Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

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Brief Title

Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Official Title

A Prospective, Multicentric, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Remission MAINtenance Using Extended Administration of Prednisone in Systemic Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis.

Brief Summary

      Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood
      of disease control and temporary remission. However, most patients have recurrent relapses
      that lead to damage and require repeated treatment associated with long-term morbidity and
      death.

      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile .
      Although rituximab is becoming the standard of care for maintenance therapy in these
      patients, relapse still occurs and the optimal duration of prednisone therapy remains
      debated.

      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side
      effects. On the other hand, most European trials propose late withdrawal (>18 months) given a
      lower observed relapse rate on long-term low dose glucocorticoids treatment.

      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant
      variable explaining the variability between the proportions of ANCA-associated vasculitis
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect
      because of the absence of dedicated randomized trial. This meta-analysis concluded that
      combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12
      months).

      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and
      two thirds of the nonsevere relapses occurred when patients were off prednisone.

      The trial detailed here is the first prospective trial evaluating the length of
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
    

Detailed Description

      Immunosuppressive therapy of granulomatosis with polyangiitis (GPA, Wegener's) and
      microscopic polyangiitis (MPA) has transformed the outcome from death to a strong likelihood
      of disease control and temporary remission. However, most patients have recurrent relapses
      that lead to damage and require repeated treatment associated with long-term morbidity and
      death.

      Rituximab has been shown to be as effective as cyclophosphamide to induce remission and
      maintenance of remission in severe GPA and MPA patients, with an acceptable safety profile.
      Although rituximab is becoming the standard of care for maintenance therapy in these
      patients, relapse still occurs and the optimal duration of prednisone therapy remains
      debated.

      On the one hand, most US studies use early withdrawal (6-12 months) because of feared side
      effects. On the other hand, most European trials propose late withdrawal (>18 months) given a
      lower observed relapse rate on long-term low dose glucocorticoids treatment.

      In a systematic review and meta-analysis, glucocorticoids regimen was the most significant
      variable explaining the variability between the proportions of ANCA-associated vasculitis
      patients with relapses. Nevertheless, it was an indirect estimation of treatment effect
      because of the absence of dedicated randomized trial. This meta-analysis concluded that
      combined longer-term (i.e. >12 months) use of low dose prednisone or nonzero glucocorticoids
      target is associated with a 20% reduction of relapse compared to early withdrawal (i.e. ≤12
      months).

      The relapse rate in patients with early glucocorticoids (10-12 months) withdrawal was
      provided in two studies and was of 37 and 34%, respectively. By contrast, the relapse rate in
      patients with late prednisone withdrawal (18-24 months) and receiving rituximab as
      maintenance treatment was 14% at 24 months in the MAINRITSAN trial. Of note, the decision to
      withdraw glucocorticoids after 18 months was left to physician's discretion in this study and
      two thirds of the nonsevere relapses occurred when patients were off prednisone.

      The trial detailed here is the first prospective trial evaluating the length of
      glucocorticoid administration as remission adjunctive treatment for patients with GPA or MPA.
    


Study Type

Interventional


Primary Outcome

Relapse-free survival, relapse being defined as BVAS > 0.

Secondary Outcome

 Compare the rate of serious adverse events between Inclusion and Month 30 after randomization

Condition

Granulomatosis With Polyangitis

Intervention

Prednisone 5mg/day extended of 12 additional months

Study Arms / Comparison Groups

 Prednisone 5mg/day extended of 12 additional months
Description:  Prednisone 5mg/day will be administered from Day 1 to Month 12

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

146

Start Date

August 20, 2019

Completion Date

June 4, 2024

Primary Completion Date

June 4, 2024

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a diagnosis of MPA or GPA independently of ANCA status,

          -  Patient aged of 18 years or older,

          -  Patients with newly-diagnosed disease or relapsing disease at the time of screening,
             with an inactive disease defined as a BVAS = 0,

          -  Patients receiving maintenance infusion of rituximab 500 mg at 6 and 12 months after
             the start of vasculitis induction

          -  Patients receiving 5-10 mg/day of prednisone at screening,

          -  Patient able to give written informed consent prior to participation in the study.

          -  At Inclusion visit day, patient must be between 5 and 10 mg/day prednisone and at
             randomization visit day (D1), patient must be at 5 mg/day prednisone

        Exclusion Criteria:

          -  Patients with EGPA, or other vasculitides, defined by the ACR criteria and/or the
             Chapel Hill Consensus Conference,

          -  Patients with vasculitis with active disease defined as a BVAS >0,

          -  Patients with acute infections or chronic active infections (including HIV, HBV or
             HCV),

          -  Patients with active cancer or recent cancer (<5 years), except basocellular carcinoma
             and prostatic cancer of low activity controlled by hormonal treatment,

          -  Pregnant women and lactation. Patients with childbearing potential should have
             reliable contraception for the all duration of the study,

          -  Patients with other uncontrolled diseases, including drug or alcohol abuse, severe
             psychiatric diseases, that could interfere with participation in the trial according
             to the protocol,

          -  Patients included in other investigational therapeutic study within the previous 3
             months,

          -  Patients suspected not to be observant to the proposed treatments,

          -  Patients who have white blood cell count ≤4,000/mm3,

          -  Patients who have platelet count ≤100,000/mm3,

          -  Patients who have ALT or AST level greater than 3 times the upper limit of normal that
             cannot be attributed to underlying MPA-GPA disease,

          -  Patients unable to give written informed consent prior to participation in the study.

          -  Patients with contraindication to use rituximab,
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jean-Christophe LEGA, Pr, 04.78.86.19.79, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT03290456

Organization ID

69HCL17_0020


Responsible Party

Sponsor

Study Sponsor

Hospices Civils de Lyon


Study Sponsor

Jean-Christophe LEGA, Pr, Principal Investigator, Hospices Civils de Lyon


Verification Date

November 2019