Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00748644
Other study ID # P 070703
Secondary ID
Status Completed
Phase Phase 3
First received September 5, 2008
Last updated March 1, 2018
Start date October 2008
Est. completion date June 2013

Study information

Verified date January 2012
Source Assistance Publique - Hôpitaux de Paris
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Study of the efficacy of rituximab for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of rituximab versus azathioprine


Description:

Randomized, controlled, national, multicenter, prospective study to compare between azathioprine (conventional therapy) and rituximab in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant, mainly intravenous pulses of cyclophosphamide, and plasma exchanges and/or polyvalent immunoglobulins when indicated) after the first flare of the disease (new diagnosis) or after a relapse. It is planned to stratify patients by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients who have already received biologics (antiCD20, antiTNFα) will not be included. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by azathioprine for 18 months or a rituximab infusion every 6 months until month 18 (i.e. a total of 4 infusions), at the dose of 375 mg/m2 (maximum dosage, 500 mg). ANCA status and CD19+ lymphocyte count will be monitored but will not be used to adjust therapy. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with Wegener's granulomatosis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).


Recruitment information / eligibility

Status Completed
Enrollment 117
Est. completion date June 2013
Est. primary completion date March 2013
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria:

- Wegener's granulomatosis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission.

- Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent according to current French guideline, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins).

- Interval of 1 month between the end of the immunosuppressant treatment and the randomization time

- Age > 18 years and < 75 years when the diagnosis is confirmed.

- Informed and having signed the consent form to take part in the study.

Exclusion Criteria:

- Other systemic vasculitis

- Secondary vasculitis (following neoplastic disease or an infection in particular)·

- Induction treatment with a regimen not corresponding to that recommended in France.

- Patient who has not achieved remission.·

- Patient who has already received a treatment by biological agents (monoclonal antibody - antiCD20 or antiTNFa).

- Incapacity or refusal to understand or sign the informed consent form.

- Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study. Non-compliance·

- Allergy, documented hypersensitivity or contraindication to the study medication (cyclophosphamide, corticosteroids, azathioprine, rituximab),

- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.

- Patients receiving allopurinol cannot be included if the allopurinol must absolutely be maintained.

- Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of contraception throughout the duration of immunosuppressive treatment up to 1 year after the last infusion of rituximab

- Infection by HIV, HCV or HBV

- Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV infection, etc.).

- Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8, HCV, HIV, tuberculosis).

- Progressive cancer or malignant blood disease diagnosed during the 5 years before the diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or those cured of a cancer or a malignant blood disorder for more than 5 years and not taking any antineoplastic agents for more than 5 years may be included.

- patients presenting a systemic disease receiving protocolized treatments (azathioprine, rituximab) which could have unexpected and inappropriate side effects.

- Participation in another clinical research protocol during the 4 weeks before inclusion.

- Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.

- No social security

- Churg and Strauss syndrome

- viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks before the inclusion

- history of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the first year before the inclusion

- History of chronic and severe or recurrent infection or history of preexisting disease predisposing to severe infection

- Severe immunodepression

- Administration of live vaccine in the four weeks before inclusion

- severe chronic obstructive pulmonary diseases (VEMS < 50 % or dyspnea grade III)

- chronic heart failure stade III and IV (NYHA)

- History of recent acute coronary syndrome

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Rituximab
rituximab infusion will be performed at J1, J15, M6, M12 and M18(i.e. a total of 5 infusions), at the dose of 500 mg at a fixed dosage. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.
Azathioprine
azathioprine (2 mg/kg/d) for 12 months, then progressively tapered until its discontinuation at month 22. All patients received corticosteroids, starting from induction with prednisone (or equivalent) at a dose of 1 mg/kg/day with gradual tapering according to a regimen adjusted to body weight over a mean of 18 months since diagnosis.

Locations

Country Name City State
France Hopital Cochin Paris

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of major relapse (BVAS>10) in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up) 28 months
Secondary To assess the number of adverse events and their severity in each group 28 months
Secondary Number of patients with ANCA in each group 28 months
Secondary mortality rate in each group 28 months
Secondary number of minor relapse in each group 28 months
Secondary Cumulated dose and the length of corticosteroid treatment in each group at 28 months 28 months
Secondary same criteria with an analysis at 6 months after the end of maintenance treatment 24 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT01729624 - PRO Development for ANCA Associated Vasculitis N/A
Terminated NCT02474888 - Pharmacokinetic Study of Rituximab Induction Regimen in ANCA-associated Vasculitis
Active, not recruiting NCT02198248 - Low-dose Glucocorticoid Vasculitis Induction Study Phase 4
Completed NCT02190916 - Vasculitis Illness Perception (VIP) Study N/A
Recruiting NCT01241305 - One-Time DNA Study for Vasculitis
Recruiting NCT02967068 - VCRC Tissue Repository
Completed NCT01731561 - Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis Phase 3
Not yet recruiting NCT06350110 - Fourth-gen CAR T Cells Targeting BCMA/CD19 for Refractory Systemic Lupus Erythematosus (SLE) Phase 1/Phase 2
Completed NCT02190942 - VCRC Patient Contact Registry Patient-Reported Data Validation Study
Not yet recruiting NCT02126098 - Observation Study of Clinical Manifestation and Outcome in Chinese Patients With Pulmonary Vasculitis N/A
Terminated NCT01586858 - Rituximab for ANCA-associated Vasculitis (RAVE) Long-Term Follow-Up Study N/A
Completed NCT00307593 - RATTRAP: Infliximab Versus Rituximab in Systemic Necrotizing Vasculitides N/A
Completed NCT02190929 - Educational Needs of Patients With Systemic Vasculitis N/A
Terminated NCT01408836 - Plasma Exchange for Renal Vasculitis Phase 2/Phase 3
Terminated NCT05376319 - PR3-AAV Resilient Remission or PRRR Phase 2
Completed NCT02476292 - Impact of Vasculitis on Employment and Income N/A
Completed NCT02169219 - Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis Phase 4
Completed NCT01613599 - An Observational Study of The Safety of MabThera/Rituxan (Rituximab) in Participants With Granulomatosis With Polyangiitis (Wegener's) or Microscopic Polyangiitis
Active, not recruiting NCT05716334 - Biosimilars of Rituximab in ANCA-associated Vasculitis Compared to the Originator
Completed NCT00307671 - Treatment of Necrotizing Vasculitides for Patients Older Than 65 Years Phase 4