A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs)

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: tocilizumab [RoActemra/Actemra]; Drug: Nonbiologic DMARDs of investigator's choice

Study type: Interventional

Funder types: Industry

Identifiers

NCT00891020

ML22533

Details and patient eligibility

About

This 3 arm randomized open label study will evaluate the safety, tolerability and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to or are unable to tolerate DMARDs. The protocol incorporates risk mitigation strategies developed in partnership with the FDA to manage known and potential risks associated with the treatment of tocilizumab. Patients will be randomized to receive tocilizumab either 4 mg/kg intravenous (iv) or 8 mg/kg iv with concomitant non-biologic DMARDs, or 8 mg/kg iv without concomitant non-biologic DMARDs, every 4 weeks, for a total of 6 infusions. The anticipated time on study treatment is 3-12 months, and the target sample size is 500-1000 individuals.

Enrollment: 886 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• adult patients, >=18 years of age;
• moderate to severe active rheumatoid arthritis for >6 months;
• inadequate clinical response or unable to tolerate current or prior biologic or non-biologic Disease-modifying antirheumatic drug (DMARD) therapy;
• Swollen joint count (SJC) >/=4 and Tender joint count (TJC) >/=4
• body weight </=150kg
• current permitted non-biologic DMARDs must be on stable dose for >/= 7 weeks prior to baseline;

Exclusion criteria

• history of autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
• functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis;
• treatment with rituximab within 6 months before screening;
• intraarticular corticosteroids within 8 weeks or intramuscular (im)/ intravenous (iv) corticosteroids within 12 weeks prior to screening;
• known active current or history of recurrent infections, or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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886 participants in 3 patient groups

Tocilizumab 8 mg/kg Monotherapy

Experimental group

Description:

Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

Treatment:

Drug: tocilizumab [RoActemra/Actemra]

Drug: tocilizumab [RoActemra/Actemra]

Tocilizumab 4 mg/kg + DMARD

Experimental group

Description:

Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

Treatment:

Drug: Nonbiologic DMARDs of investigator's choice

Drug: tocilizumab [RoActemra/Actemra]

Drug: tocilizumab [RoActemra/Actemra]

Tocilizumab 8 mg/kg + DMARD

Experimental group

Description:

Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

Treatment:

Drug: Nonbiologic DMARDs of investigator's choice

Drug: tocilizumab [RoActemra/Actemra]

Drug: tocilizumab [RoActemra/Actemra]