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

NCT ID: NCT02453256

Last Updated: 2020-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-20
• Study Completion Date: 2019-02-04

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Double-Blind Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Tocilizumab

Intervention Type: 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 Tocilizumab

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

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: 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.

Interventions

Placebo

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

Intervention Type: DRUG

Tocilizumab

Participants will receive 162 mg SC tocilizumab once weekly for 48 weeks of double-blind treatment. The same regimen will be given to all eligible participants for 48 weeks of open-label treatment.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

TriWest Research Associates, LLC

El Cajon, California, United States

St. Joseph's Heritage Healthcare

Fullerton, California, United States

Univ of Calif., Los Angeles; Rheumatology

Los Angeles, California, United States

Arthritis Associates of Southern California

Los Angeles, California, United States

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

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

Rheumatology Assoc. of S. Florida - Clinical Research Center

Boca Raton, Florida, United States

Millenium Research

Ormond Beach, Florida, United States

Boston Univ Med Center - AC

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

West Michigan Rheumatology, PLLC

Grand Rapids, Michigan, United States

Joint & Muscle Research Institute

Charlotte, North Carolina, United States

Arthritis and Rheumatology; Center of Oklahoma PLLC

Oklahoma City, Oklahoma, United States

Thomas Jefferson Uni ; Division of Rheumatology

Philadelphia, Pennsylvania, United States

Clinical Research Center of Reading

Wyomissing, Pennsylvania, United States

West Tennessee Research Institute

Jackson, Tennessee, United States

Metroplex Clinical Research

Dallas, Texas, United States

Organizacion Medica de Investigacion

Buenos Aires, , Argentina

Hospital Britanico; Haematology

Buenos Aires, , Argentina

Sanatorio Parque S.A.

Rosario, Santa FE, , Argentina

Centro de Investigaciones Reumatologicas Tucuman

San Miguel de Tucumán, , Argentina

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

MHAT Kaspela; Rheumatology

Plovdiv, , Bulgaria

MHAT-Plovdiv AD; Reumatology Department

Plovdiv, , Bulgaria

MHAT St.Ivan Rilski; Rheumtology Department

Sofia, , Bulgaria

MHAT Sv.Ivan Rilski; Clinic of Rheumatology

Sofia, , Bulgaria

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

Vancouver, British Columbia, Canada

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

Toronto, Ontario, Canada

Aarhus Universitetshospital Skejby, Hud- og Kønssygdomme

Aarhus N, , Denmark

Bispebjerg Hospital, Dermatologisk afdeling

København NV, , Denmark

Hopital Claude Huriez; Internal Medicine

Lille, , France

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

Bad Abbach, , Germany

Kerckhoff-Klinik; Rheumatologie&klin.Immunologie

Bad Nauheim, , Germany

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

Dresden, , Germany

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

München, , Germany

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

Tübingen, , Germany

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

Athens, , Greece

University Hospital of Patras; Rheumatology

Pátrai, , Greece

National Institute of Rheumatology and Physiology

Budapest, , Hungary

Pécsi Tudományegyetem Klinikai Központ: Immunológiai és Reumatológiai Klinika

Pécs, , Hungary

Policlinico Universitario-II Università di Napoli; Reumatologia

Napoli, Campania, Italy

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

Rome, Lazio, Italy

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

Milan, Lombardy, Italy

Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia

Florence, Tuscany, Italy

Gunma University Hospital

Gunma, , Japan

Sapporo Medical University Hospital

Hokkaido, , Japan

Hokkaido University Hospital

Hokkaido, , Japan

Kanazawa University Hospital

Ishikawa, , Japan

St. Marianna University School of Medicine Hospital

Kanagawa, , Japan

Hospital of the University of Occupational and Environmental Health,Japan

Kitakyushu-shi, , Japan

Kumamoto University Hospital

Kumamoto, , Japan

Tohoku University Hospital

Miyagi, , Japan

Osaka University Hospital

Osaka, , Japan

Nippon Medical School Hospital

Tokyo, , Japan

The University of Tokyo Hospital

Tokyo, , Japan

Klaipeda University Hospital; Department of Rheumatology

Klaipėda, , Lithuania

Vilnius University Hospital Santariskiu Clinic Public Insti

Vilnius, , Lithuania

Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán

Mexico City, , Mexico

Unidad De Enfermedades; Cronico Degenerativas, SC.

México, , Mexico

Cliditer SA de CV

Miexico City, , Mexico

Academisch Ziekenhuis Leiden; Dept of Rheumatology

Leiden, , Netherlands

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

Bydgoszcz, , Poland

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

Gdansk, , Poland

Gornoslaskie Centrum Medyczne

Katowice, , Poland

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

Krakow, , Poland

SPSK NR 4; Reumatologii i Ukladowych Chorob Tkanki

Lublin, , Poland

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

Warsaw, , Poland

Hospital Garcia de Orta; Servico de Reumatologia

Almada, , Portugal

Hospital Prof. Dr. Fernando Fonseca; Medicina IV

Amadora, , Portugal

Puerto Rico Clinical & Translational Research Consortium

San Juan, , Puerto Rico

Cantacuzino Hospital; Department of Internal Medicine and Rheumatology

Bucharest, , Romania

Spitalul Judetean Cluj; Sectia de Reumatologie

Cluj-Napoca, , Romania

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

Barcelona, , Spain

Hospital Universitario Vall d'Hebron; Servicio de Medicina Interna

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

Madrid, , Spain

Universitätsspital Basel; Rheumatologische Poliklinik

Basel, , Switzerland

Universitätsspital Zürich; Klinik für Rheumatologie

Zurich, , Switzerland

Queen Elizabeth Hospital; Rheumatology Dept.

Birmingham, , United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Chapel Allerton Hospital; Leeds Institution of Rheumatology Medicine

Leeds, , United Kingdom

Uni Hospital Aintree; Academic Rheumatology Unit

Liverpool, , United Kingdom

Royal Free Hospital; Department of Rheumatology

London, , United Kingdom

Freeman Hospital; Musculoskeletal Unit

Newcastle upon Tyne, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 37228011 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34851799 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33538094 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33294861 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32866440 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2015-000424-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA29767

Identifier Type: -

Identifier Source: org_study_id