A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— RATE-RA  

Official title:

A Multicenter, Open-label, Single-arm Study to Evaluate the Safety Administering Rituximab at a More Rapid Infusion Rate in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01382940
• Other study ID #: ML25641
• Status: Completed
• Phase: Phase 4
• First received: June 24, 2011
• Last updated: March 3, 2014
• Start date: July 2011
• Est. completion date: February 2013

Study information

• Verified date: January 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study was designed to evaluate the safety of administering rituximab at a more rapid infusion rate in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to biopharmaceuticals that treat diseases by interfering with tumor necrosis factor (anti-TNF therapies), and were receiving methotrexate therapy for more than eight weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 351
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Adult patients, = 18 years of age

• Rheumatoid arthritis of = 6 months duration, diagnosed according to the revised 1987 American College of Rheumatology criteria

• Inadequate response to at least one approved anti-TNF agent (adalimumab, etanercept, infliximab, golimumab, or certolizumab)

• Patients who have received 1 to 2 prior courses of rituximab (RTX) may be enrolled, provided their most recent course of RTX occurred over 6 months but no more than 9 months prior to baseline. The RTX dosage must have been two 1000 mg infusions per course administered at the standard approved rate

• Methotrexate treatment between 10 and 25 mg/week (oral or parenteral) for at least 8 weeks immediately prior to baseline

Key Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following baseline

• Rheumatic autoimmune disease other than rheumatoid arthritis

• Functional class IV as defined by American College of Rheumatology (ACR) criteria

• Prior history of or current inflammatory joint disease other than rheumatoid arthritis

• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies

• Previous serious infusion reaction to any prior biologic therapy

• Known active current or history of recurrent infection

• Evidence of chronic hepatitis B or C infection

• Pregnant or lactating women

• Body weight of > 150 kg

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• rituximab
1000 mg in 250 mL intravenous infusion
• methotrexate
10 to 25 mg/week (oral or parenteral)
• methylprednisolone
100 mg methylprednisolone administered by slow intravenous infusion at least 30 minutes prior to the start of each study drug infusion
• acetaminophen
1 gram acetaminophen administered orally 30 to 60 minutes prior to the start of each study drug infusion
• antihistamine
50 mg diphenhydramine hydrochloride or equivalent dose of alternate antihistamine administered orally 30 to 60 minutes prior to the start of each study drug infusion

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion	The primary criterion for assessing safety of the faster infusion was the incidence of infusion related reaction (IRRs). IRRs were adverse events (AEs) that occurred within 24 hours of beginning infusion that were among a pre-specified list of preferred terms from the Medical Dictionary for Regulatory Activities (MedDRA). "Incidence" is defined as the percentage of participants experiencing an IRR.	Within 24 hours of beginning infusion on Day 15	Yes
Secondary	Percentage of Participants Experiencing Any Serious IRR (SIRR) Associated With the Second Rituximab Infusion	A serious infusion-related reaction (SIRR) is an IRR that meets the definition of a serious adverse event. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution.	Within 24 hours of beginning infusion on Day 15	Yes
Secondary	Percentage of Participants Experiencing Any IRR or SIRR Associated With the Third Rituximab Infusion	IRRs are AEs that occurred within 24 hours of beginning infusion that were included on a pre-specified list of MedDRA preferred terms, and an SIRR is an IRR that suggests a significant hazard, contraindication, side effect or precaution.	Within 24 hours of beginning infusion on Day 168	Yes
Secondary	Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Second Rituximab Infusion	The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0), where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: Grade 3 means "Severe", indicating considerable interference with the patient's daily activities; medical intervention/therapy required; and hospitalization possible.; Grade 4 means "Life-threatening, Disabling", based on extreme limitation in activity; significant medical intervention/therapy required, and hospitalization probable.	Within 24 hours of beginning infusion on Day 15	Yes
Secondary	Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Second Rituximab Infusion	Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment.; The CTCAE includes the following severity descriptions: "Moderate" means mild to moderate interference with the patient's daily activities, no or minimal medical intervention/therapy required; "Severe" means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible.; If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.	During the infusion (a 2-hour period) on Day 15	Yes
Secondary	Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Third Rituximab Infusion	The intensity of AEs experienced within 24 hours of beginning infusion were graded on NCI's CTCAE (v. 4.0) intensity scale from Grade 1 ("Mild") to Grade 5 ("Death"). Grade 3 AEs are "Severe" and Grade 4 AEs are "Life-threatening, Disabling".	Within 24 hours of beginning infusion on Day 168	Yes
Secondary	Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Third Rituximab Infusion	Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment.; The CTCAE includes the following severity descriptions: "Moderate" means mild to moderate interference with the patient's daily activities, no or minimal medical intervention/therapy required; "Severe" means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible.; If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.	During the infusion (a 2-hour period) on Day 168	Yes