Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisPhase 4MAINTANCAVASNCT02749292

Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing

A Phase 4 study testing Rituximab in people with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by Massachusetts General Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 82 years
Conditions the study is for: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
What is being tested?: Rituximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 115 participants
Where: 1 siteUnited States
Study dates: Jun 2016to 31 Jan 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 82 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

All patients must be able and willing to give written informed consent and comply with the requirements of the study protocol.
Diagnosis: ANCA vasculitis as defined by a positive MPO- and/or PR3-ANCA test together with clinical features characteristic of ANCA-positive diseases as detailed in the 2012 Chapel Hill Consensus Conference Definitions(18).
eGFR ≥ 73 cc/min/1.73m2
Age: 18-82 years old
Treated with rituximab-induced continuous B cell depletion at regularly scheduled interval with a goal of undetectable B cells for at least 24 months
In sustained remission (defined by a modified BVAS-WG=0 AND a prednisone dose of ≤ 7.5 mg) for at least 12 months.

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Undetectable (<10mm3) B cells (quantified by CD20+ number) on day 0
Urine Hcg negative for women of child bearing potential and not planning to become pregnant for at least 12 months from enrollment and at least 12 months after any study related rituximab dose
Judged to be otherwise healthy by the Investigator, based on medical history and physical examination (no known active disease process for which life expectancy is less than 36 months)

Who cannot join

Secondary Disease: disease suspected to be induced by levamisole-adulterated cocaine
All transplanted patients
Treatment: additional immunosuppressive agents other than rituximab and/or total daily prednisone dose ≥ 7.5 milligrams
Hypogammaglobulinemia: IgG level < 300 mg/dL
Terminal cancer or other primary illness with life expectancy of less than 36 months
Active anti-GBM disease and other known autoimmune disease for which the need for additional immunosuppression is likely
Pregnancy or breastfeeding

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing Based on B-cell Reconstitution vs a Serologic ANCA Flare

The purpose of this study is to determine the best management strategy to maintain remission in patients with ANCA vasculitis who have been treated with rituximab induced B cell depletion for at least two years. This study will compare intermittent B Cell depletion upon B cell return or intermittent B cell depletion upon serologic relapse.

Read the detailed description

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a systemic autoimmune disease characterized by small vessel inflammation caused by pathogenic autoantibodies directed against proteinase 3 (PR3) or myeloperoxidase (MPO). Immunosuppressive therapy can result in remission; however, many patients relapse, which results in additional injury.

Rituximab, a humanized murine monoclonal antibody directed against CD20 located on the surface of B-lymphocytes (B cells), is effective in depleting B cells. The RAVE and RITUXVAS trials have shown efficacy of rituximab with steroids for induction of remission in ANCA vasculitis, similar to cyclophosphamide and steroids. Rituximab is now FDA-approved for induction of remission therapy in ANCA vasculitis. The utility of anti-B-cell therapy for early induction of remission in ANCA vasculitis is not surprising given that ANCA are pathogenic in vitro and in vivo. It is clear that remission in many patients is not sustained with a single induction course of rituximab, and relapses often occur after B cell re-population suggesting that scheduled, serial dosing of rituximab could result in sustained remissions.

Despite yielding promising outcomes, rituximab is also associated with a number of adverse events including infectious complications and late onset of neutropenia5, 15. Furthermore, the complications of continuous B cell depletion for extended durations are unknown. One of the major goals in the field is to utilize prolonged B cell depletion only in the subpopulation of patients where the risk of disease relapse outweighs the risk of treatment-related adverse events.

A rise in ANCA titers and reconstitution of B cells are promising biomarkers of impending disease relapse following treatment with rituximab4-6

A prospective and longitudinal clinical trial is needed to determine the ideal treatment strategy for long-term maintenance of remission. We propose to compare intermittent rituximab dosing based on B cell return and a serologic ANCA flare

The study design is an open-label, single center, randomized and two-arm controlled trial to evaluate the optimal maintenance of remission strategy that provides the best relapse-free survival in patients with ANCA vasculitis as determined by relapse-free remission at 18, 24 and 36 months from enrollment. The investigators are looking to enroll and randomize 200 subjects with ANCA vasculitis on rituximab-induced continuous B cell depletion for a minimum of two years to one of two arms as follows:

Intermittent B cell depletion with rituximab re-dosing upon B cell return: Subjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose (spaced 2-3 weeks apart) once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing.
Hold continuous dosing with rituximab with re-dosing upon a significant ANCA titer increase: For MPO, a significant increase will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects will not receive regularly scheduled every six-month doses of rituximab and will instead be seen in clinic to have their ANCA titer monitored every three months. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, ~2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start.

Conditions: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Being tested: Rituximab
Keywords: rituximab, maintenance, remission
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.

RituximabDrug
Also called Rituxan
re-dosing dependent on interventional arm parameter.

Study groups in NCT02749292
Study group	Role	What they receive
B cell reconstitution	Active comparator	Subjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing. Receives: Drug: Rituximab
Serologic ANCA flare	Active comparator	Subjects will not receive regularly scheduled every six-month doses of rituximab (1000mg IV) and will instead be seen in clinic for ANCA titer monitoring every 3 months. Re-dosing will occur upon a significant ANCA titer increase. For MPO, a significant rise will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, spaced ~2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start. Receives: Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2
Relapses recording period was from 6/1/2016 to 12/31/2021. The outcome was reported as the number of participants with disease relapse who had either positive ANCA titers specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64.
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)

Secondary outcomes (9)

Number of Patients Affected by Serious Adverse Events
Number of patients with serious adverse events (SAEs), including all episodes of late onset neutropenia (LON). SAE are defined in the Serious adverse event section. Serious adverse events were reported over the entire study period (5.5 years)
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events
Number of disease relapse added with the number of SAE in each group
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Number of Patients With Hypogammaglobulinemia
Hypogammaglobulinemia defined as an IgG < 250mg/dL
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Patient Survival
number of deaths throughout the study.
Measured: 5.5 years
Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores
The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status and is commonly used in health economics as a variable in the quality-adjusted life year calculation to determine the cost-effectiveness of a health treatment. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: Assessed throughout the study period, every 6 months unless such time point was not reached or was missed by the patient. Median follow-up period is of 4.1 years (IQR, 2.5 - 5.0)
Mean Number of Rituximab Infusions Per Subject
The rituximab utilization was measured in how many times a subject received Rituximab throughout the study which was then averaged for all subjects in each treatment arm, including those who did not receive any infusion.
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Organ Damage as Assessed by the Vasculitis Damage Index (VDI).
The Vasculitis Damage Index (VDI) is a validated formal assessment tool in ANCA-associated vasculitis clinical trials. The VDI distinguishes vasculitis-induced chronic damage from active inflammation or persistent disease. Each item represents a disease manifestation and is given a score (of 1) if present for at least 3 months. Neither the cause of damage (vasculitis vs treatment) nor an ongoing activity are taken into consideration. The VDI includes 64 items categorized into 11 groups (by organ system) and the scored items are summed to give a total score ranging from 0 to 64. A higher score means more accrued damage.
Measured: 3 years starting at inclusion
Number of Major Relapses Defined as a BVAS/WG ≥ 3
The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64.
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Number of Infections
Number of infections mild and severe, whether they were treated or not with antibiotics
Measured: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201631 Jan 2022

First posted22 Apr 2016 (estimated)
Study startJun 2016
Primary completion31 Jan 2022
Study completion31 Jan 2022

Why it stopped: Due to the coronavirus disease 2019 (COVID-19) pandemic and the deleterious impact of rituximab on vaccination efficacy, the trial was concluded before reaching the target enrollment of 200.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)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 Massachusetts General HospitalThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 115 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02749292
Sponsor's protocol ID: 2015P002541
Acronym: MAINTANCAVAS
Status last verified: Jul 2023
First submitted: 1 Mar 2016
Last updated: 27 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011 May;20(3):263-70. doi: 10.1097/MNH.0b013e3283456731.
PubMed 21422922
Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169.
PubMed 20647198
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.
PubMed 20647199
Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003 Jul 3;349(1):36-44. doi: 10.1056/NEJMoa020286.
PubMed 12840090
Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277.
PubMed 23902481
Pendergraft WF 3rd, Cortazar FB, Wenger J, Murphy AP, Rhee EP, Laliberte KA, Niles JL. Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis. Clin J Am Soc Nephrol. 2014 Apr;9(4):736-44. doi: 10.2215/CJN.07340713. Epub 2014 Mar 13.
PubMed 24626432
Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Puechal X, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231.
PubMed 25372085
Han WK, Choi HK, Roth RM, McCluskey RT, Niles JL. Serial ANCA titers: useful tool for prevention of relapses in ANCA-associated vasculitis. Kidney Int. 2003 Mar;63(3):1079-85. doi: 10.1046/j.1523-1755.2003.00821.x.
PubMed 12631091
Alberici F, Smith RM, Jones RB, Roberts DM, Willcocks LC, Chaudhry A, Smith KG, Jayne DR. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford). 2015 Jul;54(7):1153-60. doi: 10.1093/rheumatology/keu452. Epub 2014 Dec 3.
PubMed 25477054
Zonozi R, Cortazar FB, Jeyabalan A, Sauvage G, Nithagon P, Huizenga NR, Rosenthal JM, Sipilief A, Cosgrove K, Laliberte KA, Rhee EP, Pendergraft WF 3rd, Niles JL. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis. 2024 Feb 15;83(3):351-359. doi: 10.1136/ard-2023-224489.
PubMed 38123922

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing Based on B-cell Reconstitution vs a Serologic ANCA Flare
ClinicalTrials.gov ID: NCT02749292
Acronym / sponsor ID: MAINTANCAVAS / 2015P002541
Conditions: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Keywords: rituximab, maintenance, remission
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to the coronavirus disease 2019 (COVID-19) pandemic and the deleterious impact of rituximab on vaccination efficacy, the trial was concluded before reaching the target enrollment of 200.
Enrolment: 115 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: Jun 2016
Primary completion: 31 Jan 2022 (actual)
Study completion: 31 Jan 2022 (actual)
First posted: 22 Apr 2016 (estimated)
Results: Posted 27 Jul 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

A rise in ANCA titers and reconstitution of B cells are promising biomarkers of impending disease relapse following treatment with rituximab4-6

Intermittent B cell depletion with rituximab re-dosing upon B cell return: Subjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose (spaced 2-3 weeks apart) once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing.
Hold continuous dosing with rituximab with re-dosing upon a significant ANCA titer increase: For MPO, a significant increase will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects will not receive regularly scheduled every six-month doses of rituximab and will instead be seen in clinic to have their ANCA titer monitored every three months. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, ~2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
B cell reconstitution	Active comparator	Drug: RituximabSubjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing.
Serologic ANCA flare	Active comparator	Drug: RituximabSubjects will not receive regularly scheduled every six-month doses of rituximab (1000mg IV) and will instead be seen in clinic for ANCA titer monitoring every 3 months. Re-dosing will occur upon a significant ANCA titer increase. For MPO, a significant rise will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, spaced ~2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start.

Who may qualify

Ages: 18 to 82 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

All patients must be able and willing to give written informed consent and comply with the requirements of the study protocol.
Diagnosis: ANCA vasculitis as defined by a positive MPO- and/or PR3-ANCA test together with clinical features characteristic of ANCA-positive diseases as detailed in the 2012 Chapel Hill Consensus Conference Definitions(18).
eGFR ≥ 73 cc/min/1.73m2
Age: 18-82 years old
Treated with rituximab-induced continuous B cell depletion at regularly scheduled interval with a goal of undetectable B cells for at least 24 months

Key exclusion criteria (7 listed)

Secondary Disease: disease suspected to be induced by levamisole-adulterated cocaine
All transplanted patients
Treatment: additional immunosuppressive agents other than rituximab and/or total daily prednisone dose ≥ 7.5 milligrams
Hypogammaglobulinemia: IgG level < 300 mg/dL
Terminal cancer or other primary illness with life expectancy of less than 36 months

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
RituximabAlso: Rituxanre-dosing dependent on interventional arm parameter.	Drug	B cell reconstitution, Serologic ANCA flare

Primary outcome

Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Relapses recording period was from 6/1/2016 to 12/31/2021. The outcome was reported as the number of participants with disease relapse who had either positive ANCA titers specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). The Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG ) is a form with 34 predefined items grouped into 9 organ systems. The items are clinical features observed in patients with active ANCA vasculitis. Each item has a specified weight of either 3 or 1, depending on whether it reflects major or minor disease activity. The total BVAS/WG score is the weighted sum of individual manifestations that are present and believed to be due to active ANCA vasculitis. Higher scores reflect more active disease. BVAS/WG scores range from 0 to 64.

9 secondary outcomes

Number of Patients Affected by Serious Adverse Events
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Composite of Disease Relapse (Defined a BVAS/WG ≥ 2) and Serious Adverse Events
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Number of Patients With Hypogammaglobulinemia
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Patient Survival
Time frame: 5.5 years
Health-related Quality of Life as Assessed by the Short Form Health Survey (SF-36) Scores
Time frame: Assessed throughout the study period, every 6 months unless such time point was not reached or was missed by the patient. Median follow-up period is of 4.1 years (IQR, 2.5 - 5.0)
Mean Number of Rituximab Infusions Per Subject
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Organ Damage as Assessed by the Vasculitis Damage Index (VDI).
Time frame: 3 years starting at inclusion
Number of Major Relapses Defined as a BVAS/WG ≥ 3
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)
Number of Infections
Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)

Results and safety

Results posted to the registry on 27 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
B Cell Reconstitution	58	36
Serologic ANCA Flare	57	31

Primary outcome: Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2

Time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0). Count of participants. Unit: Participants

Measure	B Cell Reconstitution n = 58	Serologic ANCA Flare n = 57
PR3	1	7
MPO	4	7

B Cell Reconstitution vs Serologic ANCA Flare: Hazard Ratio (HR): 0.37 (95% CI 0.15 to 0.90), p = 0.045, Log Rank

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: June 1 2016 to December 2021 (5 years and 6 months). The earliest Adverse event reported was on 2/6/2017 and the latest adverse event reported was on 12/25/2021. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
B Cell Reconstitution	15 of 58 (25.9%)	46 of 58 (79.3%)	2 of 58
Serologic ANCA Flare	14 of 57 (24.6%)	44 of 57 (77.2%)	0 of 57

Limitations and caveats (from the sponsor): The trial has several limitations: 1. It was open-label. 2. it only enrolled patients on continuous B cell depletion for a minimum of 2 years 3. it took place in a single center.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21422922Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011 May;20(3):263-70. doi: 10.1097/MNH.0b013e3283456731.
Background: PubMed 20647198Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169.
Background: PubMed 20647199Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905.
Background: PubMed 12840090Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003 Jul 3;349(1):36-44. doi: 10.1056/NEJMoa020286.
Background: PubMed 23902481Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277.
Background: PubMed 24626432Pendergraft WF 3rd, Cortazar FB, Wenger J, Murphy AP, Rhee EP, Laliberte KA, Niles JL. Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis. Clin J Am Soc Nephrol. 2014 Apr;9(4):736-44. doi: 10.2215/CJN.07340713. Epub 2014 Mar 13.
Background: PubMed 25372085Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, Maurier F, Decaux O, Ninet J, Gobert P, Quemeneur T, Blanchard-Delaunay C, Godmer P, Puechal X, Carron PL, Hatron PY, Limal N, Hamidou M, Ducret M, Daugas E, Papo T, Bonnotte B, Mahr A, Ravaud P, Mouthon L; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231.
Background: PubMed 12631091Han WK, Choi HK, Roth RM, McCluskey RT, Niles JL. Serial ANCA titers: useful tool for prevention of relapses in ANCA-associated vasculitis. Kidney Int. 2003 Mar;63(3):1079-85. doi: 10.1046/j.1523-1755.2003.00821.x.
Background: PubMed 25477054Alberici F, Smith RM, Jones RB, Roberts DM, Willcocks LC, Chaudhry A, Smith KG, Jayne DR. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford). 2015 Jul;54(7):1153-60. doi: 10.1093/rheumatology/keu452. Epub 2014 Dec 3.
Derived from this study: PubMed 38123922Zonozi R, Cortazar FB, Jeyabalan A, Sauvage G, Nithagon P, Huizenga NR, Rosenthal JM, Sipilief A, Cosgrove K, Laliberte KA, Rhee EP, Pendergraft WF 3rd, Niles JL. Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial. Ann Rheum Dis. 2024 Feb 15;83(3):351-359. doi: 10.1136/ard-2023-224489.
Individual participant dataSharing planned: No

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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.

John L Niles, MD principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Rituximab in people with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, run by Massachusetts General Hospital 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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 27 Jul 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Patients With Disease Relapse(s) as Defined by a Birmingham Vasculitis Activity Score for Wegner's Granulomatosis (BVAS/WG) ≥ 2 (time frame: Median follow-up period of 4.1 years (IQR, 2.5 - 5.0)). 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 NCT02749292, which also lists 10 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 27 Jul 2023.