Clinical trial NCT00580229: A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis.
Official title: A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Rituxan
Rituximab
Lead sponsor: University of South Florida
Sponsor class: OTHER
First posted: 2007-12-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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..

Eligibility 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

Primary outcomes:
measure: Number of Acute Infusion Reactions in the First 24 Hours After Oral Prednisone Pretreatment to Initial Rituximab Infusion
timeFrame: 24 hours
Secondary outcomes:
measure: Adverse Infusion Reactions Within 24 Hours Following the Second Rituximab Infusion.
timeFrame: 24 hours
measure: Adverse Events Assessed From Day 15 Through Week 26.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Palm Harbor
country: United States
facility: Arthritis Research of Florida, Inc.
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
Study officials:
affiliation: University of South Florida
name: John D. Carter, M.D.
role: PRINCIPAL_INVESTIGATOR
References: