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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194414
• Other study ID #: WA22762
• Secondary ID: 2010-018375-22
• Status: Completed
• Phase: Phase 3
• First received: September 1, 2010
• Last updated: September 6, 2013
• Start date: September 2010
• Est. completion date: June 2013

Study information

• Verified date: September 2013
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1262
• Est. completion date: June 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.
• 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.
• 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.
• 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.
• Disease-modifying antirheumatic drugs (DMARDs)
stable dose as prescribed

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Colombia,  France,  Germany,  Guatemala,  Hong Kong,  Italy,  Lithuania,  Mexico,  New Zealand,  Peru,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24	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).	Baseline, 24 weeks	No
Primary	Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments		through to study end (up to 4 years)	Yes
Secondary	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24	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).	Baseline, 24 weeks	No
Secondary	Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24	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).	Baseline, 24 weeks	No
Secondary	Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24	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.	Week 24	No
Secondary	Percentage of Participants Achieving a Decrease of = 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24	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.	Baseline, 24 Weeks	No
Secondary	Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24	The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.	24 Weeks	No
Secondary	Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70)		97 weeks	No
Secondary	Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97		97 weeks	No
Secondary	Percentage of Participants Achieving a Decrease of = 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 97		Baseline, Week 97	No
Secondary	Pharmacokinetics (AUC, Cmin, Cmax, Tmax) and Pharmacodynamics (Interleukin-6, Soluble Interleukin-6 Receptor) of Tocilizumab After sc Administration		97 weeks	No
Secondary	Immunogenicity of Tocilizumab (TCZ) Following sc Administration: Anti-TCZ Antibodies		97 weeks	No
Secondary	Effect of Switch From iv to sc Administration (Efficacy, Safety, PK, PD)		from week 25 to week 97	No