterial therapy. We seek to use IL-12 in a phase I/II trial in the treatment of severe nontuberculous mycobacterial infections in patients who have not been cured by the best tolerated conventional therapy with IFN gamma. Patients will be studied for inborn or acquired immune defects as well as IL-12 responsiveness in vitro under protocol 93-I-0119 "Detection and Characterization of Host Defense Defects". Patients will receive IL-12 subcutaneously 2 times weekly. We will use an intrapatient dose escalation protocol ranging from 20 ng/kg to 300 ng/kg, depending on the highest dose tolerated by the patient. We expect this study to yield valuable information about tolerance and toxicity. We seek to treat 10 patients over the next 3 years.
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 9603732Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, Drysdale P, Jouanguy E, Doffinger R, Bernaudin F, Jeppsson O, Gollob JA, Meinl E, Segal AW, Fischer A, Kumararatne D, Casanova JL. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998 May 29;280(5368):1432-5. doi: 10.1126/science.280.5368.1432.
- Background: PubMed 9854038Altare F, Lammas D, Revy P, Jouanguy E, Doffinger R, Lamhamedi S, Drysdale P, Scheel-Toellner D, Girdlestone J, Darbyshire P, Wadhwa M, Dockrell H, Salmon M, Fischer A, Durandy A, Casanova JL, Kumararatne DS. Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest. 1998 Dec 15;102(12):2035-40. doi: 10.1172/JCI4950.
- Background: PubMed 1672545Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M, Young HA, Wolf SF, Young D, Clark SC, Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869-79. doi: 10.1084/jem.173.4.869.
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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 Atypical Mycobacterium 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 NCT00001911, 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.