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Rituximab in Systemic Sclerosis (RECOVER)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01748084
Recruitment Status : Completed
First Posted : December 12, 2012
Last Update Posted : March 2, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE December 10, 2012
First Posted Date  ICMJE December 12, 2012
Last Update Posted Date March 2, 2018
Actual Study Start Date  ICMJE April 9, 2013
Actual Primary Completion Date April 18, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2012)
Number of tender and swollen joints [ Time Frame: at 6 months ]
Measured out of 53 joints
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2013)
  • Quality of life: SSc-HAQ [ Time Frame: at 6 and 12 months ]
    Validated scores
  • Scleroderma [ Time Frame: at 6 and 12 months ]
    modified Rodnan skin score
  • Lung fibrosis [ Time Frame: at 6 and 12 months ]
    Pulmonary functional tests
  • Quality of life: SF-36 [ Time Frame: at 6 and 12 months ]
    Validated scores
  • Quality of life: Duruöz index [ Time Frame: at 6 and 12 months ]
    Validated scores
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2012)
  • Quality of life: SSc-HAQ, SF-36, Duruöz index [ Time Frame: at 6 and 12 months ]
    Validated scores
  • Scleroderma [ Time Frame: at 6 and 12 months ]
    modified Rodnan skin score
  • Lung fibrosis [ Time Frame: at 6 and 12 months ]
    Pulmonary functionnal tests
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab in Systemic Sclerosis
Official Title  ICMJE Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis
Brief Summary The purpose of this study is to determine whether rituximab is effective in the treatment of articular symptoms that occur in systemic sclerosis related polyarthritis
Detailed Description

Systemic sclerosis (SSc) is a rare disease, characterized by microvascular and immunological changes promoting extra-cellular matrix synthesis and widespread fibrosis. No treatment has yet proven any ability to alter the disease fibrosing process. Specific auto-antibodies are commonly found in this disease, and B lymphocytes are detected in cutaneous and pulmonary infiltrates. Studies derived from murine models suggest a role for B lymphocyte blocking strategies.

This lead to observational trials of B-cell therapy using rituximab in SSc that provided encouraging results with no particular signal concerning tolerability. These trials included heterogeneous patients with variable disease stages and different involved organs, and were mostly unblinded, which preclude any definitive conclusion. However, they support the continuous development of this therapeutic approach.

Taking up the early phase of the diffuse form of the disease is complicated by its rarity and the heterogeneous progression of its visceral complications. This raises the question of selecting a homogeneous group of patients to evaluate. The most convincing results for the use of rituximab in autoimmune conditions have been found in rheumatoid arthritis. Joint involvement is common in SSc with 75% of patients complaining about joint stiffness and pain, and 30% presenting with synovitis, tenosynovitis, or flexion contractures. No specific treatment has already addressed this issue, and it is generally proposed to use small doses of oral corticosteroids in association with methotrexate, by analogy with rheumatoid arthritis. We propose to evaluate the efficacy and safety of rituximab in SSc patients having active arthritis despite first line treatment. Improving the articular involvement would improve the quality of life f SSc patients and effectiveness of rituximab on skin and lung fibrotic involvements will be assessed as secondary outcomes to estimate the overall effects of this drug on SSc.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Systemic Sclerosis
Intervention  ICMJE
  • Drug: Rituximab
    Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone
  • Drug: Placebo (NaCl)
    Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone
Study Arms  ICMJE
  • Placebo Comparator: NaCl
    NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone
    Intervention: Drug: Placebo (NaCl)
  • Experimental: Rituximab
    Rituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone
    Intervention: Drug: Rituximab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 20, 2015)
22
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2012)
90
Actual Study Completion Date  ICMJE April 18, 2016
Actual Primary Completion Date April 18, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Systemic sclerosis fulfilling ACR or LeRoy's criteria
  • Active polyarthritis defined by > 6/53 tender joints and > 4/53 swollen joints
  • Ongoing first line therapy by prednisone (max 10 mg/d) and DMARDS (methotrexate, leflunomide, azathioprine or mycophenolate)
  • Birth control if applicable

Exclusion Criteria:

  • Overlap syndrome defined by clinical symptoms and positive specific auto-antibodies (anti-CCP, anti-SSA, anti-DNA DNA anti-Sm) (Rheumatoid factors and anti-RNP are not exclusion criteria)
  • Past therapy with Rituximab.
  • Severe and uncontrolled disease with renal, liver or haematological (neutropenia < 1500 / mm3) failures, pulmonary (FVC < 50%) or cardiac insufficiencies (LVEF < 50%)
  • Not stable corticosteroid therapy or cyclophosphamide use in the last 6 months
  • Infectious risk : viral infections by B or C hepatitis or HIV, hypogammaglobulinemia (< 6 G/L), opportunistic infection or infection requiring IV antibiotics in the last 3 months.
  • Neoplastic solid tumor in the last 5 years
  • Drug or alcool abuses
  • Receiving patient or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01748084
Other Study ID Numbers  ICMJE P110110
2012-001636-56 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yannick Allanore, MD, PhD Assistance Publique Hôpitaux de Paris, Université Paris Descartes
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP