A Study to Compare Subcutaneous Versus Intravenous Administration of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Active Rheumatoid Arthritis - Full Text View

Purpose

This randomized, double-blind, parallel group study will compare the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of RoActemra/Actemra (tocilizumab) in patients with moderate to severe active rheumatoid arthritis. Patients will be randomized to receive either RoActemra/Actemra 162 mg sc weekly plus iv placebo every 4 weeks, or RoActemra/Actemra 8 mg/kg iv every 4 weeks plus sc placebo weekly during the double-blind period from baseline to Week 24. The double-blind period will be followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo will be administered in the open-label phase. Patients will continue on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment is 2 years.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: tocilizumab SC Drug: tocilizumab IV Drug: placebo to tocilizumab SC Drug: placebo to tocilizumab IV Drug: Disease-modifying antirheumatic drugs (DMARDs)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-blind, Parallel Group Study Study of the Safety and Effect on Clinical Outcome of Tocilizumab SC Versus Tocilizumab IV, in Combination With Traditional Disease Modifying Anti-rheumatic Drugs (DMARDs), in Patients With Moderate to Severe Active Rheumatoid Arthritis

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Tocilizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments [ Time Frame: through to study end (up to 4 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24 [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: No ]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the five additional ACR core set variables: Patient's Assessment of Pain over the previous 24 hours using a Visual Analog Scale (VAS) where left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions in 8 areas (dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities) answered on a scale of 0=without difficulty to 3=unable to do; and acute-phase reactant (either C-reactive protein or Erythrocyte Sedimentation Rate).
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
The DAS28 (ESR) score is a measure of the subject's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity VAS where left side of the line 0=no disease activity to right side of the line 100=extreme disease activity and ESR. DAS28-(ESR) total scores range from 0 - 10. Remission is defined as achieving a DAS28-ESR score of less than 2.6.
Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24 [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0(without any difficulty) to 4 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. A decrease indicates improvement.
Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.
Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97 [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97 [ Time Frame: Baseline, Week 97 ] [ Designated as safety issue: No ]
Pharmacokinetics (AUC, Cmin, Cmax, Tmax) and Pharmacodynamics (Interleukin-6, Soluble Interleukin-6 Receptor) of Tocilizumab After sc Administration [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Immunogenicity of Tocilizumab (TCZ) Following sc Administration: Anti-TCZ Antibodies [ Time Frame: 97 weeks ] [ Designated as safety issue: No ]
Effect of Switch From iv to sc Administration (Efficacy, Safety, PK, PD) [ Time Frame: from week 25 to week 97 ] [ Designated as safety issue: No ]

Enrollment:	1262
Study Start Date:	September 2010
Estimated Study Completion Date:	December 2013
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: tocilizumab SC Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Drug: tocilizumab SC Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week for a total of 24 weeks in the double-blind period. Other Name: RoActemra/Actemra Drug: placebo to tocilizumab IV Placebo to tocilizumab supplied as a solution in 10 mL vials containing polysorbate 80 and sucrose in water for infusion every 4 weeks for a total of 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed
Active Comparator: tocilizumab IV Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.	Drug: tocilizumab IV Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks for a total of 24 weeks in the double-blind period. Other Name: RoActemra/Actemra Drug: placebo to tocilizumab SC Placebo tocilizumab supplied as a single-use pre-filled syringe with a needle safety device, delivering 0.9 mL sodium chloride for subcutaneous injection once a week for 24 weeks in the double-blind period. Drug: Disease-modifying antirheumatic drugs (DMARDs) stable dose as prescribed

Arms

Assigned Interventions

Experimental: tocilizumab SC

Participants received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab intravenous (IV) infusion every 4 weeks for a total of 24 weeks in the double-blind period.

Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.

Drug: tocilizumab SC

Tocilizumab supplied in a single-use pre-filled syringe, with a needle safety device, delivering 162 mg/0.9 mL solution for subcutaneous injection once a week for a total of 24 weeks in the double-blind period.

Other Name: RoActemra/Actemra

Drug: placebo to tocilizumab IV

Placebo to tocilizumab supplied as a solution in 10 mL vials containing polysorbate 80 and sucrose in water for infusion every 4 weeks for a total of 24 weeks in the double-blind period.

Drug: Disease-modifying antirheumatic drugs (DMARDs)

stable dose as prescribed

Active Comparator: tocilizumab IV

Participants received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly for a total of 24 weeks in the double-blind period.

Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose beginning at least 8 weeks prior to baseline were a requirement of the study.

Drug: tocilizumab IV

Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks for a total of 24 weeks in the double-blind period.

Other Name: RoActemra/Actemra

Drug: placebo to tocilizumab SC

Placebo tocilizumab supplied as a single-use pre-filled syringe with a needle safety device, delivering 0.9 mL sodium chloride for subcutaneous injection once a week for 24 weeks in the double-blind period.

Drug: Disease-modifying antirheumatic drugs (DMARDs)

stable dose as prescribed

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult patients, ≥ 18 years of age
Rheumatoid arthritis of ≥ 6 months duration, according to American College of Rheumatology (ACR) criteria
Swollen joint count (SJC) ≥ 4 (66 joint count), tender joint count (TJC) ≥ 4 (68 joint count) at screening and baseline
Inadequate response to current DMARD therapy
Permitted DMARDs must be at stable dose for ≥ 8 weeks prior to baseline
Oral corticosteroids (≤ 10 mg/day prednisone or equivalent) and NSAIDs (up to maximum recommended dose) must be at stable dose for ≥ 4 weeks prior to baseline

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 RA
Functional class IV (ACR classification)
Diagnosis of juvenile idiopathic arthritis (JIA) or juvenile rheumatoid arthritis (JRA) and/or RA before the age of 16
Prior history of or current inflammatory joint disease other than RA
Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
Previous treatment with RoActemra/Actemra
Active current or history of recurrent infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194414

Show 217 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01194414 History of Changes
Other Study ID Numbers:	WA22762, 2010-018375-22
Study First Received:	September 1, 2010
Results First Received:	January 7, 2013
Last Updated:	March 22, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases

Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013