Systemic SclerosisPhase 3focuSScedNCT02453256
A Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis (SSc)
A Phase 3 study testing Tocilizumab in people with Systemic Sclerosis, run by Hoffmann-La Roche at 83 sites in 22 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 83 sitesin 22 countries
- Study dates
- 20 Nov 2015to 4 Feb 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
83 sites in 22 countries.
83 sites in 22 countries
United States16 sites
University of Michigan
Ann Arbor, Michigan, 48109-0934
Rheumatology Assoc. of S. Florida - Clinical Research Center
Boca Raton, Florida, 33486
Boston Univ Med Center - AC
Boston, Massachusetts, 02118
Joint & Muscle Research Institute
Charlotte, North Carolina, 28204
Metroplex Clinical Research
Dallas, Texas, 75231
TriWest Research Associates, LLC
El Cajon, California, 92020
St. Joseph's Heritage Healthcare
Fullerton, California, 92835
West Michigan Rheumatology, PLLC
Grand Rapids, Michigan, 49546
West Tennessee Research Institute
Jackson, Tennessee, 38305
Univ of Calif., Los Angeles; Rheumatology
Los Angeles, California, 90025
Arthritis Associates of Southern California
Los Angeles, California, 90045
Arthritis and Rheumatology; Center of Oklahoma PLLC
Oklahoma City, Oklahoma, 73103
Millenium Research
Ormond Beach, Florida, 32174
Thomas Jefferson Uni ; Division of Rheumatology
Philadelphia, Pennsylvania, 19131
Georgetown Uni. Hosp.; Rheumatology, Immunology and Allergy Dept.
Washington D.C., District of Columbia, 20007
Clinical Research Center of Reading
Wyomissing, Pennsylvania, 19610
Japan11 sites
Gunma University Hospital
Gunma, 371-8511
Sapporo Medical University Hospital
Hokkaido, 060-8543
Hokkaido University Hospital
Hokkaido, 060-8648
Kanazawa University Hospital
Ishikawa, 920-8641
St. Marianna University School of Medicine Hospital
Kanagawa, 216-8511
Hospital of the University of Occupational and Environmental Health,Japan
Kitakyushu-shi, 807-8556
Kumamoto University Hospital
Kumamoto, 860-8556
Tohoku University Hospital
Miyagi, 980-8574
Osaka University Hospital
Osaka, 565-0871
Nippon Medical School Hospital
Tokyo, 113-8603
The University of Tokyo Hospital
Tokyo, 113-8655
Poland6 sites
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela; Klinika Reumatologii i Ukladowych Chorob
Bydgoszcz, 85-168
Uniwersyteckie Centrum Kliniczne; Klinika Chorob Wewnetrznych, Chorob Tkanki Łacznej i Geriatrii
Gdansk, 80-952
Gornoslaskie Centrum Medyczne
Katowice, 40-635
Szpital Specjalistyczny im Jozefa Dietla; Centrum Reumatologii, Immunologii i Rehabilitacji, I Oddzi
Krakow, 31-121
SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki
Lublin, 20-954
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher
Warsaw, 02-637
United Kingdom6 sites
Queen Elizabeth Hospital; Rheumatology Dept.
Birmingham, B15 2TH
Western General Hospital
Edinburgh, EH4 2XU
Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine
Leeds, LS7 4SA
Uni Hospital Aintree; Academic Rheumatology Unit
Liverpool, L9 7AL
Royal Free Hospital; Department of Rheumatology
London, NW3 2QG
Freeman Hospital; Musculoskeletal Unit
Newcastle upon Tyne, NE7 7DN
Germany5 sites
Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
Bad Abbach, 93077
Kerckhoff-Klinik; Rheumatologie&klin.Immunologie
Bad Nauheim, 61231
Universitätsklinikum Dresden; Technische Universität Dresden; Rheumatologie, Innere Medizin III
Dresden, 01307
Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
München, 80336
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Tübingen, 72076
Argentina4 sites
Organizacion Medica de Investigacion
Buenos Aires, C1015ABO
Hospital Britanico; Haematology
Buenos Aires, C1280AEB
Sanatorio Parque S.A.
Rosario, Santa FE, S2000DSV
Centro de Investigaciones Reumatologicas Tucuman
San Miguel de Tucumán, 4000
Bulgaria4 sites
MHAT Kaspela; Rheumatology
Plovdiv, 4002
MHAT-Plovdiv AD; Reumatology Department
Plovdiv, 4003
MHAT St.Ivan Rilski; Rheumtology Department
Sofia, 1612
MHAT Sv.Ivan Rilski; Clinic of Rheumatology
Sofia, 1612
Italy4 sites
Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia
Florence, Tuscany, 50139
Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica
Milan, Lombardy, 20122
Policlinico Universitario-II Università di Napoli; Reumatologia
Naples, Campania, 80131
Uni ' Cattolica Del Sacro Cuore; Facoltà Di Medicina E Chirurgia A.Gemelli-Clinica Reumatologica
Rome, Lazio, 00168
Mexico3 sites
Unidad De Enfermedades; Cronico Degenerativas, SC.
México, 44620
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
Mexico City, Tlalpan 14000
Cliditer SA de CV
Miexico City, 06700
Spain3 sites
Hospital de la Santa Creu i Sant Pau; Servicio de Medicina Interna/Reumatologia
Barcelona, 08025
Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna
Barcelona, 08035
Hospital General Universitario Gregorio Marañon; Servicio de Reumatología
Madrid, 28007
Canada2 sites
Mount Sinai Hospital; Rebecca Macdonald Centre For Arthritis & Autoimmune Disease
Toronto, Ontario, M5G 1X5
St. Paul's Hospital University of British Colambia Division of Hematology
Vancouver, British Columbia, V6Z 1Y6
Denmark2 sites
Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme
Aarhus N, 8200
Bispebjerg Hospital, Dermatologisk afdeling
København NV, 2400
Greece2 sites
Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens
Athens, 115 27
University Hospital of Patras; Rheumatology
Pátrai, 265 04
Hungary2 sites
National Institute of Rheumatology and Physiology
Budapest, 1023
Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika
Pécs, 7632
Lithuania2 sites
Klaipeda University Hospital; Department of Rheumatology
Klaipėda, LT - 92288
Vilnius University Hospital Santariskiu Clinic Public Insti
Vilnius, 08661
Portugal2 sites
Hospital Garcia de Orta; Servico de Reumatologia
Almada, 2801-951
Hospital Prof. Dr. Fernando Fonseca; Medicina IV
Amadora, 3814-501
Romania2 sites
Cantacuzino Hospital; Department of Internal Medicine and Rheumatology
Bucharest, 020475
Spitalul Judetean Cluj; Sectia de Reumatologie
Cluj-Napoca, 400006
Switzerland2 sites
Universitätsspital Basel; Rheumatologische Poliklinik
Basel, 4031
Universitätsspital Zürich; Klinik für Rheumatologie
Zurich, 8091
Netherlands1 site
Academisch Ziekenhuis Leiden; Dept of Rheumatology
Leiden, 2333 ZA
Puerto Rico1 site
Puerto Rico Clinical & Translational Research Consortium
San Juan, 00936-5067
About this study
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
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.
- Conditions
- Systemic Sclerosis
- Being tested
- Placebo, Tocilizumab
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants will receive matching placebo subcutaneous (SC) injections once weekly for 48 weeks of double-blind treatment.
TocilizumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind Placebo | Placebo comparator | Participants will receive double-blind matching placebo from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96. Receives: Drug: Placebo; Drug: Tocilizumab |
| Double-Blind Tocilizumab | Experimental | Participants will receive double-blind tocilizumab from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96. Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to week 48
Secondary outcomes (50)
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.
Measured: From Baseline to Week 48
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.
Measured: Baseline to week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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."
Measured: From Baseline to Week 48
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."
