Clinical trial NCT01532869: A Study of RoActemra/Actemra (Tocilizumab) Versus Placebo in Patients With Systemic Sclerosis
Official title: A Phase II/III, Multicenter, Randomized, Double-blind, Placebo-controlled Study To Assess The Efficacy And Safety Of Tocilizumab Versus Placebo In Patients With Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sclerosis, Systemic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-02-15
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Week 48
Secondary outcomes:
measure: Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI)
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 and Week 48
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in Clinician's Global Assessment at Week 24 and Week 48
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in Patient's Global Assessment at Week 24 and Week 48
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 and Week 48
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in 5-D Itch Scale at Week 24 and Week 48
timeFrame: Baseline, Weeks 24 and 48
measure: Change From Baseline in mRSS at Week 48
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Maintained or Improved in mRSS From Week 24 to Week 48
timeFrame: Week 48
measure: Change From Baseline in Tender Joint Count 28 (TJC28)
timeFrame: Baseline, Weeks 3, 8, 16, 24, 32, 40, and 48
measure: Area Under the Concentration-Time Curve (AUC) From Time 0 to 168 Hour (AUC0-168)
timeFrame: Pre-dose, 24, 48, 72, 96, 120 or 144, and 168 hours post dose for Baseline and Week 16
measure: Mean Serum Concentrations of Interleukin (IL)-6 by Visit
timeFrame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48
measure: Mean Serum Concentrations of Soluble IL-6 Receptor (R) by Visit
timeFrame: Baseline, Weeks 1, 2, 3, 8, 16, 24, and 48
measure: Percentage of Participants With Anti-Tocilizumab Antibody
timeFrame: Baseline, and post-baseline (up to Week 48)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: Stanford
country: United States
state: California
city: Farmington
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: New Brunswick
country: United States
state: New Jersey
city: Lake Success
country: United States
state: New York
city: New York
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Bordeaux
country: France
city: Caen
country: France
city: Lille
country: France
city: Paris
country: France
city: Strasbourg
country: France
city: Toulouse
country: France
city: Bad Nauheim
country: Germany
city: Baden-Baden
country: Germany
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Dresden
country: Germany
city: Erlangen
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Cannock
country: United Kingdom
city: Dundee
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Middlesborough
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Romford
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.