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

• Sponsor: University of South Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT00580229
• Collaborator: (none)
• Enrollment: 50
• Locations: 2
• Arm: 1
• Duration (Months): 48
• Patients Per Site: 25
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: prednisone	Phase 2/Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Safety Analysis of Oral Prednisone as a Pre-Treatment for Rituximab in Rheumatoid Arthritis.
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Acute Infusion Reactions in the First 24 Hours After Oral Prednisone Pretreatment to Initial Rituximab Infusion [24 hours]

   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

Secondary Outcome Measures

1. Adverse Infusion Reactions Within 24 Hours Following the Second Rituximab Infusion. [24 hours]

   Assessment of all adverse infusion reactions within 24 hours of receipt of the second rituximab infusion

2. Adverse Events Assessed From Day 15 Through Week 26. [24 weeks]

   All adverse events reported from day 15 (24 hours after second infusion) through week 26.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Arthritis Research of Florida, Inc.	Palm Harbor	Florida	United States	34684
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of South Florida
• ClinicalTrials.gov Identifier: NCT00580229
• Other Study ID Numbers: U4164s
• First Posted: Dec 24, 2007
• Last Update Posted: Jul 26, 2018
• Last Verified: May 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of South Florida: Rituxan; Rituximab
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Prednisone

Study Results

Participant Flow

Recruitment Details	From February 2008 to January 2011 in the medical clinic.
Pre-assignment Detail	All study participants were treated with open-label standard dose and the recommended infusions of rituximab for rheumatoid arthritis.

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
Period Title: Overall Study
STARTED	50
COMPLETED	50
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
Overall Participants	50
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	48 96%
>=65 years	2 4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27 (28)
Sex: Female, Male (Count of Participants)
Female	48 96%
Male	2 4%
Region of Enrollment (participants) [Number]
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Number of Acute Infusion Reactions in the First 24 Hours After Oral Prednisone Pretreatment to Initial Rituximab Infusion
Description	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
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

The subjects were 18-80 years of age, and fulfilled the 1987 American College of Rheumatology Criteria for Rheumatoid Arthritis, and taking concomitant methotrexate.

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
Measure Participants	50
Number [acute infusion reactions]	50

2. Secondary Outcome

Title	Adverse Infusion Reactions Within 24 Hours Following the Second Rituximab Infusion.
Description	Assessment of all adverse infusion reactions within 24 hours of receipt of the second rituximab infusion
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
Measure Participants	48
Number [acute infusion reactions]	48

3. Secondary Outcome

Title	Adverse Events Assessed From Day 15 Through Week 26.
Description	All adverse events reported from day 15 (24 hours after second infusion) through week 26.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
Measure Participants	48
Number [events]	48

Adverse Events

Arm/Group Title	Oral Prednisone as a Pretreatment to Rituximab
Arm/Group Description	40mg of oral prednisone given 30 min prior to rituximab as a prophylaxis against acute infusion reactions(AIR), as an alternative to the intravenous methylprednisone as a pretreatment for rituximab.
All Cause Mortality
	Oral Prednisone as a Pretreatment to Rituximab
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	Oral Prednisone as a Pretreatment to Rituximab
	Affected / at Risk (%)	# Events
Total	3/50 (6%)
Cardiac disorders
atrial fibrillation	1/50 (2%)	1
Psychiatric disorders
suicide attempt	1/50 (2%)	50
Respiratory, thoracic and mediastinal disorders
asthma exacerbation	1/50 (2%)	50
Other (Not Including Serious) Adverse Events
	Oral Prednisone as a Pretreatment to Rituximab
	Affected / at Risk (%)	# Events
Total	32/50 (64%)
Gastrointestinal disorders
diarrhea	2/50 (4%)
nausea	2/50 (4%)
General disorders
headache	3/50 (6%)
Injury, poisoning and procedural complications
fall	2/50 (4%)
Musculoskeletal and connective tissue disorders
backache	2/50 (4%)
fracture	2/50 (4%)
Nervous system disorders
fibromyalgia flare	2/50 (4%)
Respiratory, thoracic and mediastinal disorders
upper respiratory infection	12/50 (24%)
sinusitis	3/50 (6%)
Skin and subcutaneous tissue disorders
rash	2/50 (4%)

Limitations/Caveats

An area of weakness to the study was the lack of direct comparison group.This was a single university study with two sites the cost,practicality of performing a noninferiority trial comparing these two pretreatment strategies was not feasible.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.