A Phase 2 Study to Evaluate the Safety, Tolerability, and Activity of Fontolizumab in Subjects With Active Rheumatoid Arthritis

PDL BioPharma

Status and phase

Terminated

Phase 2

Conditions

Arthritis, Rheumatoid

Treatments

Drug: Fontolizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT00281294

ZAF-711

Details and patient eligibility

About

To evaluate the efficacy of fontolizumab in subjects with active rheumatoid arthritis as determined by a 50% improvement of an American College of Rheumatology criteria (ACR50) response at Week 14 (Stage A of study).

Full description

Stage B of this trial is Double blind.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female, at least 18 years of age
A diagnosis of RA according to ACR criteria (Appendix D, American College of Rheumatology Clinical Classification Criteria for Rheumatoid Arthritis)
RA functional class I, II, or III (Appendix E, ACR Revised Criteria for Classification of Functional Status in Rheumatoid Arthritis ) for at least 6 months
Active RA with ≥ 6 tender joints and ≥ 6 swollen joints within one week of dosing or on Day 0, before dosing
Serum CRP ≥ 1.0 mg/dL (10 mg/L) or ≥ 45 minutes of morning stiffness
On stable doses for at least 30 days before receiving study drug of at least one, but not more than two, of the following disease-modifying antirheumatic drugs (DMARDs): hydroxychloroquine, leflunomide, methotrexate (leflunomide-methotrexate combination is unacceptable), or sulfasalazine. If being treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose prednisone (≤ 10 mg/day), must be on stable regimen for at least 14 days before receiving study drug
Women of childbearing potential with a negative serum pregnancy test at screening
Subjects with reproductive potential agree to use a double-barrier method of contraception during the study and for 3 months after receiving last dose of study drug
Must provide a signed and dated informed consent and an authorization to use protected health information, have the ability to understand the study requirements, and comply with study procedures, including required study visits

Exclusion criteria

Significant involvement of secondary RA (eg, Felty's syndrome, pulmonary fibrosis, Sjogren's syndrome, vasculitis (keratoconjunctivitis sicca is not exclusionary)
Received a live vaccine within 30 days of receiving fontolizumab
Received an investigational agent within 30 days or five half-lives of the agent, whichever is longer, of receiving fontolizumab
Received a corticosteroid injection into any joint, or has been treated with > 10 mg/day of a corticosteroid within 30 days of receiving fontolizumab
Received etanercept or anakinra within 30 days of receiving fontolizumab
Received gold salts, infliximab, or adalimumab within 60 days of receiving fontolizumab
Received IV gamma-globulin or Prosorba column therapy within 90 days of receiving fontolizumab
Received rituximab or cyclophosphamide within 6 months of receiving fontolizumab
Failed B cell recovery after exposure to rituximab
History of hypersensitivity to glycine, histidine, or Polysorbate 80
Pregnant women or nursing mothers
Malignancy within 5 years (excluding basal or squamous cell carcinoma of the skin or adequately treated cervical carcinoma in situ)
Known chronic viral infections with HIV, hepatitis B, or hepatitis C
Clinical, PPD, or clear radiographic evidence of prior TB
Infection requiring hospitalization or parenteral medication, such as an antibiotic, antiviral, antifungal, or antiparasitic agent, within 90 days of receiving fontolizumab
History of inflammatory joint disease (eg, gout, Lyme disease, psoriatic arthritis, reactive arthritis, seronegative spondyloarthropathy) or chronic inflammatory diseases (eg, inflammatory bowel disease, inflammatory myopathy, multiple sclerosis, overlap syndrome, scleroderma, systemic lupus erythematosus) other than RA
Clinically significant unstable or poorly controlled acute or chronic diseases, such as myocardial infarction within 6 months, unstable angina, poorly controlled diabetes or hypertension
ALT > 1.5 × the upper limit of normal; AST > 1.5 × the upper limit of normal; creatinine 1.5 × the upper limit of normal; absolute neutrophil count (ANC) < 1000/mm3; platelet count < 50,000/mm3
History of any other medical disease, laboratory abnormalities, or psychological conditions that would make the subject (based upon the principal investigator's judgment) unsuitable for study enrollment
Current abuse of alcohol or drugs (based upon investigator's assessment)
Major surgery within 3 months prior to or planned elective surgery during or within 3 months after last dose of study drug