a study of amg 557 in adults with systemic lupus erythematosus

Conditions: Systemic Lupus Erythematosus

Summary: this is a phase 1, randomized, placebo-controlled, double-blind, dose-escalation study of repeat sc doses of amg 557 in adults with systemic lupus erythematosus.


Eligibility criteria:
inclusion criteria: * before any study-specific procedure, the appropriate written informed consent must be obtained; * men and women, between the ages of 18 and 70 years old, inclusive, at the time of randomization; * diagnosis of sle as defined by the most recent acr criteria, including a positive ana at screening or documented positive ana (the titer should be at least 1:80) in the past. * sle duration of at least six months, as diagnosed by a physician; * stable disease, defined as no change in sle therapy within the previous 30 days; and, in the opinion of the investigator, no anticipated need for a change in sle therapy will be required while the subject is enrolled in the study; * normal or clinically acceptable ecg (12-lead reporting ventricular rate and pr, qrs, qt, qtc) at screening and day -1 based on the opinion of the investigator; * body mass index from 18 to 40 kg/m2 at screening; * able and willing to complete entire study according to study schedule. * immunizations up to date, with a minimum of tetanus, diphtheria, pertussis (td/tdap), pneumococcal (polysaccharide) and influenza (during flu season) vaccinations, as determined by the principal investigator. exclusion criteria: * positive serology for hiv antibodies, hepatitis b surface antigen or hepatitis c antibodies (confirmed by pcr or riba); * have had signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization; * evidence of active or latent tuberculosis as assessed by ppd or quantiferon testing at screening; * have donated blood or experienced a loss of blood \>500ml within 4 weeks of randomization; * history of ethanol or drug abuse within the last one year prior to randomization; * evidence of significant renal insufficiency, defined by: the glomerular fitration rate \< 50 ml/min using the cockroft and gault equation; * evidence of liver disease (eg, serum alt or ast \> 2x upper limit of normal); * total wbc \<3000 x 106/l; * neutrophil count \< 1500 x106/l * platelet count \<75,000 x 106/l * hemoglobin \<10g/dl * any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of sle) that would, by it progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures in the medical judgment of the investigator. this includes any age related co-morbidites such as presence of congestive heart failure, angina, chronic obstructive pulmonary disease, asthma, and malignancies (other than resected squamous and basal cell carcinoma of the skin). * presence or history of vasculitis (comprising internal organs or extremities or leading to peripheral neuropathy) within the last 3 years, presence or history of active cns lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to sle , encephalitis, meningitis, and myelitis) requiring therapy within the last 3 years; * uncontrolled hypertension (blood pressure \> 150/95); * poorly controlled diabetes (hba1c \> 8%); * any history of granulomatous disease including autoimmune granulomatous vasculitis and sarcoidosis; * underlying condition that predisposes the subject to infections (eg, history of splenectomy); * any disorder or condition that prevents the subject from providing truly informed consent; * prior administration of any other biologic that primarily targets the immune system (eg, lymphostat-b, taci-ig, or ctla4-ig) in the past 9 months. this includes prior administration of amg 557; * presence of amg 557 anti-bodies; * prior administration of rituximab \> 9 months with cd19+ b cells \<5/µl; * administration of cyclophosphamide (or any other alkylating agent), cyclosporine, tacrolimus, or sirolimus, or \> 100 mg/day prednisone or equivalent in the 6 months prior to randomization; * participated in an investigational drug trial involving a monoclonal antibody (not targeting the immune system) within 3 months or 5 half-lives, whichever time period is longer, prior to randomization; * participated in any another investigational drug or device trial within the previous 30 days or 5 half-lives, whichever time period is longer, prior to randomization; * administration of \>10 mg/day prednisone (or equivalent) in the 30 days prior to randomization; * known sensitivity to mammalian derived products; * unwilling to practice an effective method of double-barrier contraception as determined by the investigator for the duration of the study; * positive serum hcg at screening or positive urine hcg on d-1; or females who are currently lactating; * known allergies to shellfish or any excipients found in klh; * previous immunization with klh.

Keywords: systemic lupus erythematosus icosl b7rp-1 costimulation