A Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis (SSc)

Systemic Sclerosis Clinical Trial

— focuSSced  

Official title:

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy and Safety of Tocilizumab Versus Placebo in Patients With Systemic Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02453256
• Other study ID #: WA29767
• Secondary ID: 2015-000424-28
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2015
• Est. completion date: February 4, 2019

Study information

• Verified date: March 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of tocilizumab compared with placebo in participants with SSc across approximately 120 planned global study sites. The study will consist of a 48-week, double-blind, placebo-controlled period followed by a 48-week open-label treatment period. Participants will be assigned, in a 1:1 ratio, to double-blind treatment with active tocilizumab or matching placebo. In the open-label period, eligible participants from either arm may receive active tocilizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: February 4, 2019
• Est. primary completion date: January 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of SSc according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria, meeting criteria for active disease and with total disease duration of less than or equal to (</=) 60 months

• mRSS of 10-35 units, inclusive

• Agreement to remain abstinent or use an effective contraceptive method among males and females with childbearing potential

Exclusion Criteria:

• Pregnant or lactating females

• Major surgery within 8 weeks prior to screening

• Scleroderma limited to the face or areas distal to the elbows or knees

• Rheumatic autoimmune disease other than SSc

• Immunization with a live or attenuated vaccine within 4 weeks prior to Baseline

• Known hypersensitivity to human, humanized, or murine monoclonal antibodies

• Moderately severe nervous system, renal, endocrine, pulmonary, cardiovascular, or gastrointestinal (GI) disease not related to SSc, including diverticulitis or ulcerative lower GI disorders, or myocardial infarction (MI) within 6 months prior to screening

• Active or significant history of infection, including treatment with intravenous (IV) antibiotics within 4 weeks or oral antibiotics within 2 weeks prior to screening

• Significant history of tuberculosis (TB)

• Primary or secondary immunodeficiency

• Malignant disease, with the exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix

• History of drug or alcohol abuse

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Placebo
Participants will receive matching placebo subcutaneous (SC) injections once weekly for 48 weeks of double-blind treatment.
• Tocilizumab
Participants will receive 162 mg SC tocilizumab once weekly for 48 weeks of double-blind treatment. The same regimen will be given to all eligible participants for 48 weeks of open-label treatment.

Locations

Country	Name	City	State
Argentina	Hospital Britanico; Haematology	Buenos Aires
Argentina	Organizacion Medica de Investigacion	Buenos Aires
Argentina	Sanatorio Parque S.A.	Rosario, Santa FE
Argentina	Centro de Investigaciones Reumatologicas Tucuman	Tucuman
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Bulgaria	MHAT Kaspela; Rheumatology	Plovdiv
Bulgaria	MHAT-Plovdiv AD; Reumatology Department	Plovdiv
Bulgaria	MHAT St.Ivan Rilski; Rheumtology Department	Sofia
Bulgaria	MHAT Sv.Ivan Rilski; Clinic of Rheumatology	Sofia
Canada	Mount Sinai Hospital; Rebecca Macdonald Centre For Arthritis & Autoimmune Disease	Toronto	Ontario
Canada	St. Paul's Hospital University of British Colambia Division of Hematology	Vancouver	British Columbia
Denmark	Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme	Aarhus N
Denmark	Bispebjerg Hospital, Dermatologisk afdeling	København NV
France	Hopital Claude Huriez; Internal Medicine	Lille
Germany	Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie	Bad Abbach
Germany	Kerckhoff-Klinik; Rheumatologie&klin.Immunologie	Bad Nauheim
Germany	Universitätsklinikum Dresden; Technische Universität Dresden; Rheumatologie, Innere Medizin III	Dresden
Germany	Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV	München
Germany	Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II	Tübingen
Greece	Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens	Athens
Greece	University Hospital of Patras; Rheumatology	Patras
Hungary	National Institute of Rheumatology and Physiology	Budapest
Hungary	Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika	Pécs
Italy	Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia	Firenze	Toscana
Italy	Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica	Milano	Lombardia
Italy	Policlinico Universitario-II Università di Napoli; Reumatologia	Napoli	Campania
Italy	Uni ' Cattolica Del Sacro Cuore; Facoltà Di Medicina E Chirurgia A.Gemelli-Clinica Reumatologica	Roma	Lazio
Japan	Gunma University Hospital	Gunma
Japan	Hokkaido University Hospital	Hokkaido
Japan	Sapporo Medical University Hospital	Hokkaido
Japan	Kanazawa University Hospital	Ishikawa
Japan	St. Marianna University School of Medicine Hospital	Kanagawa
Japan	Hospital of the University of Occupational and Environmental Health,Japan	Kitakyushu-shi
Japan	Kumamoto University Hospital	Kumamoto
Japan	Tohoku University Hospital	Miyagi
Japan	Osaka University Hospital	Osaka
Japan	Nippon Medical School Hospital	Tokyo
Japan	The University of Tokyo Hospital	Tokyo
Lithuania	Klaipeda University Hospital; Department of Rheumatology	Klaipeda
Lithuania	Vilnius University Hospital Santariskiu Clinic Public Insti	Vilnius
Mexico	Unidad De Enfermedades; Cronico Degenerativas, SC.	Mexico
Mexico	Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán	Mexico City
Mexico	Cliditer SA de CV	Miexico City
Netherlands	Academisch Ziekenhuis Leiden; Dept of Rheumatology	Leiden
Poland	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Wewnetrznych, Chorob Tkanki Lacznej i Geriatrii	Gdansk
Poland	Gornoslaskie Centrum Medyczne	Katowice
Poland	Szpital Specjalistyczny im Jozefa Dietla; Centrum Reumatologii, Immunologii i Rehabilitacji, I Oddzi	Krakow
Poland	SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki	Lublin
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher	Warszawa
Portugal	Hospital Garcia de Orta; Servico de Reumatologia	Almada
Portugal	Hospital Prof. Dr. Fernando Fonseca; Medicina IV	Amadora
Puerto Rico	Puerto Rico Clinical & Translational Research Consortium	San Juan
Romania	Cantacuzino Hospital; Department of Internal Medicine and Rheumatology	Bucharest
Romania	Spitalul Judetean Cluj; Sectia de Reumatologie	Cluj-napoca
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Medicina Interna/Reumatologia	Barcelona
Spain	Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Reumatología	Madrid
Switzerland	Universitätsspital Basel; Rheumatologische Poliklinik	Basel
Switzerland	Universitätsspital Zürich; Klinik für Rheumatologie	Zürich
United Kingdom	Queen Elizabeth Hospital; Rheumatology Dept.	Birmingham
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine	Leeds
United Kingdom	Uni Hospital Aintree; Academic Rheumatology Unit	Liverpool
United Kingdom	Royal Free Hospital; Department of Rheumatology	London
United Kingdom	Freeman Hospital; Musculoskeletal Unit	Newcastle Upon Tyne
United States	University of Michigan	Ann Arbor	Michigan
United States	Rheumatology Assoc. of S. Florida - Clinical Research Center	Boca Raton	Florida
United States	Boston Univ Med Center - AC	Boston	Massachusetts
United States	Joint & Muscle Research Institute	Charlotte	North Carolina
United States	Metroplex Clinical Research	Dallas	Texas
United States	TriWest Research Associates, LLC	El Cajon	California
United States	St. Joseph's Heritage Healthcare	Fullerton	California
United States	West Michigan Rheumatology, PLLC	Grand Rapids	Michigan
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Arthritis Associates of Southern California	Los Angeles	California
United States	Univ of Calif., Los Angeles; Rheumatology	Los Angeles	California
United States	Arthritis and Rheumatology; Center of Oklahoma PLLC	Oklahoma City	Oklahoma
United States	Millenium Research	Ormond Beach	Florida
United States	Thomas Jefferson Uni ; Division of Rheumatology	Philadelphia	Pennsylvania
United States	Georgetown Uni. Hosp.; Rheumatology, Immunology and Allergy Dept.	Washington	District of Columbia
United States	Clinical Research Center of Reading	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Lithuania,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  Romania,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period	The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units.	From baseline to week 48
Secondary	Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period	The proportion of participants with threshold improvements in mRSS at Week 48 relative to baseline.	From Baseline to Week 48
Secondary	Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period	FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.	Baseline to week 48
Secondary	Change in Forced Vital Capacity (FVC) During Double-blind Period	FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Patients perform three to eight exhalations into a spirometer with the highest value recorded.	From Baseline to Week 48
Secondary	Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period	The Health Assessment Questionnaire Disability Index (HAQ-DI) consists of 20 questions referring to eight component sets consisting of dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored on a 4-point scale from 0 to 3: 0 = Without any difficulty; 1 = With some difficulty; 2 = With much difficulty; 3 = Unable to do. Overall score was computed as the sum of component set scores and divided by the number of component sets answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. The total score indicates the patient's self-assessed level of disability. This outcome measure represents the change in mean score from baseline. A negative change from baseline indicates improvement.	From Baseline to Week 48
Secondary	Change in Patient Global Assessment Score During Double-blind Period	The Patient's Global Assessment represents the patient's overall assessment of current SSc status on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating "has no effect at all" (symptom free), and 100 on the extreme right end indicating "worst possible effect."	From Baseline to Week 48
Secondary	Change in Physician Global Assessment Score During Double-blind Period	The Physician's Global Assessment is to be completed on the basis of examination and overall assessment of the patient. The physician's assessment of the patient's SSc status will be scored on a 100-mm horizontal visual analogue scale (VAS), ranging from 0 on the extreme left end of the scale indicating "has no effect at all" (symptom free), and 100 on the extreme right end indicating "worst possible effect."	From Baseline to Week 48
Secondary	Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period	Time to treatment failure is defined as the time from randomization to the time of death, decline in percent-predicted FVC > 10% relative to baseline, > 20% increase in mRSS and an increase in mRSS of equal to or more than 5 points, or occurrence of a predefined SSc-related complication as adjudicated by the Clinical Adjudication Committee (whichever occurs first) during the 48-week double-blind treatment period. The median TTF was not estimable and is not presented for either treatment arm because of the low number of patients with events at Week 48.	From Baseline to Week 48
Secondary	Summary of Adverse Events During Double-blind Period	Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 20.1. NMSC = Non-Melanoma Skin Cancer	From Baseline until Week 48
Secondary	Incidence and Severity of Adverse Events During Double-blind Period	Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.	From Baseline until Week 48
Secondary	Number of Participants With Adverse Events Leading to Death During Double-blind Period	Reason of death is coded using MedDRA 20.1	From Baseline up to Week 48
Secondary	Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period	Adverse event terms coded using MedDRA 20.1. Includes only those serious events adjudicated as SSC-related complications by an independent external committee.	From Baseline up to Week 48
Secondary	Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period	A laboratory event occurred if the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade for a post-baseline laboratory measurement increased from baseline.	From Baseline up to Week 48
Secondary	Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period	A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.	From Baseline to Week 48
Secondary	Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline	Incidence of anti-Tocilizumab at baseline	Baseline
Secondary	Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48	Incidence of anti-Tocilizumab antibodies during the study relative to the prevalence of anti-Tocilizumab antibodies at baseline. Samples that are positive for anti-TCZ in the screening assay will be further analyzed by a confirmation assay to confirm specificity. If the confirmation assay is positive, two additional tests will be performed: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.	Double-blind period (up to Week 48)
Secondary	Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab	Pre-specified analysis of the relationship between Anti-Tocilizumab Antibody status and safety, efficacy, and PK endpoints were not analyzed via subgroup analyses as there was only 1 patient with ADA-positive status.	Baseline; during Weeks 8, 16, 24, 36, 48, 96, and/or at treatment discontinuation (up to 96 weeks); and 8 weeks after treatment discontinuation (up to 104 weeks overall)
Secondary	Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48	Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.	From Predose up to Week 48
Secondary	Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48	Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48	Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48	Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48	Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48	Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48	Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48	Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48	Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48	Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline to Week 48
Secondary	Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48	Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline up to Week 48
Secondary	Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48	Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline up to Week 48
Secondary	Serum Tocilizumab Concentration, Mean, From Baseline to Week 48	Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter	From Baseline to Week 48
Secondary	Serum Tocilizumab Concentration, Median, From Baseline to Week 48	Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter	From Baseline to Week 48
Secondary	Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48	In order to characterize exposure-efficacy relationships, mRSS scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48	In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48	In order to characterize exposure-efficacy relationships, ppFVC scores are summarized based on TCZ exposure tertiles (high, medium, and low exposures) in the active treatment group and compared to placebo patients. Low Exposure = 0-<41 ug/ml, Medium = 41-<=61.1 ug/ml, High = 61.1-<=145 ug/ml.	From Baseline to Week 48
Secondary	Summary of Adverse Events Up to Week 96	Summary of key safety results including Adverse Events of Special Interest (AESI). All adverse events categorized according to MedDRA version 21.1. NMSC = Non-Melanoma Skin Cancer	Up to Week 96
Secondary	Incidence and Severity of Adverse Events Up to Week 96	Adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity grade: 1 = mild, 2 = moderate, 3 = severe and/or requiring medical intervention but not life-threatening, 4 = life-threatening consequences, and 5 = death.	Up to Week 96
Secondary	Number of Participants With Adverse Events Leading to Death Up to Week 96		Up to Week 96
Secondary	Percentage of Participants With Change in Digital Ulcer Count at Week 96	A digital ulcer is defined as an ulcer at or distal to the MCP joint on either the dorsal or volar surface, with loss of surface epithelialization. This does not include fissures, cracks, or calcium extrusions from calcinosis cutis. The number of fingers (0-10) with digital ulcers and the number of digital (or finger) ulcers will be counted and recorded by the investigator.	From Baseline to Week 96
Secondary	Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96	Reported were the percentage of participants with post-baseline treatment-induced anti-TCZ antibodies. Positive samples underwent additional analyses: a neutralizing assay for the ability to inhibit the activity of TCZ and a test for anti -TCZ of the IgE isotype.	Open-label period from Week 48 to 96
Secondary	Erythrocyte Sedimentation Rate (ESR) Up to Week 96	Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.	Up to Week 96
Secondary	Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96	Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.	Up to Week 96
Secondary	Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96	Serum Soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.	Up to Week 96
Secondary	Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96	Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.	From Baseline up to Week 96
Secondary	Serum Tocilizumab Concentration, Mean, Up to Week 96	Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter	Up to Week 96