Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisPhase 2NCT01275287
Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis - Eculizumab
A Phase 2 study testing eculizumab in people with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
- What is being tested?
- eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to Dec 2012
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria:• Patients with active Antineutrophil Cytoplasmic Autoantibodies (ANCA) glomerulonephritis and/or small vessel vasculitis with de novo or relapsing disease (BVAS≥5).
- Patients must have a current or a history of positive ANCA by the ELISA technique.
- De novo or relapsing disease requiring immunosuppression.
- Patients must have evidence of active glomerulonephritis as evidenced by the presence of glomerular hematuria (dysmorphic Red Blood Cells (RBCs) or RBC casts) with or without an increase in serum creatinine.
- Patients will be eligible within 10 days of commencing induction therapy (i.e., they may have already received pulse methylprednisolone and first dose of cyclophosphamide).
Exclusion Criteria:• Pregnancy or lactation, or women of child bearing potential who are not willing or able to comply with 2 contraceptive methods.
- Patients with severe renal failure: creatinine > 6 mg/dL or receiving hemodialysis and/or receiving plasmapheresis therapy.
- Patients with severe pulmonary hemorrhage requiring ventilation and/or plasmapheresis therapy.
- Patients with active bacterial or viral infection.
- Absolute neutrophils count < 1000/mm^3 to minimize the risk of infections
- Hemoglobin < 8.5 g/dL
- Prior therapy with a monoclonal antibody (for example rituximab)within the previous 6 months. Peripheral CD-20 B-cells count <= 1% due to rituximab even longer than 6 months.
- Severe coexisting conditions precluding immunosuppressive therapy or conditions requiring intravenous antibiotic therapy.
- History of infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV, tuberculosis or syphilis.
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Kidney Center
Chapel Hill, North Carolina, 27510-7155
About this study
Official title: Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis
The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity.
ANCA vasculitis is an inflammation of the small vessels whereby ANCA antibodies inappropriately activate one's own white blood cells (neutrophils) and cause damage to the small blood vessels.
Read the detailed description
Recent laboratory studies have identified that an important pathway of inflammation called the "complement pathway" may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation.
In a mouse model of ANCA vasculitis, it has been shown that blocking C5 activation can block the development of vasculitis or greatly reduce its severity.
The researchers in this study would like to see if taking eculizumab, in addition to the drugs usually used to treat ANCA vasculitis, would be beneficial in treating ANCA vasculitis.
Currently, the conventional treatment of ANCA vasculitis consists of corticosteroids and cyclophosphamide. The corticosteroids are given as by vein (methylprednisolone) for 3 days followed by prednisone by mouth daily for about 4-5 months. Cyclophosphamide is typically given by vein every 4 weeks for at least 3 months, but sometimes longer depending on whether the vasculitis is still active or not. After the vasculitis is in remission, a maintenance treatment with azathioprine or mycophenolate mofetil may be used. For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, patients who need rituximab or have recently been treated with rituximab cannot participate in this study.
The study drug, eculizumab, is Food and Drug Administration (FDA) approved for indications other than ANCA vasculitis. It is an investigational drug and it is NOT FDA-approved for the treatment of ANCA vasculitis.
In this study, eculizumab will be given in addition to the standard of care treatment for the patients that will be randomised to the eculizumab group.
- Being tested
- Standard of care treatment, eculizumab
- Keywords
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Complement Activation
- Medical subject headings
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of care treatmentDrug
Also called cytoxan
induction : pulse methyl prednisolone (7 mg/kg/day x3) then prednisone 1 mg/kg/day (not to exceed 60 mg/day) for 4 weeks, then taper over the following 12 weeks. Cyclophosphamide starting at 0.75 gm/m2 IV (decreased to 0.5 gm/m^2 for patients > than 70 or with estimated Glomerular Filtration Rate (eGFR) < 20 ml/min) to be titrated up to 1 gm/m^2 depending on the 2 week white blood count (WBC) nadir > 3000 cell/μL. Subsequent cyclophosphamide will be given every 4 weeks for at least 2 more doses. Once complete remission for 2 months, patient may be switched from cyclophosphamide to maintenance therapy with azathioprine 1.5-2 mg/kg/day for 6-9 months (to a total of 12 months of therapy) .
