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

NCT02453256 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: WA297672015-000424-28
• Study Type: interventional
• Target: 212
• Locations: 22 countries
• Sites: 83

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.

Conditions

Systemic Sclerosis

Outcome Measures

Primary Outcomes (1)

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

  The efficacy of TCZ vs placebo is evaluated in terms of in mean change in mRSS. Skin thickness will be assessed by palpation and rated using an mRSS that ranges from 0 (normal) to 3 (severe skin thickening) across 17 different body sites. The total score is the sum of the individual skin scores from all of these sites and ranges from 0 to 51 units.

  From baseline to week 48

Secondary Outcomes (50)

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

  From Baseline to Week 48

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

  Baseline to week 48

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

  From Baseline to Week 48

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

  From Baseline to Week 48

• Change in Patient Global Assessment Score During Double-blind Period

  From Baseline to Week 48

Study Arms (2)

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.

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.

Drug: Tocilizumab

Interventions

Placebo DRUG

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

Double-Blind Placebo

Tocilizumab DRUG

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.

Double-Blind Placebo; Double-Blind Tocilizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (83)

TriWest Research Associates, LLC

El Cajon, California, 92020, United States

Location

St. Joseph's Heritage Healthcare

Fullerton, California, 92835, United States

Location

Univ of Calif., Los Angeles; Rheumatology

Los Angeles, California, 90025, United States

Location

Arthritis Associates of Southern California

Los Angeles, California, 90045, United States

Location

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

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

Location

Rheumatology Assoc. of S. Florida - Clinical Research Center

Boca Raton, Florida, 33486, United States

Location

Millenium Research

Ormond Beach, Florida, 32174, United States

Location

Boston Univ Med Center - AC

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-0934, United States

Location

West Michigan Rheumatology, PLLC

Grand Rapids, Michigan, 49546, United States

Location

Joint & Muscle Research Institute

Charlotte, North Carolina, 28204, United States

Location

Arthritis and Rheumatology; Center of Oklahoma PLLC

Oklahoma City, Oklahoma, 73103, United States

Location

Thomas Jefferson Uni ; Division of Rheumatology

Philadelphia, Pennsylvania, 19131, United States

Location

Clinical Research Center of Reading

Wyomissing, Pennsylvania, 19610, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Metroplex Clinical Research

Dallas, Texas, 75231, United States

Location

Organizacion Medica de Investigacion

Buenos Aires, C1015ABO, Argentina

Location

Hospital Britanico; Haematology

Buenos Aires, C1280AEB, Argentina

Location

Sanatorio Parque S.A.

Rosario, Santa FE, S2000DSV, Argentina

Location

Centro de Investigaciones Reumatologicas Tucuman

San Miguel de Tucumán, 4000, Argentina

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

MHAT Kaspela; Rheumatology

Plovdiv, 4002, Bulgaria

Location

MHAT-Plovdiv AD; Reumatology Department

Plovdiv, 4003, Bulgaria

Location

MHAT St.Ivan Rilski; Rheumtology Department

Sofia, 1612, Bulgaria

Location

MHAT Sv.Ivan Rilski; Clinic of Rheumatology

Sofia, 1612, Bulgaria

Location

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

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

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

Toronto, Ontario, M5G 1X5, Canada

Location

Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme

Aarhus N, 8200, Denmark

Location

Bispebjerg Hospital, Dermatologisk afdeling

København NV, 2400, Denmark

Location

Hopital Claude Huriez; Internal Medicine

Lille, 59037, France

Location

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

Bad Abbach, 93077, Germany

Location

Kerckhoff-Klinik; Rheumatologie&klin.Immunologie

Bad Nauheim, 61231, Germany

Location

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

Dresden, 01307, Germany

Location

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

München, 80336, Germany

Location

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

Tübingen, 72076, Germany

Location

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

Athens, 115 27, Greece

Location

University Hospital of Patras; Rheumatology

Pátrai, 265 04, Greece

Location

National Institute of Rheumatology and Physiology

Budapest, 1023, Hungary

Location

Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika

Pécs, 7632, Hungary

Location

Policlinico Universitario-II Università di Napoli; Reumatologia

Napoli, Campania, 80131, Italy

Location

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

Rome, Lazio, 00168, Italy

Location

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

Milan, Lombardy, 20122, Italy

Location

Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia

Florence, Tuscany, 50139, Italy

Location

Gunma University Hospital

Gunma, 371-8511, Japan

Location

Sapporo Medical University Hospital

Hokkaido, 060-8543, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Kanazawa University Hospital

Ishikawa, 920-8641, Japan

Location

St. Marianna University School of Medicine Hospital

Kanagawa, 216-8511, Japan

Location

Hospital of the University of Occupational and Environmental Health,Japan

Kitakyushu-shi, 807-8556, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Nippon Medical School Hospital

Tokyo, 113-8603, Japan

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Klaipeda University Hospital; Department of Rheumatology

Klaipėda, LT - 92288, Lithuania

Location

Vilnius University Hospital Santariskiu Clinic Public Insti

Vilnius, 08661, Lithuania

Location

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

Mexico City, Tlalpan 14000, Mexico

Location

Unidad De Enfermedades; Cronico Degenerativas, SC.

México, 44620, Mexico

Location

Cliditer SA de CV

Miexico City, 06700, Mexico

Location

Academisch Ziekenhuis Leiden; Dept of Rheumatology

Leiden, 2333 ZA, Netherlands

Location

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

Bydgoszcz, 85-168, Poland

Location

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

Gdansk, 80-952, Poland

Location

Gornoslaskie Centrum Medyczne

Katowice, 40-635, Poland

Location

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

Krakow, 31-121, Poland

Location

SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki

Lublin, 20-954, Poland

Location

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

Warsaw, 02-637, Poland

Location

Hospital Garcia de Orta; Servico de Reumatologia

Almada, 2801-951, Portugal

Location

Hospital Prof. Dr. Fernando Fonseca; Medicina IV

Amadora, 3814-501, Portugal

Location

Puerto Rico Clinical & Translational Research Consortium

San Juan, 00936-5067, Puerto Rico

Location

Cantacuzino Hospital; Department of Internal Medicine and Rheumatology

Bucharest, 020475, Romania

Location

Spitalul Judetean Cluj; Sectia de Reumatologie

Cluj-Napoca, 400006, Romania

Location

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

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

Madrid, 28007, Spain

Location

Universitätsspital Basel; Rheumatologische Poliklinik

Basel, 4031, Switzerland

Location

Universitätsspital Zürich; Klinik für Rheumatologie

Zurich, 8091, Switzerland

Location

Queen Elizabeth Hospital; Rheumatology Dept.

Birmingham, B15 2TH, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine

Leeds, LS7 4SA, United Kingdom

Location

Uni Hospital Aintree; Academic Rheumatology Unit

Liverpool, L9 7AL, United Kingdom

Location

Royal Free Hospital; Department of Rheumatology

London, NW3 2QG, United Kingdom

Location

Freeman Hospital; Musculoskeletal Unit

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 37228011 DERIVED

• 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.

  PMID: 34851799 DERIVED

• 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.

  PMID: 33538094 DERIVED

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

  PMID: 33294861 DERIVED

• 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.

  PMID: 32866440 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2015
• First Posted: May 25, 2015
• Study Start: November 20, 2015
• Primary Completion: January 15, 2018
• Study Completion: February 4, 2019
• Last Updated: March 9, 2020
• Results First Posted: April 3, 2019

Record last verified: 2020-03

Locations

US (16); PR (1); LI (2); HU (2); NL (1); RO (2); BU (4); GR (2); AR (4); DE (5); IT (4); PT (2); ES (3); PL (6); FR (1); ME (3); JP (11); GB (6); CA (2); CH (2); DK (2); BE (2)