A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis (RATE-RA)
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| ClinicalTrials.gov Identifier: NCT01382940 |
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Recruitment Status :
Completed
First Posted : June 27, 2011
Results First Posted : February 19, 2014
Last Update Posted : August 1, 2017
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rheumatoid Arthritis | Drug: rituximab Drug: methotrexate Drug: methylprednisolone Drug: acetaminophen Drug: antihistamine | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 351 participants |
| Allocation: | N/A |
| 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 |
| Actual Study Start Date : | July 26, 2011 |
| Actual Primary Completion Date : | January 6, 2013 |
| Actual Study Completion Date : | January 6, 2013 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Rheumatoid arthritis
Drug Information available for:
Rituximab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: rituximab
1000 mg in 250 mL intravenous infusion
Other Names:
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 |
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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
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
Locations
Show 86 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT01382940 |
| Other Study ID Numbers: |
ML25641 |
| First Posted: | June 27, 2011 Key Record Dates |
| Results First Posted: | February 19, 2014 |
| Last Update Posted: | August 1, 2017 |
| Last Verified: | July 2017 |
Additional relevant MeSH terms:
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Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Acetaminophen Methylprednisolone Rituximab Methotrexate Histamine Antagonists Histamine H1 Antagonists Antineoplastic Agents, Immunological |
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 Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Nucleic Acid Synthesis Inhibitors |