NCT01194414

Brief Summary

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
1,262

participants targeted

Target at P75+ for phase_3 rheumatoid-arthritis

Timeline
Completed

Started Sep 2010

Typical duration for phase_3 rheumatoid-arthritis

Geographic Reach
26 countries

216 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 1, 2010

Completed
Same day until next milestone

Study Start

First participant enrolled

September 1, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 3, 2010

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

February 12, 2013

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2013

Completed
Last Updated

June 20, 2016

Status Verified

September 1, 2013

Enrollment Period

1.3 years

First QC Date

September 1, 2010

Results QC Date

January 7, 2013

Last Update Submit

May 11, 2016

Conditions

Outcome Measures

Primary Outcomes (2)

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

    Baseline, 24 weeks

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

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

Secondary Outcomes (17)

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

    Baseline, 24 weeks

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

    Baseline, 24 weeks

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

    Week 24

  • Percentage of Participants Achieving a Decrease of ≥ 0.3 in the Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline to Week 24

    Baseline, 24 Weeks

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

    24 Weeks

  • +12 more secondary outcomes

Study Arms (4)

Tocilizumab SC

EXPERIMENTAL

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. Participants continued to receive tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Drug: tocilizumab SCDrug: placebo to tocilizumab IVDrug: Disease-modifying antirheumatic drugs (DMARDs)

Tocilizumab IV

EXPERIMENTAL

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. Participants continued to receive tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Drug: tocilizumab IVDrug: placebo to tocilizumab SCDrug: Disease-modifying antirheumatic drugs (DMARDs)

Tocilizumab SC Then Tocilizumab IV

EXPERIMENTAL

Participants who received tocilizumab 162 mg subcutaneous (SC) injection weekly plus placebo to tocilizumab IV infusion every 4 weeks for 24 weeks in double blind treatment period switched to tocilizumab 8 mg/kg IV infusion every 4 weeks for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose continued throughout the study.

Drug: tocilizumab SCDrug: tocilizumab IVDrug: placebo to tocilizumab IVDrug: Disease-modifying antirheumatic drugs (DMARDs)

Tocilizumab IV Then Tocilizumab SC

EXPERIMENTAL

Participants who received tocilizumab 8 mg/kg infusion (IV) every 4 weeks plus placebo to tocilizumab SC injection weekly in double blind treatment period switched to tocilizumab 162 mg SC injection weekly for a total of 72 weeks in open label extension period. Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) at a stable dose will be continued throughout the study.

Drug: tocilizumab SCDrug: tocilizumab IVDrug: placebo to tocilizumab SCDrug: Disease-modifying antirheumatic drugs (DMARDs)

Interventions

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.

Also known as: RoActemra/Actemra
Tocilizumab IV Then Tocilizumab SCTocilizumab SCTocilizumab SC Then Tocilizumab IV

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

Also known as: RoActemra/Actemra
Tocilizumab IVTocilizumab IV Then Tocilizumab SCTocilizumab SC Then Tocilizumab IV

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.

Tocilizumab IVTocilizumab IV Then Tocilizumab SC

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.

Tocilizumab SCTocilizumab SC Then Tocilizumab IV

stable dose as prescribed

Tocilizumab IVTocilizumab IV Then Tocilizumab SCTocilizumab SCTocilizumab SC Then Tocilizumab IV

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (216)

Unknown Facility

Huntsville, Alabama, 35801, United States

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Tuscaloosa, Alabama, 35406, United States

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Tucson, Arizona, 85704, United States

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Tucson, Arizona, 85712, United States

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Long Beach, California, 90806, United States

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Los Angeles, California, 90048, United States

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Upland, California, 91786, United States

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Van Nuys, California, 91405, United States

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Denver, Colorado, 80230-7127, United States

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Bridgeport, Connecticut, 06606, United States

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Delray Beach, Florida, 33484, United States

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Miami, Florida, 33133, United States

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Ocala, Florida, 34474, United States

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Orlando, Florida, 32806, United States

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Palm Harbor, Florida, 34684, United States

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Pinellas Park, Florida, 33782, United States

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South Miami, Florida, 33143, United States

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Tampa, Florida, 33614, United States

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Coeur d'Alene, Idaho, 83814, United States

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Morton Grove, Illinois, 60053, United States

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Wichita, Kansas, 67208, United States

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Monroe, Louisiana, 71203, United States

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Petoskey, Michigan, 49770, United States

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Saint Claire Shores, Michigan, 48081, United States