For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, if rituximab is indicated for the patient, he cannot participate in the study.
eculizumabDrug
Also called Soliris
In addition to conventional therapy, patients randomized to eculizumab will receive 600 mg by IV infusion over 35 minutes every 7 days for the first 4 weeks, then 900 mg by IV infusion for the fifth dose 7 days later (week 5), then 900 mg every 14 days thereafter, for a total of 9 doses (about 3 months of treatment). This dosing scheme is based on that used for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). The length of treatment is shorter than for PNH, based on a desire to target the addition of eculizumab to the period of maximal disease activity, while limiting the risks of infectious complications in this first pilot study.
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Active comparator | Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here. Receives: Drug: Standard of care treatment |
| Eculizumab arm | Experimental | Standard of care for ANCA vasculitis + eculizumab treatment
Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here. Receives: Drug: eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Birmingham Vasculitis Activity Score (BVAS)
Change in disease activity as measured by BVAS at 12 weeks.
Measured: 12 weeks
Secondary outcomes (6)
Complement levels elevation
Evaluation of complement levels at study entry to determine which may be elevated in active disease (Bb, C3a, C3d, C3d/C3, C4d, C5a or C5b-9
Measured: up to 52 weeks
Birmingham Vasculitis Activity Score(BVAS)
Percent of patients with a BVAS =0 at 3 months
Measured: up to 52 weeks
Normalisation of complement activation
Normalization of complement activation at 4 weeks, 8, 12, 24, 36 and 52 weeks
Measured: up to 52 weeks
Change in complement levels
Change in complement levels between groups from baseline to week 12
Measured: from baseline to week 12
change in complement levels 2
Change in these complement levels with treatment and decrease in disease activity for each patient
Measured: up to 52 weeks
Birmingham Vasculitis Activity Score (BVAS) 2
Mean BVAS at 24, 36 and 52 weeks
Measured: up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: the study failed to enroll any patient and sponsor wished to stop.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc., National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Patrick H Nachman, MD, Principal investigator, UNC Kidney Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01275287
- Sponsor's protocol ID
- 10-2218
- Other IDs
- P01DK058335
- Status last verified
- Sep 2016
- First submitted
- 13 Dec 2010
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: no plan too share data
Publications
Bala MM, Malecka-Massalska TJ, Koperny M, Zajac JF, Jarczewski JD, Szczeklik W. Anti-cytokine targeted therapies for ANCA-associated vasculitis. Cochrane Database Syst Rev. 2020 Sep 29;9(9):CD008333. doi: 10.1002/14651858.CD008333.pub2.
PubMed 32990324
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis
- ClinicalTrials.gov ID
- NCT01275287
- Acronym / sponsor ID
- 10-2218
- Keywords
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Complement Activation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: the study failed to enroll any patient and sponsor wished to stop.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc., National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 12 Jan 2011 (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.
The purpose of this research study is to see if Eculizumab (Soliris®) can safely be used in addition to conventional therapy in patients with active ANCA (Antineutrophil Cytoplasmic Autoantibodies ) vasculitis and lead to a more rapid decrease in disease activity.
ANCA vasculitis is an inflammation of the small vessels whereby ANCA antibodies inappropriately activate one's own white blood cells (neutrophils) and cause damage to the small blood vessels.
Detailed description
Recent laboratory studies have identified that an important pathway of inflammation called the "complement pathway" may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation.
In a mouse model of ANCA vasculitis, it has been shown that blocking C5 activation can block the development of vasculitis or greatly reduce its severity.
The researchers in this study would like to see if taking eculizumab, in addition to the drugs usually used to treat ANCA vasculitis, would be beneficial in treating ANCA vasculitis.
Currently, the conventional treatment of ANCA vasculitis consists of corticosteroids and cyclophosphamide. The corticosteroids are given as by vein (methylprednisolone) for 3 days followed by prednisone by mouth daily for about 4-5 months. Cyclophosphamide is typically given by vein every 4 weeks for at least 3 months, but sometimes longer depending on whether the vasculitis is still active or not. After the vasculitis is in remission, a maintenance treatment with azathioprine or mycophenolate mofetil may be used. For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, patients who need rituximab or have recently been treated with rituximab cannot participate in this study.
The study drug, eculizumab, is Food and Drug Administration (FDA) approved for indications other than ANCA vasculitis. It is an investigational drug and it is NOT FDA-approved for the treatment of ANCA vasculitis.
In this study, eculizumab will be given in addition to the standard of care treatment for the patients that will be randomised to the eculizumab group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Active comparator | Drug: Standard of care treatmentStandard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here. |
| Eculizumab arm | Experimental | Drug: eculizumabStandard of care for ANCA vasculitis + eculizumab treatment Standard of care for ANCA vasculitis treatment- depends on severity of disease and individual characteristics and medical history of each patient so this won't be described here. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 |
|---|---|---|
| Standard of care treatmentAlso: cytoxaninduction : pulse methyl prednisolone (7 mg/kg/day x3) then prednisone 1 mg/kg/day (not to exceed 60 mg/day) for 4 weeks, then taper over the following 12 weeks. Cyclophosphamide starting at 0.75 gm/m2 IV (decreased to 0.5 gm/m^2 for patients > than 70 or with estimated Glomerular Filtration Rate (eGFR) < 20 ml/min) to be titrated up to 1 gm/m^2 depending on the 2 week white blood count (WBC) nadir > 3000 cell/μL. Subsequent cyclophosphamide will be given every 4 weeks for at least 2 more doses. Once complete remission for 2 months, patient may be switched from cyclophosphamide to maintenance therapy with azathioprine 1.5-2 mg/kg/day for 6-9 months (to a total of 12 months of therapy) . For patients who cannot tolerate cyclophosphamide, or who have received it in large doses previously, another medication called rituximab may be used instead. However, if rituximab is indicated for the patient, he cannot participate in the study. | Drug | Standard of care |
| eculizumabAlso: SolirisIn addition to conventional therapy, patients randomized to eculizumab will receive 600 mg by IV infusion over 35 minutes every 7 days for the first 4 weeks, then 900 mg by IV infusion for the fifth dose 7 days later (week 5), then 900 mg every 14 days thereafter, for a total of 9 doses (about 3 months of treatment). This dosing scheme is based on that used for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH). The length of treatment is shorter than for PNH, based on a desire to target the addition of eculizumab to the period of maximal disease activity, while limiting the risks of infectious complications in this first pilot study. | Drug | Eculizumab arm |
Primary outcome
Birmingham Vasculitis Activity Score (BVAS)
Time frame: 12 weeks
Change in disease activity as measured by BVAS at 12 weeks.
6 secondary outcomes
Complement levels elevation
Time frame: up to 52 weeks
Birmingham Vasculitis Activity Score(BVAS)
Time frame: up to 52 weeks
Normalisation of complement activation
Time frame: up to 52 weeks
Change in complement levels
Time frame: from baseline to week 12
change in complement levels 2
Time frame: up to 52 weeks
Birmingham Vasculitis Activity Score (BVAS) 2
Time frame: up to 52 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Derived from this study: PubMed 32990324Bala MM, Malecka-Massalska TJ, Koperny M, Zajac JF, Jarczewski JD, Szczeklik W. Anti-cytokine targeted therapies for ANCA-associated vasculitis. Cochrane Database Syst Rev. 2020 Sep 29;9(9):CD008333. doi: 10.1002/14651858.CD008333.pub2.
- Individual participant dataSharing planned: No. no plan too share data
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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.
Patrick H Nachman, MD principal investigator
UNC Kidney Center
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 eculizumab in people with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by University of North Carolina, Chapel Hill 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?
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: withdrawn, as of the sponsor's last update on 23 Feb 2017. 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 was withdrawn before enrolling participants, so there are no results.
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.
What does the primary outcome measure?
Birmingham Vasculitis Activity Score (BVAS) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01275287, which also lists 1 linked publication.
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 23 Feb 2017.