This is an open label study of Rituximab in patients with progressive sarcoidosis to assess
the safety and tolerability of Rituximab in this patient population. The length of the
study will be 52 weeks.
- Men and women > 18 years of age.
- Sarcoidosis diagnosed at least 1 year prior to screening.
- Histological proven sarcoidosis prior to screening.
- Have a diagnosis of severe sarcoidosis with evidence of parenchymal disease on chest
radiograph (Stage III) or abnormal PFT, with histologic and there should be an
evidence of sarcoid (involvement by biopsy ( pulmonary or extrapulmonary)) . Subjects
with concurrent extrapulmonary sarcoidosis particularly skin and eye involvement are
encouraged to be enrolled. Patients with neuro-sarcoidosis will be excluded.
- Have FVC > 40 and < 80% of predicted.
- Have an ATS dyspnea score of > Grade 1.
- Have been receiving pre-study treatment that includes at least 10 mg/day of
prednisone or equivalent dose of corticosteroids as a single agent, and/or
methotrexate, or hydroxychloroquine for at least the 3-month period prior to
screening. Subjects must be on a stable dose of these meds for > 4 weeks before
starting the study medication.
- Adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine
device, barrier method with spermicide, or surgical sterilization) must be used for
the duration of the study and should continue such precautions for 6 months after
receiving the last study infusion.
- Are considered eligible based on TB screening.
- Are capable of reading and understanding subject assessment forms and providing
written informed consent.
- Are willing and able to adhere to the study visit schedule and other
- Previous Treatment with Rituximab (MabThera® / Rituxan®)
- Previous administration of a treatment with any other therapeutic agent targeted at
depleting B cells within 12 months prior to screening.
- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives
of the investigational drug (whichever is longer)
- Current treatment with TNF inhibitors, cyclosporine, tacrolimus or leflunomide.•
Treatment with TNF inhibitors within (8 weeks prior to screening), cyclosporine or
tacrolimus ( 4 weeks prior to screening) or leflunomide ( 8 weeks prior to screening,
or 25 days after cholestyramine washout).
- Previous treatment within 6 months with IVIg.
- Parenteral corticosteroids within 4 weeks prior to screening visit.
- Receipt of live virus or bacterial vaccinations within the 4 weeks before the first
dose of the study agent or are expected to receive any live virus or bacterial
vaccinations during the trial or up to 3 months after the last dose of the study
- History of severe allergic or anaphylactic reactions associated with the
administration of humanized or murine monoclonal antibodies
- History of New York Heart Association (NYHA) Class III or IV congestive heart
- History of severe right-sided heart failure or cor pulmonale
- Known active bacterial, viral, fungal mycobacterial, or other infection (including
tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
nail beds) or any major episode of infection requiring hospitalization or treatment
with i.v. antibiotics within 2 months of screening or oral antibiotics within 2 weeks
prior to screening
- History of recurrent significant infection or history of recurrent bacterial
- History of opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus,
Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria
other than TB) within 6 months prior to screening
- History of known infection with human immunodeficiency virus (HIV)
- Considered ineligible according to the USA-specific TB screening
- Pregnancy (a negative serum pregnancy test should be performed for all women of
childbearing potential within 7 days of treatment) or lactation
- Current signs and symptoms of systemic lupus erythematosus, or severe, progressive,
or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac,
neurologic, or cerebral diseases (with the exception of sarcoidosis).
- Have normal pulmonary function
- Have any clinical evidence of intracranial lesions.
- Have an abnormal neurological examination during baseline assessment
- Have neurosarcoidosis
- Have a known history of demyelinating disease such as multiple sclerosis or optic
- Concomitant malignancies or previous malignancies, with the exception of adequately
treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the
- Have poor tolerability of intravenous infusion or lack of adequate venous access for
required blood sampling.
- History of transplanted organ (with the exception of a corneal transplant > 3 months
prior to screening.
- History of substance abuse or dependency, drug or alcohol within 3 years of screening
- History of primary or secondary immunodeficiency
- History of psychiatric disorder that would interfere with normal participation in
- Any other disease, metabolic dysfunction, physical examination finding, or
- clinical laboratory finding giving reasonable suspicion of a disease or condition
- that contraindicates the use of an investigational drug or that may affect the
- interpretation of the results or render the patient at high risk from treatment
- Inability to comply with study and follow-up procedures