Baminercept, a Lymphotoxin-Beta Receptor Fusion Protein, for Treatment of Sjögren's Syndrome

Exclusion Criteria

• •Has an active infection excluding superficial cutaneous fungal or viral infections;
• •Has a chronic or persistent infection that might be worsened by immunosuppressive treatment (e.g., human immunodeficiency virus \[HIV\], hepatitis B, hepatitis C, or tuberculosis);
• •History of TB or positive intradermal skin test for purified protein derivative (PPD); positive Mantoux test defined as 10 mm of induration (size of raised bump, not redness), or equivalent positive TB test result, as per country clinical standards, during the screening period. Subjects whose PPD induration is ≥ 5 mm but \< 10 mm are eligible for the study if they had a negative chest x-ray during the screening period. There must be no other clinical evidence of TB on physical examination of the subject. Note: Subjects who have had prior adequate prophylaxis treatment for latent TB with an appropriate course of isoniazid or equivalent, per country standards, are not excluded from study participation. PPD should not be administered within 6 weeks of a live-virus vaccine;
• •History of recurrent significant infections or occurrence of a serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia) within twelve weeks prior to Day 0;
• •Receipt of live vaccine within six weeks prior to Day 0;
• •History or presence of primary or secondary immunodeficiency;
• •History of any life-threatening allergic reactions;
• •Is a pregnant or nursing female;
• •Ongoing anticoagulant therapy, which is a contraindication for labial salivary biopsy or tonsil biopsy;
• •Concurrent use of anticholinergic agents, such as tricyclic antidepressants, antihistamines, phenothiazines, antiparkinsonian drugs, anti-asthmatic medications, or gastrointestinal (GI) medications that cause xerostomia in more than 10% of patients;
• •Treatment with any of the following within the defined period prior to Screening:
• •* 2 years for rituximab;
• •* 24 weeks for cyclophosphamide;
• •* 8 weeks for azathioprine, cyclosporine, methotrexate, or mycophenolate mofetil;
• •* 4 weeks for intravenous immunoglobulin;
• •* 4 weeks for etanercept;
• •* 8 weeks for adalimumab;
• •* 12 weeks for infliximab.
• •Prednisone (or equivalent corticosteroid) \> 10 mg/day;
• •A definite diagnosis of RA, SLE, systemic sclerosis, or dermatomyositis;
• •A history of alcohol or substance abuse within 12 months of the screening visit;
• •A history of head and neck radiation therapy, sarcoidosis, or graft-versus-host disease;
• •A history of malignancy, except for a resected basal or major squamous cell carcinoma, cervical dysplasia, or in situ cervical cancer Grade I, within the last five years;
• •Severe pulmonary disease as manifested by one of the following at Screening:
• •* Resting oxygen saturation \< 92%;
• •* Force vital capacity (FVC) \< 50% predicted;
• •* Diffusion lung capacity for carbon monoxide (DLCO) \< 50%;
• •Abnormal laboratory results for the following parameters at the screening visit:
• •* Absolute neutrophil count (ANC): \< 1,500/mm\^3;
• •* Platelets: \< 100,000/mm\^3;
• •* Hemoglobin: \< 9 grams (g)/deciliter (dL);
• •* Serum creatinine: ≥ 2.0 mg/dL;
• •* AST: \> 1.5x upper limit of normal, or
• •* ALT: \> 1.5x upper limit of normal.
• •A psychiatric disorder rendering the subject incapable of providing informed consent;
• •Plans for foreign travel to countries other than Canada or Western Europe within the treatment period;
• •Inability or unwillingness to follow the protocol;
• •Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial;
• •Rochester substudy subjects who meet the following criteria are disqualified from enrolling in the tonsil biopsy substudy if they:
• •* Have any side effects to local anesthetics (e.g., lidocaine);
• •* Have any side effects to silver nitrate;
• •* Do not have tonsils;
• •* Are not able to go 48 hours without any NSAIDS;
• •* Are not able to go 2 weeks without acetylsalicylic acid (aspirin).