ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 10 of 36 for:    "Churg Strauss syndrome"

Rituximab in Eosinophilic Granulomatosis With Polyangiitis (REOVAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02807103
Recruitment Status : Recruiting
First Posted : June 21, 2016
Last Update Posted : March 19, 2018
Sponsor:
Collaborator:
French Vasculitis Study Group (FVSG)
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Phase III, comparative, multicenter, randomized, controlled, double-blind and superiority research, comparing rituximab-based regimen with conventional therapeutic strategy for the induction of remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA).

Patients with newly diagnosed or relapsing EGPA will be randomized in a 1:1 ratio to receive:

  • Experimental therapeutic strategy based on the use of rituximab (experimental group)
  • Conventional therapeutic strategy based on Five-Factor Score (FFS)-assessed disease severity (comparative group)

Condition or disease Intervention/treatment Phase
Eosinophilic Granulomatosis With Polyangiitis (EGPA) Drug: Rituximab Drug: Placebo-rituximab Drug: Cyclophosphamide Drug: Placebo-cyclophosphamide Phase 3

Detailed Description:

Systemic vasculitides are inflammatory diseases of blood vessels, among which anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are often severe with life-threatening manifestations or complications. AAV include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome).

Cytotoxic drugs and glucocorticoids have been the standard of care for remission induction for nearly five decades. This regimen improved the outcome of severe AAV from death to a strong likelihood of disease control and temporary remission. However, a remission is not obtained in all patients with this combination of drugs, and most patients experience disease flares requiring repeated treatment with associated significant morbidity and mortality.

In 2 prospective controlled trials, rituximab, an anti-CD20 monoclonal antibody, was shown to be non inferior to cyclophosphamide to induce remission with an acceptable safety profile in patients with systemic GPA and MPA. However, patients with EGPA were not included in these trials and rituximab has not been evaluated prospectively to induce remission in this disease which pathogenesis is complex and not only restricted to ANCA responsibility.

In patients with EGPA, overall survival is good when treatment is stratified according to prognostic factors (Five Factor Score) but long-term outcome is not so good since relapses occur in more than 40% of patients, leading to high cumulative morbidity and damage. In small retrospective studies, rituximab seems promising as a remission-induction agent in patients with EGPA, independently from the ANCA status.

The trial detailed here is the first prospective trial evaluating rituximab as induction-remission treatment for EGPA.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of Rituximab-based Regimen Compared to Conventional Therapeutic Strategy For Remission Induction In Patients With Newly-Diagnosed or Relapsing Eosinophilic Granulomatosis With Polyangiitis. Prospective, Randomized, Controlled, Double-blind Study
Actual Study Start Date : December 5, 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Rituximab with FFS=0

All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group.

Patients with FFS=0 will receive 1 gram of rituximab at day 1 and day 15 as induction treatment

Drug: Rituximab
1 g intravenous pulse at day1 and day15
Other Name: Mabthera

Placebo Comparator: Conventional therapy with FFS=0

All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group.

Patients with FFS=0 will receive placebo-rituximab at day 1 and day 15.

Drug: Placebo-rituximab
intravenous pulses at day1 and day15
Other Name: nacl

Experimental: Rituximab with FFS≥1

All patients in the rituximab group will receive corticosteroids with a predefined tapering schedule similar to the conventional therapy group.

Patients with FFS≥1 will receive a total of 9 pulses :

  • 1 gram of rituximab at day 1 and day 15 as induction treatment
  • placebo-cyclophosphamide at days 1, 15, 29, 50, 71, 92, 113, 134 and 155.

Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.

Drug: Rituximab
1 g intravenous pulse at day1 and day15
Other Name: Mabthera

Drug: Placebo-cyclophosphamide
intravenous 7 pulses : at days 29, 50, 71, 92, 113, 134 and 155.
Other Name: Nacl

Active Comparator: Conventional therapy with FFS≥1

All patients will receive corticosteroids with a predefined tapering schedule similar to the experimental group.

Patients with FFS≥1 will receive intravenous pulses of cyclophosphamide for a total of 9 pulses: 600 mg/m2 at days 1, 15 and 29, and then 500 mg-fixed dose at days 50, 71, 92, 113, 134 and 155.

Maintenance therapy by azathioprine will be started at day 180 according to the standard of care of these patients, as recommended by the French Vasculitis Study Group.

