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

Primary Purpose

Systemic Sclerosis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Placebo

Tocilizumab

About this trial

This is an interventional treatment trial for Systemic Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

TriWest Research Associates, LLC
St. Joseph's Heritage Healthcare
Univ of Calif., Los Angeles; Rheumatology
Arthritis Associates of Southern California
Georgetown Uni. Hosp.; Rheumatology, Immunology and Allergy Dept.
Rheumatology Assoc. of S. Florida - Clinical Research Center
Millenium Research
Boston Univ Med Center - AC
University of Michigan
West Michigan Rheumatology, PLLC
Joint & Muscle Research Institute
Arthritis and Rheumatology; Center of Oklahoma PLLC
Thomas Jefferson Uni ; Division of Rheumatology
Clinical Research Center of Reading
West Tennessee Research Institute
Metroplex Clinical Research
Organizacion Medica de Investigacion
Hospital Britanico; Haematology
Sanatorio Parque S.A.
Centro de Investigaciones Reumatologicas Tucuman
UZ Gent
UZ Leuven Gasthuisberg
MHAT Kaspela; Rheumatology
MHAT-Plovdiv AD; Reumatology Department
MHAT St.Ivan Rilski; Rheumtology Department
MHAT Sv.Ivan Rilski; Clinic of Rheumatology
St. Paul's Hospital University of British Colambia Division of Hematology
Mount Sinai Hospital; Rebecca Macdonald Centre For Arthritis & Autoimmune Disease
Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme
Bispebjerg Hospital, Dermatologisk afdeling
Hopital Claude Huriez; Internal Medicine
Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
Kerckhoff-Klinik; Rheumatologie&klin.Immunologie
Universitätsklinikum Dresden; Technische Universität Dresden; Rheumatologie, Innere Medizin III
Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens
University Hospital of Patras; Rheumatology
National Institute of Rheumatology and Physiology
Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika
Policlinico Universitario-II Università di Napoli; Reumatologia
Uni ' Cattolica Del Sacro Cuore; Facoltà Di Medicina E Chirurgia A.Gemelli-Clinica Reumatologica
Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica
Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia
Gunma University Hospital
Sapporo Medical University Hospital
Hokkaido University Hospital
Kanazawa University Hospital
St. Marianna University School of Medicine Hospital
Hospital of the University of Occupational and Environmental Health,Japan
Kumamoto University Hospital
Tohoku University Hospital
Osaka University Hospital
Nippon Medical School Hospital
The University of Tokyo Hospital
Klaipeda University Hospital; Department of Rheumatology
Vilnius University Hospital Santariskiu Clinic Public Insti
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
Unidad De Enfermedades; Cronico Degenerativas, SC.
Cliditer SA de CV
Academisch Ziekenhuis Leiden; Dept of Rheumatology
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob
Uniwersyteckie Centrum Kliniczne; Klinika Chorob Wewnetrznych, Chorob Tkanki Łacznej i Geriatrii
Gornoslaskie Centrum Medyczne
Szpital Specjalistyczny im Jozefa Dietla; Centrum Reumatologii, Immunologii i Rehabilitacji, I Oddzi
SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher
Hospital Garcia de Orta; Servico de Reumatologia
Hospital Prof. Dr. Fernando Fonseca; Medicina IV
Puerto Rico Clinical & Translational Research Consortium
Cantacuzino Hospital; Department of Internal Medicine and Rheumatology
Spitalul Judetean Cluj; Sectia de Reumatologie
Hospital de la Santa Creu i Sant Pau; Servicio de Medicina Interna/Reumatologia
Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna
Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
Universitätsspital Basel; Rheumatologische Poliklinik
Universitätsspital Zürich; Klinik für Rheumatologie
Queen Elizabeth Hospital; Rheumatology Dept.
Western General Hospital
Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine
Uni Hospital Aintree; Academic Rheumatology Unit
Royal Free Hospital; Department of Rheumatology
Freeman Hospital; Musculoskeletal Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Double-Blind Placebo

Double-Blind Tocilizumab

Arm Description

Participants will receive double-blind matching placebo from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96.

Participants will receive double-blind tocilizumab from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Change in Forced Vital Capacity (FVC) During Double-blind Period

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.

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."

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."

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.

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

Incidence and Severity of Adverse Events During Double-blind Period

Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.

Number of Participants With Adverse Events Leading to Death During Double-blind Period

Reason of death is coded using MedDRA 20.1

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.

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.

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.

Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline

Incidence of anti-Tocilizumab at baseline

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Serum Tocilizumab Concentration, Mean, From Baseline to Week 48

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

Serum Tocilizumab Concentration, Median, From Baseline to Week 48

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

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.

Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

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.

Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

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

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.

Number of Participants With Adverse Events Leading to Death Up to Week 96

Percentage of Participants With Change in Digital Ulcer Count at Week 96

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.

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.

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.

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.

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.

Serum Tocilizumab Concentration, Mean, Up to Week 96

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

Full Information

NCT ID

NCT02453256

First Posted

May 21, 2015

Last Updated

March 5, 2020

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02453256

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

November 20, 2015 (Actual)

Primary Completion Date

January 15, 2018 (Actual)

Study Completion Date

February 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

212 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Double-Blind Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will receive double-blind matching placebo from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96.

Arm Title

Double-Blind Tocilizumab

Arm Type

Experimental

Arm Description

Participants will receive double-blind tocilizumab from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive matching placebo subcutaneous (SC) injections once weekly for 48 weeks of double-blind treatment.

Intervention Type

Drug

Intervention Name(s)

Tocilizumab

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period

Description

Time Frame

From baseline to week 48

Secondary Outcome Measure Information:

Title

Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period

Description

The proportion of participants with threshold improvements in mRSS at Week 48 relative to baseline.

Time Frame

From Baseline to Week 48

Title

Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period

Description

Time Frame

Baseline to week 48

Title

Change in Forced Vital Capacity (FVC) During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Change in Patient Global Assessment Score During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Change in Physician Global Assessment Score During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Summary of Adverse Events During Double-blind Period

Description

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

Time Frame

From Baseline until Week 48

Title

Incidence and Severity of Adverse Events During Double-blind Period

Description

Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.

Time Frame

From Baseline until Week 48

Title

Number of Participants With Adverse Events Leading to Death During Double-blind Period

Description

Reason of death is coded using MedDRA 20.1

Time Frame

From Baseline up to Week 48

Title

Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period

Description

Adverse event terms coded using MedDRA 20.1. Includes only those serious events adjudicated as SSC-related complications by an independent external committee.

Time Frame

From Baseline up to Week 48

Title

Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period

Description

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.

Time Frame

From Baseline up to Week 48

Title

Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period

Description

Time Frame

From Baseline to Week 48

Title

Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline

Description

Incidence of anti-Tocilizumab at baseline

Time Frame

Baseline

Title

Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48

Description

Time Frame

Double-blind period (up to Week 48)

Title

Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab

Description

Time Frame

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)

Title

Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48

Description

Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Predose up to Week 48

Title

Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48

Description

Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48

Description

Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48

Description

Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48

Description

Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48

Description

Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48

Description

Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48

Description

Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48

Description

Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48

Description

Serum soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline to Week 48

Title

Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48

Description

Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline up to Week 48

Title

Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48

Description

Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline up to Week 48

Title

Serum Tocilizumab Concentration, Mean, From Baseline to Week 48

Description

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

Time Frame

From Baseline to Week 48

Title

Serum Tocilizumab Concentration, Median, From Baseline to Week 48

Description

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

Time Frame

From Baseline to Week 48

Title

Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Change in Mean Modified Rodnan Skin Score (mRSS) at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Change in Median Modified Rodnan Skin Score (mRSS), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Change in Mean Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48

Description

Time Frame

From Baseline to Week 48

Title

Summary of Adverse Events Up to Week 96

Description

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

Time Frame

Up to Week 96

Title

Incidence and Severity of Adverse Events Up to Week 96

Description

Time Frame

Up to Week 96

Title

Number of Participants With Adverse Events Leading to Death Up to Week 96

Time Frame

Up to Week 96

Title

Percentage of Participants With Change in Digital Ulcer Count at Week 96

Description

Time Frame

From Baseline to Week 96

Title

Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline From Week 48 to 96

Description

Time Frame

Open-label period from Week 48 to 96

Title

Erythrocyte Sedimentation Rate (ESR) Up to Week 96

Description

Erythrocyte Sedimentation Rate (ESR) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

Up to Week 96

Title

Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 96

Description

Serum Interleukin (IL)-6 levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

Up to Week 96

Title

Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, Up to Week 96

Description

Serum Soluble Interleukin (IL)-6 receptor levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

Up to Week 96

Title

Serum C-Reactive Protein (CRP) Level, Mean, Up to Week 96

Description

Serum C-Reactive Protein (CRP) levels predose at baseline and at subsequent time points after initiation of study drug.

Time Frame

From Baseline up to Week 96

Title

Serum Tocilizumab Concentration, Mean, Up to Week 96

Description

Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter

Time Frame

Up to Week 96

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

TriWest Research Associates, LLC

City

El Cajon

State/Province

California

ZIP/Postal Code

92020

Country

United States

Facility Name

St. Joseph's Heritage Healthcare

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Facility Name

Univ of Calif., Los Angeles; Rheumatology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90025

Country

United States

Facility Name

Arthritis Associates of Southern California

City

Los Angeles

State/Province

California

ZIP/Postal Code

90045

Country

United States

Facility Name

Georgetown Uni. Hosp.; Rheumatology, Immunology and Allergy Dept.

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Rheumatology Assoc. of S. Florida - Clinical Research Center

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33486

Country

United States

Facility Name

Millenium Research

City

Ormond Beach

State/Province

Florida

ZIP/Postal Code

32174

Country

United States

Facility Name

Boston Univ Med Center - AC

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109-0934

Country

United States

Facility Name

West Michigan Rheumatology, PLLC

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49546

Country

United States

Facility Name

Joint & Muscle Research Institute

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

Arthritis and Rheumatology; Center of Oklahoma PLLC

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73103

Country

United States

Facility Name

Thomas Jefferson Uni ; Division of Rheumatology

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19131

Country

United States

Facility Name

Clinical Research Center of Reading

City

Wyomissing

State/Province

Pennsylvania

ZIP/Postal Code

19610

Country

United States

Facility Name

West Tennessee Research Institute

City

Jackson

State/Province

Tennessee

ZIP/Postal Code

38305

Country

United States

Facility Name

Metroplex Clinical Research

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Organizacion Medica de Investigacion

City

Buenos Aires

ZIP/Postal Code

C1015ABO

Country

Argentina

Facility Name

Hospital Britanico; Haematology

City

Buenos Aires

ZIP/Postal Code

C1280AEB

Country

Argentina

Facility Name

Sanatorio Parque S.A.

City

Rosario, Santa FE

ZIP/Postal Code

S2000DSV

Country

Argentina

Facility Name

Centro de Investigaciones Reumatologicas Tucuman

City

Tucuman

ZIP/Postal Code

4000

Country

Argentina

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

UZ Leuven Gasthuisberg

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

MHAT Kaspela; Rheumatology

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

MHAT-Plovdiv AD; Reumatology Department

City

Plovdiv

ZIP/Postal Code

4003

Country

Bulgaria

Facility Name

MHAT St.Ivan Rilski; Rheumtology Department

City

Sofia

ZIP/Postal Code

1612

Country

Bulgaria

Facility Name

MHAT Sv.Ivan Rilski; Clinic of Rheumatology

City

Sofia

ZIP/Postal Code

1612

Country

Bulgaria

Facility Name

St. Paul's Hospital University of British Colambia Division of Hematology

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6Z 1Y6

Country

Canada

Facility Name

Mount Sinai Hospital; Rebecca Macdonald Centre For Arthritis & Autoimmune Disease

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X5

Country

Canada

Facility Name

Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme

City

Aarhus N

ZIP/Postal Code

8200

Country

Denmark

Facility Name

Bispebjerg Hospital, Dermatologisk afdeling

City

København NV

ZIP/Postal Code

2400

Country

Denmark

Facility Name

Hopital Claude Huriez; Internal Medicine

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

City

Bad Abbach

ZIP/Postal Code

93077

Country

Germany

Facility Name

Kerckhoff-Klinik; Rheumatologie&klin.Immunologie

City

Bad Nauheim

ZIP/Postal Code

61231

Country

Germany

Facility Name

Universitätsklinikum Dresden; Technische Universität Dresden; Rheumatologie, Innere Medizin III

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV

City

München

ZIP/Postal Code

80336

Country

Germany

Facility Name

Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens

City

Athens

ZIP/Postal Code

115 27

Country

Greece

Facility Name

University Hospital of Patras; Rheumatology

City

Patras

ZIP/Postal Code

265 04

Country

Greece

Facility Name

National Institute of Rheumatology and Physiology

City

Budapest

ZIP/Postal Code

1023

Country

Hungary

Facility Name

Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika

City

Pécs

ZIP/Postal Code

7632

Country

Hungary

Facility Name

Policlinico Universitario-II Università di Napoli; Reumatologia

City

Napoli

State/Province

Campania

ZIP/Postal Code

80131

Country

Italy

Facility Name

Uni ' Cattolica Del Sacro Cuore; Facoltà Di Medicina E Chirurgia A.Gemelli-Clinica Reumatologica

City

Roma

State/Province

Lazio

ZIP/Postal Code

00168

Country

Italy

Facility Name

Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20122

Country

Italy

Facility Name

Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia

City

Firenze

State/Province

Toscana

ZIP/Postal Code

50139

Country

Italy

Facility Name

Gunma University Hospital

City

Gunma

ZIP/Postal Code

371-8511

Country

Japan

Facility Name

Sapporo Medical University Hospital

City

Hokkaido

ZIP/Postal Code

060-8543

Country

Japan

Facility Name

Hokkaido University Hospital

City

Hokkaido

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

Kanazawa University Hospital

City

Ishikawa

ZIP/Postal Code

920-8641

Country

Japan

Facility Name

St. Marianna University School of Medicine Hospital

City

Kanagawa

ZIP/Postal Code

216-8511

Country

Japan

Facility Name

Hospital of the University of Occupational and Environmental Health,Japan

City

Kitakyushu-shi

ZIP/Postal Code

807-8556

Country

Japan

Facility Name

Kumamoto University Hospital

City

Kumamoto

ZIP/Postal Code

860-8556

Country

Japan

Facility Name

Tohoku University Hospital

City

Miyagi

ZIP/Postal Code

980-8574

Country

Japan

Facility Name

Osaka University Hospital

City

Osaka

ZIP/Postal Code

565-0871

Country

Japan

Facility Name

Nippon Medical School Hospital

City

Tokyo

ZIP/Postal Code

113-8603

Country

Japan

Facility Name

The University of Tokyo Hospital

City

Tokyo

ZIP/Postal Code

113-8655

Country

Japan

Facility Name

Klaipeda University Hospital; Department of Rheumatology

City

Klaipeda

ZIP/Postal Code

LT - 92288

Country

Lithuania

Facility Name

Vilnius University Hospital Santariskiu Clinic Public Insti

City

Vilnius

ZIP/Postal Code

08661

Country

Lithuania

Facility Name

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

City

Mexico City

ZIP/Postal Code

Tlalpan 14000

Country

Mexico

Facility Name

Unidad De Enfermedades; Cronico Degenerativas, SC.

City

Mexico

ZIP/Postal Code

44620

Country

Mexico

Facility Name

Cliditer SA de CV

City

Miexico City

ZIP/Postal Code

06700

Country

Mexico

Facility Name

Academisch Ziekenhuis Leiden; Dept of Rheumatology

City

Leiden

ZIP/Postal Code

2333 ZA

Country

Netherlands

Facility Name

Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob

City

Bydgoszcz

ZIP/Postal Code

85-168

Country

Poland

Facility Name

Uniwersyteckie Centrum Kliniczne; Klinika Chorob Wewnetrznych, Chorob Tkanki Łacznej i Geriatrii

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Gornoslaskie Centrum Medyczne

City

Katowice

ZIP/Postal Code

40-635

Country

Poland

Facility Name

Szpital Specjalistyczny im Jozefa Dietla; Centrum Reumatologii, Immunologii i Rehabilitacji, I Oddzi

City

Krakow

ZIP/Postal Code

31-121

Country

Poland

Facility Name

SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki

City

Lublin

ZIP/Postal Code

20-954

Country

Poland

Facility Name

Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher

City

Warszawa

ZIP/Postal Code

02-637

Country

Poland

Facility Name

Hospital Garcia de Orta; Servico de Reumatologia

City

Almada

ZIP/Postal Code

2801-951

Country

Portugal

Facility Name

Hospital Prof. Dr. Fernando Fonseca; Medicina IV

City

Amadora

ZIP/Postal Code

3814-501

Country

Portugal

Facility Name

Puerto Rico Clinical & Translational Research Consortium

City

San Juan

ZIP/Postal Code

00936-5067

Country

Puerto Rico

Facility Name

Cantacuzino Hospital; Department of Internal Medicine and Rheumatology

City

Bucharest

ZIP/Postal Code

020475

Country

Romania

Facility Name

Spitalul Judetean Cluj; Sectia de Reumatologie

City

Cluj-napoca

ZIP/Postal Code

400006

Country

Romania

Facility Name

Hospital de la Santa Creu i Sant Pau; Servicio de Medicina Interna/Reumatologia

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Facility Name

Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Universitätsspital Basel; Rheumatologische Poliklinik

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Universitätsspital Zürich; Klinik für Rheumatologie

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

Queen Elizabeth Hospital; Rheumatology Dept.

City

Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

Western General Hospital

City

Edinburgh

ZIP/Postal Code

EH4 2XU

Country

United Kingdom

Facility Name

Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine

City

Leeds

ZIP/Postal Code

LS7 4SA

Country

United Kingdom

Facility Name

Uni Hospital Aintree; Academic Rheumatology Unit

City

Liverpool

ZIP/Postal Code

L9 7AL

Country

United Kingdom

Facility Name

Royal Free Hospital; Department of Rheumatology

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Facility Name

Freeman Hospital; Musculoskeletal Unit

City

Newcastle Upon Tyne

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

34851799

Citation

Khanna D, Lin CJF, Furst DE, Wagner B, Zucchetto M, Raghu G, Martinez FJ, Goldin J, Siegel J, Denton CP. Long-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis-Interstitial Lung Disease: Open-Label Extension of a Phase 3 Randomized Controlled Trial. Am J Respir Crit Care Med. 2022 Mar 15;205(6):674-684. doi: 10.1164/rccm.202103-0714OC.

Results Reference

derived

PubMed Identifier

33538094

Citation

Roofeh D, Lin CJF, Goldin J, Kim GH, Furst DE, Denton CP, Huang S, Khanna D; focuSSced Investigators. Tocilizumab Prevents Progression of Early Systemic Sclerosis-Associated Interstitial Lung Disease. Arthritis Rheumatol. 2021 Jul;73(7):1301-1310. doi: 10.1002/art.41668. Epub 2021 May 25.

Results Reference

derived

PubMed Identifier

33294861

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.

Results Reference

derived

PubMed Identifier

32866440

Citation

Khanna D, Lin CJF, Furst DE, Goldin J, Kim G, Kuwana M, Allanore Y, Matucci-Cerinic M, Distler O, Shima Y, van Laar JM, Spotswood H, Wagner B, Siegel J, Jahreis A, Denton CP; focuSSced investigators. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2020 Oct;8(10):963-974. doi: 10.1016/S2213-2600(20)30318-0. Epub 2020 Aug 28. Erratum In: Lancet Respir Med. 2020 Oct;8(10):e75. Lancet Respir Med. 2021 Mar;9(3):e29.

Results Reference

derived

Learn more about this trial

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

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