A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab

Study Description

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Brief Summary:

Rituximab 1000 mg i.v. will be given on day 1 and 15, week 26 - 28, together with a corticosteroid regimen consisting of methylprednisolone 100 mg i.v. 30 minutes prior to both infusions.

Condition or disease	Intervention/treatment	Phase
Early and Severe Systemic Sclerosis	Drug: Administration of rituximab and methylprednisolone	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Protocol Based Treatment for Early and Severe Systemic Sclerosis With (Anti-CD20), Rituximab
Study Start Date :	November 2006
Estimated Primary Completion Date :	August 2015
Estimated Study Completion Date :	August 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Administration of rituximab and methylprednisolone	Drug: Administration of rituximab and methylprednisolone; Rituximab: Pharmaceutical form: Concentrate for solution for infusion. Maximum duration of treatment: 28 weeks Maximum dose allowed: 2000 mg (use of total dose) Route of administration: intravenous use.

Outcome Measures

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Primary Outcome Measures :

1. Death [ Time Frame: 28 weeks ]
2. Heart failure defined as a LVEF< 30% [ Time Frame: 28 weeks ]
3. Lung failure defined as a resting PaO2< 60mmHg [ Time Frame: 28 weeks ]
4. Evolution of antibody titers. [ Time Frame: 28 weeks ]
5. Deterioration, improvement or stabilisation of, disease activity score, 6-m walking distance, SHAQ, LVEF and creatinine clearance [ Time Frame: 28 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• male or female >= 18 years
• SSc according to the ARA criteria for systemic sclerosis
• Disease duration less than 4 years (from the appearance of skin changes (oedema, fibrosis)
• Inadequate response to methotrexate (at least 12 weeks 10 mg/w, except if not tolerated
• Antibodies specific for systemic sclerosis: anti-topoisomerase; anti-centromere antibodies
• Severe disease defined by either one of the following: a modified Rodnan skin score (TSS° >= 14 ), disease activity score >= 3
• Contraception for women with childbearing potential. Sexual abstinence is an alternative to contraception.
• Patient has signed informed consent.

Exclusion Criteria:

• disease duration more than 4 years
• FVC <= 50%
• LVEF <= 40% of predicted value
• DLCO <= 40% of predicted value
• Lack of peripheral venous access
• Pregnancy or breast feeding
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease), evidence of significant uncontrolled concomitant disease such as, but not limited to, nervous system, renal, hepatic, endocrine or gastrointestinal disorders which, in the investigator's opinion, would preclude patient participation
• Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
• Known active infection of any kind (excluding fungal infections of mail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to baseline.
• History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis) within 52 weeks prior to baseline.
• History of serious recurrent or chronic infection (for screening for a chest infection a chest radiograph will be performed at screening if not performed within 12 weeks prior to screening).
• History of cancer, including solid tumors, hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinoma of the skin that have been excised and cured).
• History of a severe allergic or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of rituximab or to murine proteins.
• Concurrent treatment with any biologic agent or DMARD other than MTX. Treatment must be discontinued 14 days prior to baseline , except for the following: azathioprine for ≥ 28 days; leflunomide for ≥ 8 weeks (or ≥ 14 days after 11 days of standard cholestyramine or activated charcoal washout); infliximab ≥ 8 weeks; adalimumab ≥ weeks.
• Previous treatment with > 1 biological agent.
• Previous treatment with any cell depleting therapies, including investigational agents.
• Treatment with any investigational agent within 28 days of baseline or 5 half-lives of the investigational drug (xhich ever is the longer).
• Receipt of any vaccine within 28 days prior to baseline
• Intolerance or contraindications to i.v. glucocorticoids.
• Positive serum human chorionic gonadotropin (hCG) measured at screening or a positive pregnancy test prior to the first rituximab infusion.
• Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology.
• Hemoglobin < 8.0 g/dL.
• Concentrations of serum IgG and/or IgM below 5.0 and 0.40 mg/mL, respectively.
• Absolute neutrophil count (ANC) < 1.5 X 10³/µL.

Contacts and Locations

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Locations

Belgium
UCL St. Luc Brussel
Brussel, Belgium
UZ Brussel
Brussel, Belgium
University Hospital Ghent
Ghent, Belgium, 9000
UZ Gasthuisberg Leuven
Leuven, Belgium

Sponsors and Collaborators

University Hospital, Ghent

Investigators

Principal Investigator:	Filip De Keyser, MD, PhD	University Hospital, Ghent

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Website University Hospital Ghent 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Melsens K, De Keyser F, Decuman S, Brusselle G, De Pauw M, Deschepper E, De Wilde K, Elewaut D, Piette Y, Vandecasteele E, Smith V. Assessment of sensitivity to change of the European Scleroderma Study Group activity index. Clin Exp Rheumatol. 2016 Sep-Oct;34 Suppl 100(5):148-151. Epub 2016 Jul 18.

Smith V, Pizzorni C, Riccieri V, Decuman S, Brusselle G, DE Pauw M, Deschepper E, Piette Y, Ruaro B, Sulli A, Vandecasteele E, Melsens K, DE Keyser F, Cutolo M. Stabilization of Microcirculation in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement following Rituximab Treatment: An Open-label Study. J Rheumatol. 2016 May;43(5):995-6. doi: 10.3899/jrheum.151018.

Bonroy C, Smith V, Deschepper E, De Keyser F, Devreese K. Specific Antinuclear Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis Are Associated with Improvement of Skin Thickening. J Rheumatol. 2016 Jan;43(1):247-9. doi: 10.3899/jrheum.150105. Erratum in: J Rheumatol. 2016 Mar;43(3):681.

Smith V, Piette Y, van Praet JT, Decuman S, Deschepper E, Elewaut D, De Keyser F. Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. J Rheumatol. 2013 Jan;40(1):52-7. doi: 10.3899/jrheum.120778. Epub 2012 Nov 1.

Smith V, Van Praet JT, Vandooren B, Van der Cruyssen B, Naeyaert JM, Decuman S, Elewaut D, De Keyser F. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010 Jan;69(1):193-7. doi: 10.1136/ard.2008.095463.

Responsible Party:	University Hospital, Ghent
ClinicalTrials.gov Identifier:	NCT00379431 History of Changes
Other Study ID Numbers:	2006/257
First Posted:	September 21, 2006
Last Update Posted:	December 5, 2014
Last Verified:	December 2014

Additional relevant MeSH terms:

Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Rituximab; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Methylprednisolone acetate; Methylprednisolone; Prednisolone hemisuccinate; Prednisolone phosphate; Antineoplastic Agents	Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Hormonal