A Study of RoActemra/Actemra (Tocilizumab) Versus Placebo in Patients With Systemic Sclerosis

NCT01532869 | Completed Phase 3 Results DMC

• 2 other identifiers: WA277882011-001460-22
• Study Type: interventional
• Target: 87
• Locations: 5 countries
• Sites: 50

Brief Summary

This multicenter, randomized, double-blind, placebo-controlled, two-arm, parallel-group study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in participants with systemic sclerosis. Participants will be randomized to receive either RoActemra/Actemra 162 mg subcutaneously weekly or placebo for 48 weeks. From Week 48 to Week 96, all participants will receive open-label RoActemra/Actemra 162 mg subcutaneously weekly. Anticipated time on study treatment is 96 weeks.

Conditions

Sclerosis, Systemic

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24

  Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.

  Baseline, Week 24

• Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 8 after last dose that were absent before treatment or that worsened relative to pretreatment state.

  Week 48

Secondary Outcomes (13)

• Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI)

  Baseline, Weeks 24 and 48

• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48

  Baseline, Weeks 24 and 48

• Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48

  Baseline, Weeks 24 and 48

• Change From Baseline in Patient's Global Assessment at Week 24 and Week 48

  Baseline, Weeks 24 and 48

• Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48

  Baseline, Weeks 24 and 48

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: tocilizumab [RoActemra/Actemra]

Tocilizumab

EXPERIMENTAL

Drug: tocilizumab [RoActemra/Actemra]

Interventions

Placebo DRUG

Subcutaneously weekly, Weeks 0-48

Placebo

tocilizumab [RoActemra/Actemra] DRUG

162 mg subcutaneously weekly, Weeks 0-48

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, \>/= 18 years of age
• Systemic sclerosis, as defined by American College of Rheumatology (1980) criteria
• Disease duration of \</= 60 months (defined as time from first non-Raynaud phenomenon manifestation)
• \>/= 15 and \</= 40 mRSS units at screening
• Active disease, as defined by protocol
• Uninvolved skin at injection sites
• Negative pregnancy test for a female subject of childbearing potential

You may not qualify if:

• Major surgery (including joint surgery) within 8 weeks prior to and/or during study enrollment
• Rheumatic autoimmune disease other than systemic sclerosis
• Skin thickening (scleroderma) limited to areas distal to the elbows or knees at screening
• Previous treatment with tocilizumab
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Severe cardiopulmonary disease
• Known active current or history of recurrent infections
• Use of any investigational, biologic, or immunosuppressive therapies including intra-articular or parenteral corticosteroids prior to study enrollment as specified in the protocol
• As specified in the protocol, any current or past medical condition or medical history involving but not limited to the nervous, renal, pulmonary, endocrine, and gastrointestinal organ systems determined by the Principal Investigator to pose a significant safety risk to any subject while participating in the study
• Primary or secondary immunodeficiency

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (50)

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Los Angeles, California, 90025, United States

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San Diego, California, 44122, United States

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Stanford, California, 94305-5317, United States

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Farmington, Connecticut, 06030, United States

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Washington D.C., District of Columbia, 20007, United States

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Chicago, Illinois, 60611, United States

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Baltimore, Maryland, 21224, United States

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Boston, Massachusetts, 02118, United States

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Ann Arbor, Michigan, 48109-0934, United States

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New Brunswick, New Jersey, 08903, United States

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Lake Success, New York, 11042, United States

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New York, New York, 10021, United States

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Cleveland, Ohio, 44195, United States

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Toledo, Ohio, 43614, United States

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Oklahoma City, Oklahoma, 73103, United States

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Philadelphia, Pennsylvania, 19131, United States

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Pittsburgh, Pennsylvania, 15261, United States

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Charleston, South Carolina, 29425, United States

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Houston, Texas, 77030, United States

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Salt Lake City, Utah, 84132, United States

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Seattle, Washington, 98104, United States

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London, Ontario, N6A 4V2, Canada

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Toronto, Ontario, M5G 1X5, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Bordeaux, 33075, France

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Caen, 14033, France

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Lille, 59037, France

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Paris, 75679, France

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Strasbourg, 67091, France

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Toulouse, 31000, France

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Bad Nauheim, 61231, Germany

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Baden-Baden, 76530, Germany

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Berlin, 10177, Germany

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Bochum, 44791, Germany

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Cologne, 50937, Germany

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Dresden, 01067, Germany

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Erlangen, 91054, Germany

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Frankfurt, 60528, Germany

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Hamburg, 22763, Germany

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Tübingen, 72076, Germany

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Ulm, 89081, Germany

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Cannock, WS11 5XY, United Kingdom

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Dundee, DD1 9SY, United Kingdom

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Edinburgh, EH4 2XU, United Kingdom

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Leeds, LS7 4SA, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, NW3 2QG, 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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Romford, RM7 0AG, United Kingdom

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Related Publications (5)

• Gao X, Jia G, Guttman A, DePianto DJ, Morshead KB, Sun KH, Ramamoorthi N, Vander Heiden JA, Modrusan Z, Wolters PJ, Jahreis A, Arron JR, Khanna D, Ramalingam TR. Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis. Cell Rep Med. 2020 Nov 17;1(8):100140. doi: 10.1016/j.xcrm.2020.100140. eCollection 2020 Nov 17.

  PMID: 33294861 DERIVED

• Stifano G, Sornasse T, Rice LM, Na L, Chen-Harris H, Khanna D, Jahreis A, Zhang Y, Siegel J, Lafyatis R. Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol. 2018 Jun;70(6):912-919. doi: 10.1002/art.40455.

  PMID: 29858547 DERIVED

• Denton CP, Ong VH, Xu S, Chen-Harris H, Modrusan Z, Lafyatis R, Khanna D, Jahreis A, Siegel J, Sornasse T. Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis. Ann Rheum Dis. 2018 Sep;77(9):1362-1371. doi: 10.1136/annrheumdis-2018-213031. Epub 2018 May 31.

  PMID: 29853453 DERIVED

• Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Muller-Ladner U, Spotswood H, Burke L, Siegel J, Jahreis A, Furst DE. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018 Feb;77(2):212-220. doi: 10.1136/annrheumdis-2017-211682. Epub 2017 Oct 24.

  PMID: 29066464 DERIVED

• Khanna D, Denton CP, Jahreis A, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Muller-Ladner U, Lafyatis R, Stifano G, Spotswood H, Chen-Harris H, Dziadek S, Morimoto A, Sornasse T, Siegel J, Furst DE. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet. 2016 Jun 25;387(10038):2630-2640. doi: 10.1016/S0140-6736(16)00232-4. Epub 2016 May 5.

  PMID: 27156934 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 15, 2012
• Study Start: March 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: August 1, 2015
• Last Updated: September 23, 2016
• Results First Posted: November 5, 2015

Record last verified: 2016-08

Locations

DE (11); GB (9); CA (3); US (21); FR (6)