| Eligibility |
Inclusion Criteria:
- (Fe) male >, = 18 years
- Fibrosing skin disorder, not fulfilling the ACR criteria for diffuse SSc
- Inadequate response to methotrexate (at least 12 weeks 10 mg/w, except if not
tolerated or contra-indicated
- Debilitating disease defined by either one of the following:
- Restriction of mobility
- Disfiguration: eg: facial involvement
- Severe Internal Organ involvement
- Contraception for women with childbearing potential. Sexual abstinence is an
alternative to contraception.
Exclusion Criteria:
- FVC<, = 50%
- LVEF<, = 40% of predicted value,
- DLCO<, = 40% of predicted value
- Exclusion criteria as specifically described in the protocol for anti-CD-20:
- 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.
- Treatment with any investigational agent within 28 days of baseline or 5 half-lives of
the investigational drug (which 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.
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