Measured: From Baseline to Week 48
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.
Measured: From Baseline to 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
Measured: From Baseline until Week 48
Incidence and Severity of Adverse Events During Double-blind Period
Adverse events listed according to MedDRA version 20.1 preferred terms and severity grade.
Measured: From Baseline until Week 48
Number of Participants With Adverse Events Leading to Death During Double-blind Period
Reason of death is coded using MedDRA 20.1
Measured: From Baseline up to Week 48
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.
Measured: From Baseline up to Week 48
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.
Measured: From Baseline up to Week 48
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.
Measured: From Baseline to Week 48
Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline
Incidence of anti-Tocilizumab at baseline
Measured: 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.
Measured: Double-blind period (up to Week 48)
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.
Measured: 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)
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.
Measured: From Predose up to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline up to Week 48
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.
Measured: From Baseline up to Week 48
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Measured: From Baseline to Week 48
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: From Baseline to Week 48
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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.
Measured: From Baseline to Week 48
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.
Measured: 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
Measured: Up to Week 96
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.
Measured: Up to Week 96
Number of Participants With Adverse Events Leading to Death Up to Week 96
Measured: Up to Week 96
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.
Measured: From Baseline to 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.
Measured: Open-label period from Week 48 to 96
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.
Measured: Up to Week 96
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.
Measured: Up to Week 96
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.
Measured: Up to Week 96
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.
Measured: From Baseline up to Week 96
Serum Tocilizumab Concentration, Mean, Up to Week 96
Predose observed serum TCZ concentration at baseline and at specified timepoints thereafter
Measured: Up to Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2015 (estimated)
- Study start20 Nov 2015
- Primary completion15 Jan 2018
- Study completion4 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453256
- Sponsor's protocol ID
- WA29767
- Other IDs
- 2015-000424-28, 2015
- Acronym
- focuSSced
- Status last verified
- Mar 2020
- First submitted
- 21 May 2015
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ghuman A, Khanna D, Lin CJF, Furst DE, Raghu G, Martinez FJ, Zucchetto M, Huang S, Jennings A, Nihtyanova SI, Denton CP. Prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease in a clinical trial and long-term observational cohort. Rheumatology (Oxford). 2024 Feb 1;63(2):472-481. doi: 10.1093/rheumatology/kead234.
PubMed 37228011Khanna 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.
PubMed 34851799Roofeh 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.
PubMed 33538094Gao 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.
PubMed 33294861Khanna 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.
PubMed 32866440
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02453256
- Acronym / sponsor ID
- focuSSced / WA29767
- Conditions
- Systemic Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 212 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 20 Nov 2015 (actual)
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 4 Feb 2019 (actual)
- First posted
- 25 May 2015 (estimated)
- Results
- Posted 3 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Placebo | Placebo comparator | Drug: Placebo, Drug: TocilizumabParticipants will receive double-blind matching placebo from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96. |
| Double-Blind Tocilizumab | Experimental | Drug: TocilizumabParticipants will receive double-blind tocilizumab from Baseline to Week 47. Participants may then receive open-label tocilizumab from Weeks 48 to 96. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboParticipants will receive matching placebo subcutaneous (SC) injections once weekly for 48 weeks of double-blind treatment. | Drug | Double-Blind Placebo |
| TocilizumabParticipants 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. | Drug | Double-Blind Placebo, Double-Blind Tocilizumab |
Primary outcome
Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period
Time frame: From baseline to week 48
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.
