Wegener's GranulomatosisPhase 2NCT00040248
Daclizumab to Treat Wegener's Granulomatosis
A Phase 2 study testing Daclizumab in people with Wegener's Granulomatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of daclizumab (also called Zenapax or anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Wegener's Granulomatosis
- What is being tested?
- Daclizumab
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2002to May 2005
- Phase
- Phase 2
- 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
Who may be able to join
- Documentation of WG based on clinical characteristics and histopathologic and/or angiographic evidence of vasculitis. In the absence of histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the following criteria and in whom infectious and autoimmune diseases that may mimic WG have been excluded will also be eligible:
- A positive assay for anti-proteinase 3 or anti-myeloperoxidase autoantibodies (ANCA) and the presence of glomerulonephritis defined by red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of immune deposits.
- A positive assay for anti-proteinase 3 or anti-myeloperoxidase autoantibodies and at least 2 of the following: the presence of granulomatous inflammation on biopsy; abnormal chest radiograph (defined as the presence of nodules, fixed infiltrates, or cavities); nasal/oral inflammation on clinical examination.
- Age 18-75 years.
- Evidence of active disease or if begun on cyclophosphamide (CYC) and glucocorticoids at an outside institution, a history of a active disease at the time of therapy initiation.
- Willingness to travel to the NIH every 2-4 weeks if they are randomized to receive daclizumab.
- Willingness of both women and men to use an effective means of birth control while receiving treatment through this study.
Who cannot join
- Evidence of active infection which, in the judgement of the investigator, is of greater danger to the patient than the underlying vasculitis.
- Patients who are pregnant or who are nursing infants will not be eligible. Women of childbearing potential must have a negative pregnancy test within one week prior to study entry.
- Serological evidence of infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen. A serological determination will be performed within two weeks of beginning study participation.
- Acute or chronic liver disease, past history of alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week), ongoing alcohol use of any volume that cannot be discontinued upon entry into the study.
- History of CYC- or methotrexate-induced pneumonitis or other hypersensitivity reactions to these drugs with past treatment.
- History of transitional cell carcinoma (TCC) of the bladder.
Show all 10Show fewer
- History of any malignant neoplasm except in situ anogenital carcinoma, adequately treated basal or squamous cell carcinoma of the skin, or solid tumors (other than TCC of the bladder cancer) treated with curative therapy and disease free for at least 5 years.
- Inability to comply with study guidelines.
- Hemocytopenia: platelet count less than 80,000/mm(3), absolute neutrophil count less than 1500/mm(3), hematocrit less than 20% (in the absence of gastrointestinal bleeding or hemolytic anemia).
- Known allergy to murine proteins.
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
Official title: A Randomized Trial Examining the Use of Daclizumab in Wegener's Granulomatosis
This study will examine the safety and effectiveness of daclizumab (also called Zenapax or anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis can affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Standard treatment is a combination of prednisone and a cytotoxic agent (a drug that interferes with cell growth), usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will focus on the effectiveness of daclizumab in preventing disease relapse.
The Food and Drug Administration approved daclizumab in 1997 for preventing kidney transplant rejection, and the drug has also been studied in people with an eye infection called uveitis. The drug works by binding to a protein on T lymphocytes (white blood cells of the immune system) called CD25. This prevents another protein, called interleukin-2, from binding to this site, thereby preventing a series of events that normally results in inflammation.
Read more
Patients between 10 and 75 years of age with Wegener's granulomatosis may be eligible for this study.
Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, x-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be conducted. All patients will begin treatment with prednisone and cyclophosphamide daily. Those who improve on this regimen will reduce the prednisone gradually and continue with cyclophosphamide until their disease is in remission. While taking cyclophosphamide, patients must have blood and urine tests done every 1 to 2 weeks. Those who achieve disease remission will stop cyclophosphamide and start taking methotrexate once a week, usually by mouth but possibly by injection into the muscle or skin. Blood and urine tests will be conducted once a week for 4 weeks while the dosage is being adjusted and then once a month for the duration of treatment. Patients on methotrexate whose prednisone dose is reduced to 10 to 30 mg every other day will be randomly assigned either to receive or not receive daclizumab in addition to the methotrexate. Daclizumab is given intravenously (through a plastic tube inserted into a vein) the day after the randomization, then again in 2 weeks, 4 weeks, and once a month for 18 months.
All patients will continue to taper their prednisone dose until it is stopped. Methotrexate will continue for 2 years. Patients whose disease remains in remission at this time will decrease the methotrexate dose. If there is no active disease when both prednisone and methotrexate have been stopped, no further treatment will be given. If disease recurs at a later time, treatment will be reinstituted. The treatment will be determined by the severity of disease, other medical conditions, and history of side effects. Patients not randomized to daclizumab who relapse while still taking methotrexate may be offered re-treatment with daclizumab.
