We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis (RATE-RA)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01382940
First Posted: June 27, 2011
Last Update Posted: August 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis Drug: rituximab Drug: methotrexate Drug: methylprednisolone Drug: acetaminophen Drug: antihistamine Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion [ Time Frame: Within 24 hours of beginning infusion on Day 15 ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Experiencing Any Serious IRR (SIRR) Associated With the Second Rituximab Infusion [ Time Frame: Within 24 hours of beginning infusion on Day 15 ]
    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.

  • Percentage of Participants Experiencing Any IRR or SIRR Associated With the Third Rituximab Infusion [ Time Frame: Within 24 hours of beginning infusion on Day 168 ]
    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.

  • Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Second Rituximab Infusion [ Time Frame: Within 24 hours of beginning infusion on Day 15 ]
    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.

  • Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Second Rituximab Infusion [ Time Frame: During the infusion (a 2-hour period) on Day 15 ]
    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.

  • Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Third Rituximab Infusion [ Time Frame: Within 24 hours of beginning infusion on Day 168 ]
    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".

  • Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Third Rituximab Infusion [ Time Frame: During the infusion (a 2-hour period) on Day 168 ]
    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.


Enrollment: 351
Actual Study Start Date: July 26, 2011
Study Completion Date: January 6, 2013
Primary Completion Date: January 6, 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Drug: rituximab
1000 mg in 250 mL intravenous infusion
Other Names:
  • Rituxan®
  • MabThera®
Drug: methotrexate
10 to 25 mg/week (oral or parenteral)
Drug: methylprednisolone
100 mg methylprednisolone administered by slow intravenous infusion at least 30 minutes prior to the start of each study drug infusion
Drug: acetaminophen
1 gram acetaminophen administered orally 30 to 60 minutes prior to the start of each study drug infusion
Drug: 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

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01382940


  Show 86 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01382940     History of Changes
Other Study ID Numbers: ML25641
First Submitted: June 24, 2011
First Posted: June 27, 2011
Results First Submitted: January 6, 2014
Results First Posted: February 19, 2014
Last Update Posted: August 1, 2017
Last Verified: July 2017

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Rituximab
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Methylprednisolone Hemisuccinate
Prednisolone
Acetaminophen
Methylprednisolone
Prednisolone acetate
Methylprednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Histamine Antagonists
Histamine H1 Antagonists
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action