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OpenTrials
Completed

NCT Number: NCT01194414

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

This randomized, double-blind, parallel group study compares the efficacy and safety of subcutaneous (sc) versus intravenous (iv) administration of tocilizumab in participants with moderate to severe active rheumatoid arthritis. Participants were randomized to receive either tocilizumab 162 mg sc weekly plus iv placebo every 4 weeks, or tocilizumab 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 was followed by a 72-week open-label treatment with some switching of sc and iv administration. No placebo was administered in the open-label phase. Participants continued on their stable dose of disease-modifying antirheumatic drugs (DMARDs) throughout the study. Anticipated time on study treatment was 2 years.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult participants, ≥ 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 tocilizumab
  • Active current or history of recurrent infection

Treatment and study plan

tocilizumab SC

Drug

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.

Other names: RoActemra/Actemra

tocilizumab IV

Drug

Tocilizumab supplied in vials as a sterile solution for 8 mg/kg intravenous infusion every 4 weeks.

Other names: RoActemra/Actemra

placebo to tocilizumab SC

Drug

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

Drug

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)

Drug

stable dose as prescribed

Primary outcomes

  1. Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR20) Response at Week 24

    Time frame: Baseline, 24 weeks

    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 [CRP] or Erythrocyte Sedimentation Rate [ESR]).

  2. Percentage of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Assessments

    Time frame: Baseline to up to 3 months after last dose of study drug (approximately up to 2 years)

Secondary outcomes

  1. Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR50) Response at Week 24

    Time frame: Baseline, 24 weeks

    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).

  2. Percentage of Participants Achieving an American College of Rheumatology Criteria (ACR70) Response at Week 24

    Time frame: Baseline, 24 weeks

    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).

  3. Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 24

    Time frame: 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.

  4. 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

    The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a participant 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.

  5. Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 24

    Time frame: 24 Weeks

    The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.

  6. Percentage of Participants With American College of Rheumatology Criteria (ACR20, ACR50, ACR70) at Week 97

    Time frame: Week 97

    ACR20, ACR50 and ACR70: ≥20%, ≥50% and ≥70% reduction from baseline for both TJC68 and SJC66, as well as for 3 of 5 additional ACR variables: Patient's Assessment of Pain in last 24 hours using a Visual Analog Scale (VAS) (0=no pain and 100=unbearable pain); Patient's and Physician's Global Assessment of Disease Activity in last 24 hours using a VAS (0=no disease activity and100=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 CRP or ESR). CRP was used for calculation of ACR. If missing, ESR was used. LOCF was used for missing joint counts, no imputation for other ACR components.

  7. Percentage of Participants With Disease Activity Score 28 (DAS28) Remission at Week 97

    Time frame: Week 97

    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. LOCF used for tender and swollen joint counts, no imputation used for ESR and Patient's Global Assessment of Disease Activity VAS.

  8. 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

    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. No imputation of missing scores was made other than for missing baseline scores, for which last score prior to baseline will be carried forward. For participants who prematurely withdrew, data collected at withdrawal visit was used and data thereafter is missing.

  9. Percentage of Participants Who Withdrew Because of Lack of Therapeutic Response at Week 97

    Time frame: Week 97

    The percentage of participants who withdrew from the study because they were not responding to treatment with the study drug.

  10. Area Under the Serum Concentration Curve of Tocilizumab After First SC Injection or IV Infusion

    Time frame: Week 0: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after first dose

  11. Area Under the Serum Concentration Curve of Tocilizumab at Steady State for SC and IV Treatment

    Time frame: Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose.

  12. Minimum Serum Concentration (Cmin) of Tocilizumab

    Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

  13. Maximum Serum Concentration (Cmax) of Tocilizumab

    Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

  14. Time to Maximum Serum Concentration (Tmax) of Tocilizumab

    Time frame: Week 0, Week 20: at 6 hours (hr), 24 hr, 48 hr, 96 hr, 120 hr and 168 hr after dose

  15. Change From Baseline in Serum Interleukin-6 (IL-6) Concentration at Week 25

    Time frame: Baseline, Week 25

  16. Change From Baseline in Serum Soluble Interleukin-6 Receptor (sIL-6R) Concentration at Week 97

    Time frame: Baseline, Week 97

  17. Percentage of Participants Who Developed Antibodies To Tocilizumab at Week 97

    Time frame: Week 97

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Randomized, Double-blind, Parallel Group 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

Important dates

Study start
2010
Primary completion
2012
Study completion
2013
First posted
Sep 3, 2010
Registry last updated
Jun 20, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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