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

Study Description

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Brief 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).

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid	Drug: Fontolizumab	Phase 2

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2 Study to Evaluate the Safety, Tolerability, and Activity of Fontolizumab in Subjects With Active Rheumatoid Arthritis
Study Start Date :	December 2005
Study Completion Date :	December 2006

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. -Proportion of subjects achieving an American College of Rheumatology response (ACR50) at Week 14 (Stage A).

Secondary Outcome Measures :

1. Proportion of subjects achieving ACR20, ACR50, and ACR70 (Stages A and B)
2. Change from baseline in serum CRP values (Stages A and B)
3. Percent improvement in individual ACR core outcome measures (Stages A and B)
4. Change from baseline in DAS28-CRP and ACR-N (Stages A and B)
5. ACR-N at each dosing day and at 1 and 3 months after the last dose of study drug (Stages A and B)
6. Number and proportion of subjects experiencing a disease flare-up since Week 14 (Stage B)
7. Time to disease flare since Week 14 (Stage B)
8. Assess the safety and tolerability of fontolizumab throughout the study by collection of the following:
9. 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
10. Clinical laboratory measurements (hematology, serum chemistry) up to 84 days after last dose of study drug
11. Evaluation of pharmacokinetics (PK) up to 6 months after last dose of study drug (Stages A and B)
12. Evaluation of immunogenicity up to 6 months after last dose of study drug (Stages A and B)

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, California
Wallace Rheumatic Study Center
Los Angeles, California, United States, 90048
Stanford University Medical Center-Div. of Rheumatology
Palo Alto, California, United States, 94304
United States, Colorado
Denver Arthritis Clinic
Denver, Colorado, United States, 80230
United States, Idaho
Coeur d Alene Arthritis Clinic
Coeur d Alene, Idaho, United States, 83814
United States, Illinois
Rheumatology Associates Clinical Research
Chicago, Illinois, United States, 60612
United States, Michigan
Justus J. Fiechtner MD PC
Lansing, Michigan, United States, 48910-8595
United States, New York
The Center for Rheumatology
Albany, New York, United States, 12206
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
United States, Washington
Benaroya Research Institute at Virginia Mason
Seattle, Washington, United States, 98101

Sponsors and Collaborators

PDL BioPharma, Inc.

Investigators

Principal Investigator:	Mark C. Genovese, MD	Stanford University Medical Center-Div. of Rheumatology
Principal Investigator:	Jerry Molitor, MD, PhD	Benaroya Research Institute at Virginia Mason
Principal Investigator:	Michael H. Schiff, MD	Denver Arthritis Clinic
Principal Investigator:	Alan Kivitz, MD	Altoona Center for Clinical Research
Principal Investigator:	Craig Wiesenhutter, MD	Coeur d Alene Arthritis Clinic
Principal Investigator:	Justus J. Fiechtner, MD	Justus Fiechtner MD PC
Principal Investigator:	Daniel Wallace, MD	Wallace Rheumatic Study Center
Principal Investigator:	Joel Kremer, MD	The Center for Rheumatology
Principal Investigator:	Robert S. Katz, MD	Rheumatology Associates Clinical Research

More Information

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Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wilson JA, Prow NA, Schroder WA, Ellis JJ, Cumming HE, Gearing LJ, Poo YS, Taylor A, Hertzog PJ, Di Giallonardo F, Hueston L, Le Grand R, Tang B, Le TT, Gardner J, Mahalingam S, Roques P, Bird PI, Suhrbier A. RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation. PLoS Pathog. 2017 Feb 16;13(2):e1006155. doi: 10.1371/journal.ppat.1006155. eCollection 2017 Feb.

ClinicalTrials.gov Identifier:	NCT00281294 History of Changes
Other Study ID Numbers:	ZAF-711
First Posted:	January 24, 2006
Last Update Posted:	August 5, 2008
Last Verified:	August 2008

Keywords provided by Facet Biotech:

Arthritis, Rheumatoid

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases	Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases