A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

NCT ID: NCT00988221

Last Updated: 2017-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2013-01-28

Brief Summary

This 3-part study evaluated the efficacy and safety of tocilizumab in patients with active polyarticular-course juvenile idiopathic arthritis who have an inadequate response to, or were intolerant of methotrexate. In Part I of the study, all patients received intravenous (iv) infusions of tocilizumab (8 mg/kg for patients ≥ 30kg, 8 mg/kg or 10 mg/kg for patients < 30kg) every 4 weeks for 16 weeks. In Part II of the study, patients with an adequate response in Part I were randomized to receive either tocilizumab at the same dose as in Part I or placebo every 4 weeks for up to 24 weeks. In Part III of the study, patients received tocilizumab at the same dose as in Part I every 4 weeks for up to another 64 weeks. Standard of care therapy with or without non-steroidal anti-inflammatory drugs (NSAID), corticosteroids, or methotrexate was continued throughout the study.

Conditions

Juvenile Idiopathic Arthritis

Study Design

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

Study Groups

Tocilizumab 10 mg/kg in patients weighing < 30 kg

Patients received tocilizumab 10 mg/kg intravenously every 4 weeks.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab was supplied as a sterile solution in vials.

Tocilizumab 8 mg/kg in patients weighing < 30 kg

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab was supplied as a sterile solution in vials.

Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab was supplied as a sterile solution in vials.

Placebo

Patients received placebo to tocilizumab intravenously every 4 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to tocilizumab was supplied as a sterile solution in vials.

Interventions

Tocilizumab

Tocilizumab was supplied as a sterile solution in vials.

Intervention Type: DRUG

Placebo

Placebo to tocilizumab was supplied as a sterile solution in vials.

Intervention Type: DRUG

Other Intervention Names

RoActemra; Actemra

Eligibility Criteria

Inclusion Criteria

• Children/juveniles, 2-17 years of age.
• Polyarticular-course juvenile idiopathic arthritis (pcJIA) ≥ 6 months duration.
• Active disease (≥ 5 active joints, ≥ 3 with limitation of motion).
• Inadequate response to or inability to tolerate methotrexate.
• Methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAID) at stable dose(at least 8, 4, and 2 weeks,respectively) prior to baseline.
• Biologics discontinued, between at least 1 and 20 weeks prior to baseline, depending on biologic.

Exclusion Criteria

• Auto-immune, rheumatic disease or overlap syndrome other than pcJIA.
• Wheelchair bound or bedridden.
• Intra-articular, intramuscular, intravenous, or long-acting corticosteroids within 4 weeks prior to baseline.
• Disease-modifying anti-rheumatic drugs (DMARD) (other than methotrexate) within 4 weeks prior to baseline.
• Previous treatment with tocilizumab.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 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

Connecticut Children's Medical Center; 5E Clinical Trials Unit

Hartford, Connecticut, United States

Children's National Medical Center; Pediatric Rheumatology

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

Delray Research Associates

Delray Beach, Florida, United States

Miami Children's Hospital

Miami, Florida, United States

The University of Chicago;Department of Pediatrics

Chicago, Illinois, United States

University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Children's Hospital

New Orleans, Louisiana, United States

Hackensack University Medical Center; Pediatric Rheumatology

Hackensack, New Jersey, United States

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, United States

Healthcare Research Consultants

Tulsa, Oklahoma, United States

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, , Argentina

Hospital de Niños; Reumatologia

Buenos Aires, , Argentina

Caici; Rheumatology

Rosario, , Argentina

Centro Medico Privado de Reumatologia; Reumathology

San Miguel, , Argentina

Westmead Hospital; Paediatric Rheumatology

Westmead, New South Wales, Australia

Royal Children'S Hospital; Paediatric Rheumatology

Parkville, Victoria, Australia

Princess Margaret Children'S Hospital; Department of Immunology

Subiaco, Western Australia, Australia

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Hospital Universitario Pedro Ernesto; Nucleo de Estudos da Saude do Adolescente

Rio de Janeiro, Rio de Janeiro, Brazil

Instituto de Puericultura E Pediatria Martagão Gesteira

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, Brazil

Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia

São Paulo, São Paulo, Brazil

Alberta Children'S Hospital

Calgary, Alberta, Canada

British Columbia Children's Hospital; Rheumatology

Vancouver, British Columbia, Canada

Children'S Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Hospital For Sick Children

Toronto, Ontario, Canada

Hôpital Pellegrin; Urgences Pédiatriques

Bordeaux, , France

CH de Bicêtre; Pediatrie Generale

Le Kremlin-Bicêtre, , France

Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen

Montpellier, , France

Hopital Cochin; Rhumatologie A

Paris, , France

Hop Necker Enfants Malades;UIH

Paris, , France

Hopitaux De Brabois; Medecine Infantile II

Vandœuvre-lès-Nancy, , France

Charité Campus; Virchow Klinikum Berlin

Berlin, , Germany

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

Bremen, , Germany

Clementine Hospital; Kinder- und Jugendrheumatologie

Frankfurt am Main, , Germany

Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie

Sankt Augustin, , Germany

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, Italy

IRCCS G. Gaslini; Pediatria II

Genoa, Liguria, Italy

ASST CENTRO SPECIALISTICO ORTOPEDICO TRAUMATO-LOGICO GAETANO PINI/CTO; Reumatol. Pediatrica

Milan, Lombardy, Italy

Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°

Florence, Tuscany, Italy

Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

Padua, Veneto, Italy

Inst. Mexicano de Investigacion Clinica

Mexico City, , Mexico

Cif Biotec Medica Sur

Mexico City, Distrito Federal, , Mexico

Cliditer SA de CV

Miexico City, , Mexico

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

Monterrey, , Mexico

Clinica San Felipe; Consultorio de Reumatología

Lima, , Peru

Clinica San Borja; Servicio De Reumatologia

Lima, , Peru

Instituto Nacional De Salud Del Niño

Lima, , Peru

Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego

Bydgoszcz, , Poland

Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych

Krakow, , Poland

Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci

Lodz, , Poland

Dzieciecy Szpital Kliniczny IM. Prof. A. Gebali; Oddzial Pediatrii Chorob Pluc I Reumatologii

Lublin, , Poland

Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny

Sosnowiec, , Poland

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

Warsaw, , Poland

FSBI "Scientific Research Institute of Rheumatology" of russian Academy of Medical Sciences

Moscow, , Russia

SI Sceintific children health center RAMS

Moscow, , Russia

I. M. Sechenov Moscow State Medical University; The Ministry of Health and Social Development of RF

Moscow, , Russia

Southern District Medical Center of Roszdrav

Rostov-on-Don, , Russia

Saint-Petersburg State; Pediatrics Medical Academy

Saint Petersburg, , Russia

Samara Regional Clinical Cardiology Dispensary

Samara, , Russia

Hospital Universitario Reina Sofia; Servicio de Reumatologia

Córdoba, , Spain

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

Madrid, , Spain

Hospital Ramon y Cajal ; Servicio de Reumatologia

Madrid, , Spain

Hospital Universitario Virgen Macarena; Servicio de Reumatologia

Seville, , Spain

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, , Spain

Bristol Royal Hospital For Children

Bristol, , United Kingdom

Royal Liverpool Childrens Hospital; Rheumatology

Liverpool, , United Kingdom

Great Ormond Street Hospital for Sick Children; Institute of Child Health

London, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; France; Germany; Italy; Mexico; Peru; Poland; Russia; Spain; United Kingdom

References

Lim LSH, Lokku A, Pullenayegum E, Ringold S. Probability of Response in the First Sixteen Weeks After Starting Biologics: An Analysis of Juvenile Idiopathic Arthritis Biologics Trials. Arthritis Care Res (Hoboken). 2023 Jun;75(6):1238-1249. doi: 10.1002/acr.25003. Epub 2023 Jan 18.

Reference Type: DERIVED

PMID: 36651601 (View on PubMed)

Malattia C, Ruperto N, Pederzoli S, Palmisani E, Pistorio A, Wouters C, Dolezalova P, Flato B, Garay S, Giancane G, Wells C, Douglass W, Brunner HI, De Benedetti F, Ravelli A; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials. Arthritis Res Ther. 2020 Sep 10;22(1):211. doi: 10.1186/s13075-020-02303-y.

Reference Type: DERIVED

PMID: 32912276 (View on PubMed)

Pardeo M, Wang J, Ruperto N, Alexeeva E, Chasnyk V, Schneider R, Horneff G, Huppertz HI, Minden K, Onel K, Zemel L, Martin A, Kone-Paut I, Siamopoulou-Mavridou A, Silva CA, Porter-Brown B, