Low-dose Glucocorticoid Vasculitis Induction Study

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Wegener’s Granulomatosis
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Brief Title

Low-dose Glucocorticoid Vasculitis Induction Study

Official Title

Low-dose Glucocorticoids Plus Rituximab Versus High-dose Glucocorticoids Plus Rituximab for Remission Induction in ANCA-associated Vasculitis; a Multicentre, Open Label, Randomised Control Trial

Brief Summary

      Previous reports suggested conventional immunosuppressants such as cyclophosphamide could not
      reduce glucocorticoid dose in remission induction in ANCA-associated vasculitis because of
      lower remission rate and higher relapse rate. However those reports didn't include rituximab.

      B cell depletion therapy by rituximab is a new strategy for remission induction in
      ANCA-associated vasculitis. The RAVE and RITUXVAS trial (NEJM 2010, both) showed high-dose
      glucocorticoid plus rituximab had roughly the same efficacy and safety as high-dose
      glucocorticoid plus IV-cyclophosphamide. In addition, recent retrospective observational
      studies reported low-dose glucocorticoid plus rituximab led to re-induction in severe
      relapsing ANCA-associated vasculitis.

      Thus, the investigators aim to investigate whether rituximab can reduce glucocorticoid dose
      in induction remission in ANCA-associated vasculitis (to show non-inferiority for efficacy
      between low-dose and high-dose glucocorticoid plus rituximab). Participants will be
      randomised to the "low-dose glucocorticoid plus rituximab" or the high-dose glucocorticoid
      plus rituximab" groups. Primary endpoint is proportion of remission at 6 months, then data
      regarding relapse and long-term safety will be collected until 24 months.

      The study has been designed by the principal and coordinating investigators. It will include
      140 participants from 18 hospitals in Japan. It is funded by Chiba University Hospital and
      Chiba East Hospital.

Detailed Description

      ANCA (anti-neutrophil cytoplasmic antibody)-associated vasculitis is characterised by small
      vessel vasculitis and presence of autoantibodies, ANCA. It can be a life-threatening disease
      with renal/respiratory failure. Current standard therapy in induction remission for
      ANCA-associated vasculitis is combination of high-dose glucocorticoid and
      IV-cyclophosphamide. This regimen is effective (remission rate; 80-90%), but often cause
      various glucocorticoid-related side effects. Especially, infection is related to death. Thus
      a new regimen reducing glucocorticoid dose is required.

Study Phase

Phase 4

Study Type

Interventional

Primary Outcome

Proportion of the patients achieving remission

Secondary Outcome

 Time to remission

Condition

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Intervention

Rituximab

Study Arms / Comparison Groups

 Low-dose glucocorticoid
Description:  Prednisolone will be commenced with dose of 0.5mg/kg/day and will be tapered and off within 6 months. If a patient fails to achieve BVAS=0, an investigator can postpone the procedure of stopping prednisolone (prednisolone 5mg/day x 2 weeks, 4mg/day x 2 weeks, 3mg/day x 4 weeks, 2mg/day x 4 weeks, 1mg/day x 4 weeks, then off prednisolone). Once starting the procedure, prednisolone must be off after 16 weeks. Patients will also receive rituximab (375mg/m2/w x4).
After achieving remission, patients will be receive rituximab (1g/body or 0.5g/bodyx2) every 6 months as remission maintenance therapy.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

140

Start Date

October 2014

Completion Date

June 2021

Primary Completion Date

December 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Provision of written informed consent by a patient or a surrogate decision maker

          2. Age=>20 years

          3. New clinical diagnosis of ANCA-associated vasculitis (granulomatosis with
             polyangiitis, microscopic polyangiitis or renal limited ANCA-associated vasculitis)
             consistent with the 2012 Chapel Hill consensus definitions

          4. Positive test by ELISA for proteinase 3-ANCA or myeloperoxidase-ANCA

        Exclusion Criteria:

          1. Prior treatment for ANCA-associated vasculitis before trial entry

          2. ANCA-associated vasculitis related glomerulonephritis (eGFR<15ml/min) or alveolar
             hemorrhage (oxygen inhalation >2L/min)

          3. Presence of another multisystem autoimmune disease

          4. Known infection with HIV; a past or current history of hepatitis B virus or hepatitis
             C virus infection

          5. Desire to bear children, pregnancy or lactating

          6. History of malignancy within the past 5 years or any evidence of persistent malignancy

          7. Ongoing or recent (last 1 year) evidence of active tuberculosis

          8. Severe allergy or anaphylaxis to monoclonal antibody therapy

          9. Any concomitant condition anticipated to likely require oral systemic glucocorticoids,
             immunosuppressants, biologics, plasma exchange or IVIg

         10. Any biological B cell depleting agent (such as rituximab or belimumab) within the past
             6 months

         11. Other conditions, in the investigator's opinion, inappropriate for the trial entry

Gender

All

Ages

20 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Hiroshi Nakajima, M.D., Ph.D, ,

Location Countries

Japan

Location Countries

Japan

Administrative Informations

NCT ID

NCT02198248

Organization ID

G25051

Secondary IDs

UMIN000014222

Responsible Party

Principal Investigator

Study Sponsor

Chiba University

Study Sponsor

Hiroshi Nakajima, M.D., Ph.D, Principal Investigator, Chiba University Hospital

Verification Date

January 2021