Safety, Efficacy and Pharmacokinetics of an Antibody for Psoriatic Arthritis

A phase II, randomized, double-blind, placebo-controlled study to:

• Demonstrate the clinical efficacy of efalizumab in the treatment of subjects with psoriatic arthritis (PsA).
• Evaluate the safety, tolerability and pharmacokinetics of efalizumab in the treatment of subjects with PsA

Inclusion criteria

• Diagnosed with PsA as defined by:

• Presence of psoriasis with at least one 2 cm plaque AND
• One of the five functional classifications of PsA
• Functional Class I, II, or III as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Moderate to severe disease, defined as follows:

• At least 3 tender and 3 swollen joints (78 joint count for tenderness and 76 joints for swelling; AND
• Either ESR ≥ 28 mm/hr, CRP ≥ 1.5 mg/dL, or morning stiffness for ≥ 30 minutes.
• Currently taking at least one of the following systemic therapies for PsA: pre-existing stable doses of NSAIDs, corticosteroids (≤ 10 mg/day), and either sulfasalazine (≤ 3 gm/day) or methotrexate (≥ 7.5 and ≤ 30 mg/week) but not both.
• 18 to 80 years of age.
• Body weight ≤ 125 kg (275 lbs).
• Candidate for systemic immunomodulatory therapy.
• Using an acceptable method of birth control.
• If female, must have a negative serum pregnancy test during screening period, must be surgically sterile, or must be at least five years postmenopausal.
• Informed about the study and signed an informed consent prior to performance of any study-related procedure.

Exclusion criteria

• Previous treatment with efalizumab.
• Rheumatoid Factor positive without dactylitis or positive X-rays of the hands or feet, or with rheumatoid nodules.
• History of joint replacement surgery within 60 days prior to the start of study drug dosing.
• Joint replacement therapy planned within nine months subsequent to the start of study drug dosing.
• Intra-articular cortisone injections within 28 days prior to the start of study drug dosing.
• Pregnancy or lactation.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Respiratory distress (dyspnea, oxygen desaturation with pO2 < 90% or onset of acute respiratory distress syndrome), flank or back pain, and/or hypotension may be signs of anaphylaxis.
• Active bacterial, viral, fungal, mycobacterium tuberculosis or atypical mycobacterium infection.
• Positive PPD test unless subject with positive PPD test completed a course of treatment for tuberculosis
• History of any opportunistic infection.
• History of a malignancy within the past five years. Subjects with a history of fully resolved, resected, basal or squamous cell carcinoma may be enrolled.
• Received any vaccine within 28 days prior to the start of study drug dosing.
• Chronic disorders apart from PsA affecting the joints, such as systemic lupus erythematosus, rheumatoid arthritis, gout, scleroderma or known reactive arthritis (e.g., Reiter's syndrome).
• COPD, asthma, or other pulmonary disease requiring more therapy than using one inhaler 4× daily.
• Failed to respond or maintain response to Enbrel.
• Received any DMARD other than methotrexate or sulfasalazine during the 28 days prior to the start of study drug dosing.
• Approved biologic PsA therapy during the 28 days or seven half-lives of the drug prior to the start of study drug dosing, whichever is the greater length of time; Enbrel within 42 days prior to the start of study drug dosing.
• Investigational drug and/or treatment during the 28 days or 7 half-lives of the drug prior to the start of study drug dosing, whichever is the greater length of time.
• Any condition which, in the opinion of the Investigator, would jeopardize the subject's safety following exposure to efalizumab.
• Liver disease (e.g., hepatitis, cirrhosis) or abnormal hepatic function (AST or ALT ≥ 2.5

• ULN).
• Serum creatinine level ≥ 1.5 mg/dL
• Platelet count ≤ 125,000 cells/mm3
• WBC count ≤ 3,500 cells/mm3
• Total lymphocyte count ≤ 1000 cells/mm3
• Seropositive for hepatitis B
• Seropositive for hepatitis C antibody
• Seropositive for HIV
• Antinuclear antibodies titer ≥ 1:80
• History of inflammatory bowel disease