Rituximab in Systemic Sclerosis (RECOVER)

This study is currently recruiting participants.
Verified April 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01748084
First received: December 10, 2012
Last updated: August 1, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Systemic Sclerosis
Drug: Rituximab
Drug: Placebo (NaCl)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of tender and swollen joints [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    Measured out of 53 joints


Secondary Outcome Measures:
  • Quality of life: SSc-HAQ [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
    Validated scores

  • Scleroderma [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
    modified Rodnan skin score

  • Lung fibrosis [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
    Pulmonary functional tests

  • Quality of life: SF-36 [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
    Validated scores

  • Quality of life: Duruöz index [ Time Frame: at 6 and 12 months ] [ Designated as safety issue: No ]
    Validated scores


Estimated Enrollment: 90
Study Start Date: April 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: NaCl
NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone
Drug: Placebo (NaCl)
Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone
Experimental: Rituximab
Rituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone
Drug: Rituximab
Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01748084

Contacts
Contact: Yannick Allanore, MD, PhD +331 58412563 yannick.allanore@cch.aphp.fr
Contact: Laurence Lecomte, PhD +33 1 71 19 64 94 laurence.lecomte@nck.aphp.fr

Locations
France
Cochin Hospital Recruiting
Paris, France, 75014
Contact: Yannick Allanore, MD, PhD    +331 58412563    yannick.allanore@cch.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Yannick Allanore, MD, PhD Assistance Publique Hôpitaux de Paris, Université Paris Descartes
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01748084     History of Changes
Other Study ID Numbers: P110110, 2012-001636-56
Study First Received: December 10, 2012
Last Updated: August 1, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Systemic sclerosis
Arthritis
B-cell therapy, Anti-CD20 therapy
Quality of life
Scleroderma
Lung fibrosis
Randomised controled trial

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Rituximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014