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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: prednisone

Detailed Description

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..

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Research Of Florida, Inc.
    • Tampa, Florida, United States, 33612
      • University of South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: prednisone; Prednisone 40mg by mouth 30-60 minutes prior to rituximab.	Drug: prednisone; prednisone 40mg by mouth 30-60 minutes prior to rituximab; Other Names: Rayos

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Acute Infusion Reactions in the First 24 Hours After Oral Prednisone Pretreatment to Initial Rituximab Infusion	Open-label assessment of AIR's during and/or within 24 hours in patients pretreated with 40mg oral prednisone 30 minutes prior to initial rituximab infusion	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Infusion Reactions Within 24 Hours Following the Second Rituximab Infusion.	Assessment of all adverse infusion reactions within 24 hours of receipt of the second rituximab infusion	24 hours
Adverse Events Assessed From Day 15 Through Week 26.	All adverse events reported from day 15 (24 hours after second infusion) through week 26.	24 weeks

Collaborators and Investigators

• Sponsor: University of South Florida

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 24, 2007

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Rituxan; Rituximab
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: U4164s

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No