A Study of RoActemra/Actemra (Tocilizumab) in Combination With Methotrexate in Patients With Severe Active Rheumatoid Arthritis, Comparing Tapering Versus Maintaining the Methotrexate Dosage

Rheumatoid Arthritis Clinical Trial

Official title:

Randomised, Phase IV, Placebo-controlled, Comparative Study to Evaluate the Efficacy and Safety of Tapering Methotrexate (MTX) Dosage Versus Maintaining the Dosage in Patients With Severe Active Rheumatoid Arthritis (RA) Who Have Demonstrated an Inadequate Response to Prior Conventional Disease-modifying Anti-rheumatic Drugs (DMARDs) Treatment and Have Initiated RoActemra® (Tocilizumab, TCZ) in Combination With MTX

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01661140
• Other study ID #: ML28096
• Secondary ID: 2011-005260-20
• Status: Terminated
• Phase: Phase 4
• First received: August 7, 2012
• Last updated: March 1, 2016
• Start date: November 2012
• Est. completion date: January 2015

Study information

• Verified date: March 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This randomized, placebo-controlled, double-blind study will compare the safety and efficacy of tapering methotrexate (MTX) versus maintaining MTX dosage in patients with severe active rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) initiated on treatment with RoActemra/Actemra. Patients will receive RoActemra/Actemra 8 mg/kg intravenously every 4 weeks and MTX orally weekly throughout the study. At Week 24, patients achieving a good/moderate EULAR response will be randomized to Group A receiving tapering doses of MTX or Group B maintaining their dose of MTX. Anticipated time on study treatment is 56 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 429
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Active severe rheumatoid arthritis (DAS28 > 5.1) according to EULAR/ACR criteria

• Inadequate response to a trial of 2 DMARDs, including methotrexate, a trial being defined as 6 months with 2 months at standard dose; no previous treatment with a TNF inhibitor

• Oral corticosteroids must have been at a stable dose of </= 10 mg/day prednisolone or equivalent for at least 25 out of 28 days prior to start of treatment (Day 1)

Exclusion Criteria:

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

• Rheumatic autoimmune disease other than rheumatoid arthritis

• Functional class IV as defined by the ACR Classification of Functional Status in RA

• Prior history of or current inflammatory joint disease other than RA

• Previous treatment with RoActemra/Actemra

• Previous treatment with any biologic drug (e.g. TNF inhibitor) that is used in the treatment of RA

• Intraarticular or parenteral corticosteroids within 6 weeks prior to enrollment

• Inadequate liver, bone marrow or hepatic function

• Positive for hepatitis B, hepatitis C or HIV infection

• Pregnant or breastfeeding women

• Females of child-bearing potential who are not using reliable means of contraception

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

• Active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections

• History of, or currently active, primary or secondary immunodeficiency

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• methotrexate
Stable or tapering oral weekly doses
• tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously every 4 weeks, 56 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients maintaining good/moderate European League Against Rheumatism (EULAR) response between Week 24 and Week 56		approximately 2.5 years	No
Secondary	Efficacy according to EULAR criteria		approximately 2.5 years	No
Secondary	Patient reported outcomes: Health Assessment Questionnaire (HAQ)/FACIT scale/SF 12		approximately 2.5 years	No
Secondary	Incidence of anaemia		approximately 2.5 years	No
Secondary	Change in work/productivity: Work Productivity and Activity Impairment Serious Health Problem (WPAI SHP) questionnaire		from baseline to Week 56	No
Secondary	Safety: Incidence of adverse events		approximately 2.5 years	No
Secondary	Proportion of patients able to discontinue methotrexate		approximately 2.5 years	No