50 secondary outcomes
Percentage of Participants With Greater Than or Equal to (>/=) 20%, 40%, or 60% Improvement in mRSS During Double-blind Period
Time frame: From Baseline to Week 48
Change From Baseline in Percent Predicted FVC (ppFVC) During Double-blind Period
Time frame: Baseline to week 48
Change in Forced Vital Capacity (FVC) During Double-blind Period
Time frame: From Baseline to Week 48
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) Score During Double-blind Period
Time frame: From Baseline to Week 48
Change in Patient Global Assessment Score During Double-blind Period
Time frame: From Baseline to Week 48
Change in Physician Global Assessment Score During Double-blind Period
Time frame: From Baseline to Week 48
Time to Treatment Failure According to mRSS, FVC, or Protocol-Specified Event During Double-blind Period
Time frame: From Baseline to Week 48
Summary of Adverse Events During Double-blind Period
Time frame: From Baseline until Week 48
Incidence and Severity of Adverse Events During Double-blind Period
Time frame: From Baseline until Week 48
Number of Participants With Adverse Events Leading to Death During Double-blind Period
Time frame: From Baseline up to Week 48
Frequency of Serious Systemic Sclerosis (SSC) Related Complications During Double-blind Period
Time frame: From Baseline up to Week 48
Incidence of Haematology and Hepatic Laboratory Parameters During Double-blind Period
Time frame: From Baseline up to Week 48
Percentage of Participants With Change in Digital Ulcer Count During Double-blind Period
Time frame: From Baseline to Week 48
Percentage of Participants With Positive Anti-Tocilizumab Assay Result at Baseline
Time frame: Baseline
Percentage of Participants With Positive Anti-Tocilizumab Assay Post-Baseline up to Week 48
Time frame: Double-blind period (up to Week 48)
Correlation Between Anti-Tocilizumab Antibody Status and Outcome Measures Pertaining to the Efficacy, Safety, and Pharmacokinetics of Tocilizumab
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)
Erythrocyte Sedimentation Rate (ESR), Mean, From Baseline to Week 48
Time frame: From Predose up to Week 48
Erythrocyte Sedimentation Rate (ESR), Median, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Interleukin (IL)-6 Level, Mean, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Interleukin (IL)-6 Level, Median, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Interleukin (IL)-6 Level, Mean Change From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Interleukin (IL)-6 Level, Median Change From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Soluble Interleukin (IL)-6 Receptor Level, Median, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Soluble Interleukin (IL)-6 Receptor Level, Mean Change From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Soluble Interleukin (IL)-6 Receptor Level, Median Change From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum C-Reactive Protein (CRP) Level, Mean, From Baseline to Week 48
Time frame: From Baseline up to Week 48
Serum C-Reactive Protein (CRP) Level, Median, From Baseline to Week 48
Time frame: From Baseline up to Week 48
Serum Tocilizumab Concentration, Mean, From Baseline to Week 48
Time frame: From Baseline to Week 48
Serum Tocilizumab Concentration, Median, From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between Low Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between Low Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between Medium Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between Medium Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between High Serum Tocilizumab Exposure and Mean Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: From Baseline to Week 48
Correlation Between High Serum Tocilizumab Exposure and Median Modified Rodnan Skin Score (mRSS) From Baseline to Week 48
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From Baseline to Week 48
Change in Median Percent Predicted Forced Vital Capacity (ppFVC), at Low, Medium and High Serum Tocilizumab Exposure From Baseline to Week 48
Time frame: From Baseline to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37228011Ghuman A, Khanna D, Lin CJF, Furst DE, Raghu G, Martinez FJ, Zucchetto M, Huang S, Jennings A, Nihtyanova SI, Denton CP. Prognostic and predictive markers of systemic sclerosis-associated interstitial lung disease in a clinical trial and long-term observational cohort. Rheumatology (Oxford). 2024 Feb 1;63(2):472-481. doi: 10.1093/rheumatology/kead234.
- Derived from this study: PubMed 34851799Khanna 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.
- Derived from this study: PubMed 33538094Roofeh 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.
- Derived from this study: PubMed 33294861Gao 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.
- Derived from this study: PubMed 32866440Khanna 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
83 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab in people with Systemic Sclerosis, run by Hoffmann-La Roche at 83 sites in 22 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 83 sites in United States, Japan, Poland, United Kingdom, Germany and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Modified Rodnan Skin Score (mRSS) During Double-blind Period (time frame: From baseline to week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02453256, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.