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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01194414
First received: September 1, 2010
Last updated: September 6, 2013
Last verified: September 2013
  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:


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
Study Completion Date: June 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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: September 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Antirheumatic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014