A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT00580229
First received: December 18, 2007
Last updated: July 16, 2012
Last verified: July 2012
  Purpose

This study will be an open-label prospective analysis of oral prednisone (compared to IV methylprednisolone) as a pre-treatment for rituximab in patients with rheumatoid arthritis. The study will be useful as pilot data to establish that there are no different trends between the two treatment strategies at decreasing the frequency and severity of acute infusion reactions. It would also establish proof of principle that pre-treatment with oral prednisone is equally as efficacious as IV methylprednisolone.

The primary endpoint will be to assess the safety and tolerability of rituximab (Rituxan) in RA.

By showing that there are no differences in the frequency or severity of acute infusion reactions after rituximab when using pre-treatment with oral prednisone compared to I.V. methylprednisolone, we will establish proof of principle that oral prednisone is a viable alternative to I.V. methylprednisolone. Pre-treatment with oral prednisone would be a practical advantage for both the patient and the treating physician. The patient could self-administer this treatment at home thereby decreasing the time they would need to spend at the infusion center. Further, this dose of prednisone has fewer side effects than 100mg of methylprednisolone.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: prednisone
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • The primary endpoint will be to assess the safety and tolerability of rituximab (Rituxan) in RA. This will be determined by assessing all acute infusion reactions in the first 24 hours following the patient's very first infusion (i.e. at baseline). [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • All adverse events (AE's) within 24 hours following the first infusion. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • All acute infusion reactions with 24 hours following the second infusion. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • All AE's within 24 hours following the second infusion. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
  • All AE's through week 26. [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
  • HAQ-DI [ Time Frame: weeks 4, 8, 16, 26 ] [ Designated as safety issue: No ]
  • DAS-28 [ Time Frame: weeks 4, 8, 16, 26 ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: December 2007
Study Completion Date: December 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Prednisone 40mg by mouth 30-60 minutes prior to rituximab.
Drug: prednisone
prednisone 40mg by mouth 30-60 minutes prior to rituximab

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • American College of Rheumatology Criteria for Rheumatoid Arthritis
  • Age 18-80
  • Concomitant methotrexate (MTX) [oral or parenteral at any dose]
  • IgG & IgM levels above lower limit of normal.
  • Adequate renal function as indicated by serum creatinine of < or = 1.8
  • Study subjects can be either MTX-inadequate responders or TNF-alpha antagonists inadequate responders
  • Able and willing to give written informed consent and comply with the requirements of the study protocol
  • Negative serum pregnancy test (for women of child bearing age)
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
  • If patients are on corticosteroids, they must be on a dose of < or = to prednisone 10mg oral daily (or its equivalence) and the dose must remain stable for 4 weeks prior to their first rituximab infusion.

Exclusion Criteria:

  • An inflammatory arthritis other than RA
  • ANC < 1.5 x 103
  • Hemoglobin: < 8.0 gm/dL
  • Platelets: < 100,000/mm
  • AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
  • Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
  • History of positive HIV (HIV conducted during screening if applicable)
  • Treatment with any TNF-alpha antagonist within 8 weeks of Day 1 visit (for infliximab and adalimumab) or 4 weeks (for etanercept).
  • Previous treatment with abatacept (Orencia) at any time.
  • Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
  • Receipt of a live vaccine within 4 weeks prior to randomization
  • Previous Treatment with Rituximab (MabThera® / Rituxan®)
  • Previous treatment with Natalizumab (Tysabri®)
  • 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
  • Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4 weeks
  • Lack of peripheral venous access
  • History of drug, alcohol, or chemical abuse within 6 months prior to screening
  • Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
  • Concomitant malignancies or previous malignancies within 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • History of psychiatric disorder that would interfere with normal participation in this protocol
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Inability to comply with study and follow-up procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00580229

Locations
United States, Florida
Arthritis Research of Florida, Inc.
Palm Harbor, Florida, United States, 34684
University of South Florida
Tampa, Florida, United States, 33612
Sponsors and Collaborators
University of South Florida
Investigators
Principal Investigator: John D. Carter, M.D. University of South Florida
  More Information

No publications provided

Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT00580229     History of Changes
Other Study ID Numbers: U4164s, 6173-A673CA
Study First Received: December 18, 2007
Last Updated: July 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of South Florida:
Rituxan
Rituximab

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Rituximab
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014