Rituxan With or Without Methotrexate in Psoriatic Arthritis

Phase IB, Investigator-Initiated, Open-Label, Multi-Center Trial of Rituximab With or Without Methotrexate In Subjects With Psoriatic Arthritis and Psoriasis

The purpose of this study is to help determine the effectiveness of rituxan (with or without methotrexate) in the treatment of psoriatic arthritis.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Drug: Rituximab

Detailed Description

The purpose of this study is to evaluate safety and efficacy of rituximab, with and without methotrexate, in joints, enthesium and skin in psoriatic arthritis patients with inadequate response to methotrexate who have either not tried anti-TNF therapy or have had inadequate or failed response to anti-TNF therapy. To explore biologic mechanism of action via histological and immunohistochemical evaluation of pre and post treatment biopsies of psoriatic plaques.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037-0943
      • University of California, San Diego
    • Stanford, California, United States, 94305-5350
      • Stanford University
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Rheumatology Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active disease of at least 6 months duration.
• Receiving treatment on an outpatient basis.
• The patient will have at least one evaluable skin plaque, 2 cm in diameter, that can be followed with a target lesion score (scalp and groin lesions cannot be used).
• Presence of PsA per the CASPAR categories: Psoriasis, Nail Changes, Negative RF test, Dactylitis or radiological evidence of juxta-articular new bone formation.
• Subjects will have greater than or equal to 3 tender (out of 68 joints) and 3 swollen (out of 66) joints at screening and baseline.

Exclusion Criteria:

• History of malignancy other than resolved squamous or basal cell or cervical carcinoma
• Presence of a significant medical illness that, in the opinion of the investigator, would potentially compromise the subject's ability to participate in the trial
• Presence of another rheumatic or skin disease that, in the opinion of the investigator, could confound the ability to discern response
• History or presence of HIV
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of recurrent significant infection or history of recurrent bacterial infections
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
• History of psychiatric disorder that, in the judgment of the investigator, would make the patient inappropriate for entry into this trial or would lead to poor compliance.
• Concurrent treatment with any DMARD (except for MTX), any anti-TNF alpha therapy or other biologic therapy. Topical medications to treat psoriasis are limited to class VI and VII low potency steroids to the palms, soles of the feet, axilla and groin only.
• Concurrent treatment with any DMARD (except for MTX), any anti-TNF alpha therapy or other biologic therapy. Topical medications to treat psoriasis are limited to class VI and VII low potency steroids to the palms, soles of the feet, axilla and groin only.
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
• Previous treatment with any cell-depleting therapies, including investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19).
• Previous treatment within 6 months with i.v. gamma-globulin, Orencia, toclizumab, natalizumab or Prosorba Column.
• Intra-articular or parental corticosteroid injections within 4 weeks prior to screening.
• Previous treatment with rituximab (MabThera/Rituxan)
• Immunization with a vaccine within 4 weeks prior to randomization (e.g.; MMR, Varivax, Smallpox).
• One intra-articular steroid joint injection is allowed, affected joint is excluded from assessment thereafter.
• Subjects should not take analgesics within 12 hours prior to joint assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of Rituximab in PSA and psoriasis by determining incidence of treatment emergent AE's including infections, infusion reactions and disease progression.	followed out for one year from last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
The exploration of efficacy of rituximab in PsA will be determined by using the week 24 ACR 20 measurement as modified for PsA using 68/66 tender/swollen joint count.	Week 24

Collaborators and Investigators

• Sponsor: Swedish Medical Center
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Philip J Mease, MD, Seattle Rheumatology Associates/ Swedish Research Center

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: July 27, 2007
• First Submitted That Met QC Criteria: July 30, 2007
• First Posted (Estimate): July 31, 2007

Study Record Updates

• Last Update Posted (Estimate): January 18, 2012
• Last Update Submitted That Met QC Criteria: January 16, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Arthritis; Psoriatic Arthritis; Rituxan; Rituximab
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: U3081n