Patients will be evaluated in the outpatient clinic every 4 to 8 weeks until randomization. Patients not taking daclizumab will be followed every 4 to 12 weeks; those taking the drug will be seen every 2 weeks for the first month, every month after that during the 18-month treatment period, and every 4 to 12 weeks until all medications stop. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.
Read the detailed description
The purpose of this study is to assess the safety and efficacy of daclizumab as an adjunctive treatment to methotrexate in maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will receive methotrexate for remission maintenance. Following the switch to methotrexate and when the prednisone dose has been tapered to 20mg QOD (plus or minus 10mg QOD), patients in remission will be randomized to receive daclizumab or not receive daclizumab. Those randomized to receive daclizumab will be treated with 1 mg/kg intravenously on day 0, week 2, week 4 and every month thereafter for a total of 18 months (20 doses). Regardless to which arm the patient is randomized, they will continue to receive methotrexate. Two years after the methotrexate was started, if the patient remains in remission, this will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events.
- Conditions
- Wegener's Granulomatosis
- Being tested
- Daclizumab
- Keywords
- Relapse, Monoclonal Antibody, Biologic Agent, Anti-CD25, Activated Lymphocyte, Wegener Granulomatosis, Wegener's Granulomatosis, WG
- Medical subject headings
- Granulomatosis with Polyangiitis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2002 (estimated)
- Study startJun 2002
- Study completionMay 2005
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 Wegener's GranulomatosisStudies 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 2
- Primary purpose
- Treatment
- Enrolment
- 75 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00040248
- Sponsor's protocol ID
- 020213
- Other IDs
- 02-I-0213
- Status last verified
- May 2005
- First submitted
- 22 Jun 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert H, Nolle B, Heller M, Gross WL. An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients. Arthritis Rheum. 2000 May;43(5):1021-32. doi: 10.1002/1529-0131(200005)43:53.0.CO;2-J.
PubMed 10817555Stone JH, Tun W, Hellman DB. Treatment of non-life threatening Wegener's granulomatosis with methotrexate and daily prednisone as the initial therapy of choice. J Rheumatol. 1999 May;26(5):1134-9.
PubMed 10332980de Groot K, Muhler M, Reinhold-Keller E, Paulsen J, Gross WL. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol. 1998 Mar;25(3):492-5.
PubMed 9517769
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
- A Randomized Trial Examining the Use of Daclizumab in Wegener's Granulomatosis
- ClinicalTrials.gov ID
- NCT00040248
- Acronym / sponsor ID
- 020213
- Conditions
- Wegener's Granulomatosis
- Keywords
- Relapse, Monoclonal Antibody, Biologic Agent, Anti-CD25, Activated Lymphocyte, Wegener Granulomatosis, Wegener's Granulomatosis, WG
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jun 2002
- Study completion
- May 2005
- First posted
- 24 Jun 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.
This study will examine the safety and effectiveness of daclizumab (also called Zenapax or anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis can affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Standard treatment is a combination of prednisone and a cytotoxic agent (a drug that interferes with cell growth), usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will focus on the effectiveness of daclizumab in preventing disease relapse.
The Food and Drug Administration approved daclizumab in 1997 for preventing kidney transplant rejection, and the drug has also been studied in people with an eye infection called uveitis. The drug works by binding to a protein on T lymphocytes (white blood cells of the immune system) called CD25. This prevents another protein, called interleukin-2, from binding to this site, thereby preventing a series of events that normally results in inflammation.
Patients between 10 and 75 years of age with Wegener's granulomatosis may be eligible for this study.
Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, x-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be conducted. All patients will begin treatment with prednisone and cyclophosphamide daily. Those who improve on this regimen will reduce the prednisone gradually and continue with cyclophosphamide until their disease is in remission. While taking cyclophosphamide, patients must have blood and urine tests done every 1 to 2 weeks. Those who achieve disease remission will stop cyclophosphamide and start taking methotrexate once a week, usually by mouth but possibly by injection into the muscle or skin. Blood and urine tests will be conducted once a week for 4 weeks while the dosage is being adjusted and then once a month for the duration of treatment. Patients on methotrexate whose prednisone dose is reduced to 10 to 30 mg every other day will be randomly assigned either to receive or not receive daclizumab in addition to the methotrexate. Daclizumab is given intravenously (through a plastic tube inserted into a vein) the day after the randomization, then again in 2 weeks, 4 weeks, and once a month for 18 months.
All patients will continue to taper their prednisone dose until it is stopped. Methotrexate will continue for 2 years. Patients whose disease remains in remission at this time will decrease the methotrexate dose. If there is no active disease when both prednisone and methotrexate have been stopped, no further treatment will be given. If disease recurs at a later time, treatment will be reinstituted. The treatment will be determined by the severity of disease, other medical conditions, and history of side effects. Patients not randomized to daclizumab who relapse while still taking methotrexate may be offered re-treatment with daclizumab.
Patients will be evaluated in the outpatient clinic every 4 to 8 weeks until randomization. Patients not taking daclizumab will be followed every 4 to 12 weeks; those taking the drug will be seen every 2 weeks for the first month, every month after that during the 18-month treatment period, and every 4 to 12 weeks until all medications stop. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.
Detailed description
The purpose of this study is to assess the safety and efficacy of daclizumab as an adjunctive treatment to methotrexate in maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will receive methotrexate for remission maintenance. Following the switch to methotrexate and when the prednisone dose has been tapered to 20mg QOD (plus or minus 10mg QOD), patients in remission will be randomized to receive daclizumab or not receive daclizumab. Those randomized to receive daclizumab will be treated with 1 mg/kg intravenously on day 0, week 2, week 4 and every month thereafter for a total of 18 months (20 doses). Regardless to which arm the patient is randomized, they will continue to receive methotrexate. Two years after the methotrexate was started, if the patient remains in remission, this will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Documentation of WG based on clinical characteristics and histopathologic and/or angiographic evidence of vasculitis. In the absence of histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the following criteria and in whom infectious and autoimmune diseases that may mimic WG have been excluded will also be eligible:
- A positive assay for anti-proteinase 3 or anti-myeloperoxidase autoantibodies (ANCA) and the presence of glomerulonephritis defined by red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of immune deposits.
- A positive assay for anti-proteinase 3 or anti-myeloperoxidase autoantibodies and at least 2 of the following: the presence of granulomatous inflammation on biopsy; abnormal chest radiograph (defined as the presence of nodules, fixed infiltrates, or cavities); nasal/oral inflammation on clinical examination.
- Age 18-75 years.
- Evidence of active disease or if begun on cyclophosphamide (CYC) and glucocorticoids at an outside institution, a history of a active disease at the time of therapy initiation.
Key exclusion criteria (10 listed)
- Evidence of active infection which, in the judgement of the investigator, is of greater danger to the patient than the underlying vasculitis.
- Patients who are pregnant or who are nursing infants will not be eligible. Women of childbearing potential must have a negative pregnancy test within one week prior to study entry.
- Serological evidence of infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen. A serological determination will be performed within two weeks of beginning study participation.
- Acute or chronic liver disease, past history of alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week), ongoing alcohol use of any volume that cannot be discontinued upon entry into the study.
- History of CYC- or methotrexate-induced pneumonitis or other hypersensitivity reactions to these drugs with past treatment.
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 |
|---|---|---|
| Daclizumab | 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 10817555Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert H, Nolle B, Heller M, Gross WL. An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in 155 patients. Arthritis Rheum. 2000 May;43(5):1021-32. doi: 10.1002/1529-0131(200005)43:53.0.CO;2-J.
- Background: PubMed 10332980Stone JH, Tun W, Hellman DB. Treatment of non-life threatening Wegener's granulomatosis with methotrexate and daily prednisone as the initial therapy of choice. J Rheumatol. 1999 May;26(5):1134-9.
- Background: PubMed 9517769de Groot K, Muhler M, Reinhold-Keller E, Paulsen J, Gross WL. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol. 1998 Mar;25(3):492-5.
Related trials for Wegener's Granulomatosis
RecruitingPhase 3
A Trial to Investigate Benralizumab in Children With Eosinophilic Diseases
Eosinophilic Granulomatosis With Polyangiitis (EGPA), Hypereosinophilia Syndrome (HES)
RecruitingPhase 3
Roll-over Study for Participants Who Have Completed a Previous Clinical Study With Benralizumab (Fasenra) and Benefit From Continued Treatment
Asthma, Eosinophilic Granulomatosis With Polyangiitis (EGPA)
Active, not recruitingPhase 1/2
An Open-label Study of Povetacicept in Autoantibody-Associated Glomerular Diseases
Lupus Nephritis, Immunoglobulin A Nephropathy
Active, not recruitingPhase 2
Iptacopan in Patients With ANCA Associated Vasculitis
Anti-Neutrophil Cytoplasm Antibodies (ANCA) Associated Vasculitis
Active, not recruitingPhase 1/2
TEMPO Study: Trimethoprim-Sulfamethoxazole in Granulomatosis With Polyangiitis
Granulomatosis With Polyangiitis, Wegener Granulomatosis
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 2 study testing Daclizumab in people with Wegener's Granulomatosis, 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.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 NCT00040248, 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.