Rituximab in Systemic Sclerosis

Phase 2

Completed

• Conditions: Systemic Sclerosis
• Interventions: Drug: Placebo (NaCl); Drug: Rituximab

• Registration Number: NCT01748084
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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 Timeline

• Study First Submitted: 2012-12-10
• Study First Submitted QC: 2012-12-11
• Study First Posted: 2012-12-12
• Study Start: 2013-04-09
• Primary Completion: 2016-04-18
• Study Completion: 2016-04-18
• Status Verified: 2018-02
• Last Update Submitted: 2018-03-01
• Last Update Posted: 2018-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NaCl	Placebo (NaCl)	NaCl 500 ml IV day 1 and day 15 plus 100 mg methylprednisolone
Rituximab	Rituximab	Rituximab 1G IV day 1 and day 15 plus 100 mg methylprednisolone

Primary Outcome Measures

Name	Time	Method
Number of tender and swollen joints	at 6 months	Measured out of 53 joints

Secondary Outcome Measures

Name	Time	Method
Scleroderma	at 6 and 12 months	modified Rodnan skin score
Lung fibrosis	at 6 and 12 months	Pulmonary functional tests
Quality of life: SSc-HAQ	at 6 and 12 months	Validated scores
Quality of life: Duruöz index	at 6 and 12 months	Validated scores
Quality of life: SF-36	at 6 and 12 months	Validated scores

Trial Locations

Locations (1)

Cochin Hospital; 🇫🇷 Paris, France