Rituximab in Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— RECOVER  

Official title:

Evaluation of Rituximab in Systemic Sclerosis Associated Polyarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01748084
• Other study ID #: P110110
• Secondary ID: 2012-001636-56
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: December 10, 2012
• Last updated: March 1, 2018
• Start date: April 9, 2013
• Est. completion date: April 18, 2016

Study information

• Verified date: February 2018
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 18, 2016
• Est. primary completion date: April 18, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Rituximab
Days 1 and 15, rituximab 1 gramme plus 100 mg methylprednisolone
• Placebo (NaCl)
Days 1 and 15, NaCl 500 ml plus 100 mg methylprednisolone

Locations

Country	Name	City	State
France	Cochin Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

Bosello S, De Santis M, Lama G, Spanò C, Angelucci C, Tolusso B, Sica G, Ferraccioli G. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res Ther. 2010;12(2):R54. doi: 10.1186/ar2965. Epub 2010 Mar 25. — View Citation

Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Korfiatis P, Yiannopoulos G, Andonopoulos AP. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum. 2010 Oct;40(2):127-36. doi: 10.1016/j.semarthrit.2009.09.003. Epub 2009 Dec 11. Review. — View Citation

Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 2010 Feb;49(2):271-80. doi: 10.1093/rheumatology/kep093. Epub 2009 May 15. — View Citation

Lafyatis R, Kissin E, York M, Farina G, Viger K, Fritzler MJ, Merkel PA, Simms RW. B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):578-83. doi: 10.1002/art.24249. — View Citation

Simms RW, Lafyatis R. Rituximab: a potential therapeutic advance in scleroderma: what is the evidence? Rheumatology (Oxford). 2010 Feb;49(2):201-2. doi: 10.1093/rheumatology/kep421. Epub 2009 Dec 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of tender and swollen joints	Measured out of 53 joints	at 6 months
Secondary	Quality of life: SSc-HAQ	Validated scores	at 6 and 12 months
Secondary	Scleroderma	modified Rodnan skin score	at 6 and 12 months
Secondary	Lung fibrosis	Pulmonary functional tests	at 6 and 12 months
Secondary	Quality of life: SF-36	Validated scores	at 6 and 12 months
Secondary	Quality of life: Duruöz index	Validated scores	at 6 and 12 months