Trial record 2 of 2 for:    mainritsan

Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis (MAINRITSAN 2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01731561
First received: October 12, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.


Condition Intervention Phase
Granulomatosis With Polyangiitis
Microscopic Polyangiitis
Renal Limited Forms
Drug: Rituximab (Arm B)
Drug: Rituximab (Arm A)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Number of relapses [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 16 months follow-up)


Secondary Outcome Measures:
  • Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies) [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    Number of patients with ANCA in each group

  • Number of adverse events [ Time Frame: at 28 months ] [ Designated as safety issue: Yes ]
    To assess the number of adverse events and their severity in each group

  • Mortality rate [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    To assess mortality rate in each group

  • Number of minor relapse [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    number of minor relapse in each group

  • Cumulated dose of corticosteroid treatment [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    Cumulated dose of corticosteroid treatment in each group at 34 months

  • Number and severity of damages [ Time Frame: at 28 months ] [ Designated as safety issue: Yes ]
    Number and severity of damages in each group

  • Evolution of ANCA and the link of the clinical events [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    Evolution of ANCA in each group and the link of the clinical events

  • Distribution of events by severity [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).

  • Length of corticosteroid treatment [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    The length of corticosteroid treatment in each group at 34 months

  • Rate of B-Lymphocytes CD-19 and the link of the clinical events [ Time Frame: at 28 months ] [ Designated as safety issue: No ]
    The rate of B-Lymphocytes CD-19 and the link of the clinical events


Estimated Enrollment: 166
Study Start Date: November 2012
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab infusion according biological parameters
Rituximab infusion based on ANCA and CD19 lymphocytes
Drug: Rituximab (Arm B)
Rituximab infusion will be performed at D1 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. 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.
Active Comparator: Systematic rituximab infusion
Semestrial rituximab infusion until 18 months
Drug: Rituximab (Arm A)
Rituximab infusion will be performed at D1, D15, 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.

Detailed Description:

Randomized, controlled, national, multicenter, prospective study to compare systematic rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant after the first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified 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 will be included at the time of remission and then randomized. They will receive maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 16 month period. Patients with granulomatosis with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Granulomatosis with Polyangiitis 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, 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, or rituximab).
  • Interval of 1 month between the end of the immunosuppressant treatment and the randomization time if cyclophosphamide or methotrexate were used, interval between 4 and 6 months if rituximab was used
  • Age > 18 years without age limit higher 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.
  • 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.
  • 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.
  • 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, unrelated to vasculitis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01731561

Locations
France
Cochin Hospital
Paris, France, 75014
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Chair: Loic Guillevin, MD, PhD Cochin Hospital, Paris, France
Study Chair: Pierre Charles, MD Institut mutualiste, Paris, France
  More Information

Additional Information:
No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01731561     History of Changes
Other Study ID Numbers: P110146, 2012-001963-66
Study First Received: October 12, 2012
Last Updated: April 11, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Granulomatosis with Polyangiitis
Microscopic polyangiitis
Renal limited forms
ANCA-associated vasculitis
Rituximab

Additional relevant MeSH terms:
Vasculitis
Wegener Granulomatosis
Systemic Vasculitis
Microscopic Polyangiitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 23, 2014