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Eagan, Minnesota, 55121, United States

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Florissant, Missouri, 63031, United States

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St Louis, Missouri, 63117, United States

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St Louis, Missouri, 63131, United States

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Lebanon, New Hampshire, 03756, United States

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Clifton, New Jersey, 07012, United States

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Manalapan, New Jersey, 07726, United States

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Voorhees Township, New Jersey, 08043, United States

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Albuquerque, New Mexico, 87102, United States

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Albany, New York, 12206, United States

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Binghamton, New York, 13905, United States

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Orchard Park, New York, 14127, United States

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Asheville, North Carolina, 28803, United States

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Raleigh, North Carolina, 27609, United States

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Wilmington, North Carolina, 28401, United States

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Cincinnati, Ohio, 45219, United States

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Toledo, Ohio, 43623, United States

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Oklahoma City, Oklahoma, 73103, United States

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Tulsa, Oklahoma, 74135, United States

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Bethlehem, Pennsylvania, 18015, United States

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Charleston, South Carolina, 29406, United States

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Charleston, South Carolina, 29407, United States

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Knoxville, Tennessee, 37909, United States

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Memphis, Tennessee, 38119, United States

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Houston, Texas, 77004, United States

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San Antonio, Texas, 78217, United States

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Olympia, Washington, 98502, United States

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Seattle, Washington, 98122, United States

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Spokane, Washington, 99204, United States

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Wenatchee, Washington, 98801, United States

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Buenos Aires, B1878DVB, Argentina

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Buenos Aires, C1015ABO, Argentina

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Buenos Aires, C1428DQG, Argentina

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Rosario, S2000PBJ, Argentina

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Adelaide, 5011, Australia

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Adelaide, 5041, Australia

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Clayton, 3168, Australia

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Geelong, 3220, Australia

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Hobart, 7000, Australia

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Malvern East, 3145, Australia

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Maroochydore, 4558, Australia

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New Lambton, 2305, Australia

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Curitiba, 80060-240, Brazil

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Goiânia, 74110010, Brazil

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Juiz de Fora, 36010-570, Brazil

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Porto Alegre, 90035-903, Brazil

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Porto Alegre, 90610-000, Brazil

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São Paulo, 04039-000, Brazil

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São Paulo, 05403-000, Brazil

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São Paulo, 4037003, Brazil

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Sofia, 1606, Bulgaria

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Sofia, 1612, Bulgaria

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Sofia, 1784, Bulgaria

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Edmonton, Alberta, T5H 3V9, Canada

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Kelowna, British Columbia, V1Y 3G8, Canada

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Vancouver, British Columbia, V5Z 1L7, Canada

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St. John's, Newfoundland and Labrador, A1A 5E8, Canada

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St. John's, Newfoundland and Labrador, A1C 5B8, Canada

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Hamilton, Ontario, L8N 1Y2, Canada

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Hamilton, Ontario, L8N 2B6, Canada

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Kitchener, Ontario, N2M 5N6, Canada

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Ottawa, Ontario, K1Y 4G2, Canada

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St. Catharines, Ontario, L2N 7E4, Canada

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Windsor, Ontario, N8X 5A6, Canada

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Montreal, Quebec, H2L 1S6, Canada

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Québec, Quebec, G1V 3M7, Canada

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Rimouski, Quebec, G5L 3W1, Canada

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Sainte-Foy, Quebec, G1W 4R4, Canada

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Trois-Rivières, Quebec, G8Z 1Y2, Canada

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Saskatoon, Saskatchewan, S7K 0H6, Canada

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Barranquilla, Colombia

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Bogotá, Colombia

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Bordeaux, 33076, France

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Le Mans, 72037, France

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Marseille, 13285, France

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Montpellier, 34295, France

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Nantes, 44035, France

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Paris, 75679, France

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Strasbourg, 67098, France

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Toulouse, 31059, France

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Bad Bramstedt, 24576, Germany

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Berlin, 10117, Germany

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Berlin, 14059, Germany

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Cologne, 50924, Germany

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Dresden, 01067, Germany

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Essen, 45239, Germany

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Freiburg im Breisgau, 79106, Germany

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Gommern, 39245, Germany

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Heidelberg, 69120, Germany

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Herne, 44652, Germany

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Hildesheim, 31134, Germany

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Ludwigshafen, 67063, Germany

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Osnabrück, 49074, Germany

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Ratingen, 40882, Germany

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Rostock, 18059, Germany

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Würzburg, 97080, Germany

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Guatemala City, 01010, Guatemala

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Guatemala City, 01015, Guatemala

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Hong Kong, 852, Hong Kong

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Hong Kong, Hong Kong

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Arenzano, 16011, Italy

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Bergamo, 24128, Italy

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Catania, 95124, Italy

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Cona (ferrara), 44124, Italy

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Genova, 16132, Italy

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Napoli, 80131, Italy

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Pavia, 27100, Italy

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Pisa, 56100, Italy

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Potenza, 85100, Italy

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Reggio Emilia, 42100, Italy

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Udine, 33100, Italy

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Varese, 21100, Italy

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Klaipėda, 92288, Lithuania

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Šiauliai, 76231, Lithuania

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Vilnius, LT-08661, Lithuania

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Culiacán, 80000, Mexico

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Guadalajara, 44629, Mexico

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Guadalajara, 44690, Mexico

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León, 37000, Mexico

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Mexico Ctiy, 07760, Mexico

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Mérida, 97000, Mexico

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Miexico City, 06700, Mexico

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Morelia, 58070, Mexico

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Obregón, 85000, Mexico

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Querétaro, 76178, Mexico

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Saltillo, 25000, Mexico

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Torreón, 27000, Mexico

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Auckland, 2025, New Zealand

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Hamilton, 3240, New Zealand

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Tauranga, 3112, New Zealand

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Wellington, 6035, New Zealand

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Lima, 01, Peru

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Lima, LIMA 14, Peru

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Lima, Lima 41, Peru

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Cebu, 6000, Philippines

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Manila, 1000, Philippines

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Quezon, 1102, Philippines

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Bialystok, 15-351, Poland

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Lublin, 20-954, Poland

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Poznan, 60-218, Poland

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Warsaw, 01-157, Poland

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Ponce, 00716, Puerto Rico

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Bucharest, 011172, Romania

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Bucharest, 020475, Romania

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Bucharest, 020983, Romania

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Iași, 700661, Romania

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Moscow, 115522, Russia

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Moscow, 119991, Russia

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Novosibirsk, 630099, Russia

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Novosibirsk, 630117, Russia

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Ryazan, 390026, Russia

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Saint Petersburg, 190068, Russia

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Ulyanovsk, 432600, Russia

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Yaroslavl, 150030, Russia

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Yaroslavl, 150062, Russia

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Singapore, 119074, Singapore

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Cape Town, 7500, South Africa

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Durban, 4001, South Africa

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Parktown, 2000, South Africa

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Port Elizabeth, 6045, South Africa

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Stellenbosch, 7600, South Africa

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A Coruña, 15006, Spain

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Barakaldo, 48903, Spain

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Bilbao, 48013, Spain

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Madrid, 28007, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Mérida, 97500, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Santander, 39008, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41009, Spain

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Torrelavega, 39300, Spain

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Valencia, 46009, Spain

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Khon Kaen, 40002, Thailand

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Cambridge, CB2 2QQ, United Kingdom

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Cannock, WS11 5XY, United Kingdom

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Coventry, CV2 2DX, United Kingdom

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Eastbourne, BN21 2UD, United Kingdom

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Exeter, EX2 5DW, United Kingdom

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Harrogate, HG2 7SX, United Kingdom

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Ipswich, IP4 5PD, United Kingdom

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London, E11 1NR, United Kingdom

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Metropolitan Borough of Wirral, CH49 5PE, United Kingdom

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Middlesbrough, TS4 3BW, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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Northampton, NN1 5BD, United Kingdom

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Nottingham, NG7 2UH, United Kingdom

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Westcliffe-on-sea, SS0 0RY, United Kingdom

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Related Publications (1)

  • Burmester GR, Rubbert-Roth A, Cantagrel A, Hall S, Leszczynski P, Feldman D, Rangaraj MJ, Roane G, Ludivico C, Bao M, Rowell L, Davies C, Mysler EF. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis. 2016 Jan;75(1):68-74. doi: 10.1136/annrheumdis-2015-207281. Epub 2015 Jun 8.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumabAntirheumatic Agents

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutic UsesPharmacologic ActionsChemical Actions and Uses

Results Point of Contact

Title
Medical Communications
Organization
Hoffman-LaRoche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 1, 2010

First Posted

September 3, 2010

Study Start

September 1, 2010

Primary Completion

January 1, 2012

Study Completion

August 1, 2013

Last Updated

June 20, 2016

Results First Posted

February 12, 2013

Record last verified: 2013-09

Locations