Drug: Cyclophosphamide
intravenous 9 pulses : 600 mg/m2 at days 1, 15 and 29, and then 500 mg-fixed dose at days 50, 71, 92, 113, 134 and 155.
Other Name: endoxan




Primary Outcome Measures :
  1. Number of patients in complete remission (defined by a Birmingham Vasculitis Activity Score (BVAS) of 0 and a prednisone dose ≤7.5 mg/day ) [ Time Frame: 180 days ]

Secondary Outcome Measures :
  1. Number of adverse events [ Time Frame: 180 days ]
    expressed as adverse events according to the CTCAE toxicity grading system per patient-year for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions

  2. Number of adverse events [ Time Frame: 360 days ]
    expressed as adverse events according to the CTCAE toxicity grading system per patient-year for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hemorrhagic cystitis, malignancies, venous thromboembolic events, hospitalization resulting either from the disease or from a complication due to the study treatment, infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions

  3. Area under the curve for corticosteroids [ Time Frame: 180 days ]
    To measure the corticosteroid dose and to compare the corticosteroid sparing effect of rituximab versus conventional therapy

  4. Area under the curve for corticosteroids [ Time Frame: 360 days ]
    To measure the corticosteroid dose and to compare the corticosteroid sparing effect of rituximab versus conventional therapy

  5. Number of sequelae assessed by the Vasculitis Damage Index [ Time Frame: 180 days ]
  6. Number of sequelae assessed by the Vasculitis Damage Index [ Time Frame: 360 days ]
  7. ANCA titers and CD19+cells [ Time Frame: 180 days ]
  8. ANCA titers and CD19+cells [ Time Frame: 360 days ]
  9. Health Assessment Questionnaire (HAQ) score [ Time Frame: 180 days ]
    to evaluate functional disability

  10. Health Assessment Questionnaire (HAQ) score [ Time Frame: 360 days ]
    to evaluate functional disability

  11. Short Form-36 score [ Time Frame: 180 days ]
    to evaluate quality of life

  12. Short Form-36 score [ Time Frame: 360 days ]
    to evaluate quality of life



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a diagnosis of EGPA 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 active disease defined as a Birmingham Vasculitis Activity Score (BVAS) ≥3,
  • Patients within the first 21 days following initiation/increase of corticosteroids at a dose ≤ 1 mg/kg/day (pulses of methylprednisolone before oral corticosteroid therapy are authorized) ,
  • Patient able to give written informed consent prior to participation in the study.

Exclusion Criteria:

  • Patients with GPA, MPA, or other vasculitides, defined by the ACR criteria and/or the Chapel Hill Consensus Conference,
  • Patients with vasculitis in remission of the disease defined as a BVAS <3,
  • Patients with severe cardiac failure defined as class IV in New York Heart Assocation
  • 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 12 months duration of the study,
  • Patients with EGPA who have already been treated with rituximab within the previous 12 months,
  • Patients with hypersensitivity to a monoclonal antibody or biologic agent,
  • Patients with contraindication to use rituximab, cyclophosphamide, mesna or azathioprine,
  • 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 that 3 times the upper limit of normal that cannot be attributed to underlying EGPA disease,
  • Patients unable to give written informed consent prior to participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02807103


Contacts
Contact: Benjamin TERRIER, MD, PhD +33 1 58 41 14 61 benjamin.terrier@aphp.fr
Contact: Severine POIGNANT +33 1 58 41 12 11 severine.poignant@aphp.fr

Locations
France
Hôpital Cochin Recruiting
Paris, France, 75014
Contact: Benjamin TERRIER, MD, PhD    +33 1 58 41 14 61    benjamin.terrier@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
French Vasculitis Study Group (FVSG)
Investigators
Study Chair: Xavier PUECHAL, MD, PhD Centre de référence " Maladies systémiques et autoimmunes rares, en particulier Vascularites nécrosantes et Sclérodermies systémiques "

Additional Information:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02807103     History of Changes
Other Study ID Numbers: P140915
2016-000275-25 ( EudraCT Number )
First Posted: June 21, 2016    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Rituximab
remission induction
eosinophilic granulomatosis with polyangiitis

Additional relevant MeSH terms:
Churg-Strauss Syndrome
Systemic Vasculitis
Granulomatosis with Polyangiitis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Immune System Diseases
Granuloma
Lymphoproliferative Disorders
Lymphatic Diseases
Cyclophosphamide
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists