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

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00281294
• Other study ID #: ZAF-711
• Status: Terminated
• Phase: Phase 2
• First received: January 20, 2006
• Last updated: August 2, 2008
• Start date: December 2005
• Est. completion date: December 2006

Study information

• Verified date: August 2008
• Source: Facet Biotech
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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).

Stage B of this trial is Double blind.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Fontolizumab

Locations

Country	Name	City	State
United States	The Center for Rheumatology	Albany	New York
United States	Rheumatology Associates Clinical Research	Chicago	Illinois
United States	Coeur d Alene Arthritis Clinic	Coeur d Alene	Idaho
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Justus J. Fiechtner MD PC	Lansing	Michigan
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	Stanford University Medical Center-Div. of Rheumatology	Palo Alto	California
United States	Benaroya Research Institute at Virginia Mason	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
PDL BioPharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	-Proportion of subjects achieving an American College of Rheumatology response (ACR50) at Week 14 (Stage A).
Secondary	Proportion of subjects achieving ACR20, ACR50, and ACR70 (Stages A and B)
Secondary	Change from baseline in serum CRP values (Stages A and B)
Secondary	Percent improvement in individual ACR core outcome measures (Stages A and B)
Secondary	Change from baseline in DAS28-CRP and ACR-N (Stages A and B)
Secondary	ACR-N at each dosing day and at 1 and 3 months after the last dose of study drug (Stages A and B)
Secondary	Number and proportion of subjects experiencing a disease flare-up since Week 14 (Stage B)
Secondary	Time to disease flare since Week 14 (Stage B)
Secondary	Assess the safety and tolerability of fontolizumab throughout the study by collection of the following:
Secondary	Adverse events and SAEs up to 84 days after last dose of study drug; and, opportunistic or medically significant infections, malignancies, and onset of autoimmune diseases up to 6 months after last dose of study drug
Secondary	Clinical laboratory measurements (hematology, serum chemistry) up to 84 days after last dose of study drug
Secondary	Evaluation of pharmacokinetics (PK) up to 6 months after last dose of study drug (Stages A and B)
Secondary	Evaluation of immunogenicity up to 6 months after last dose of study drug (Stages A and B)

External Links

•   Link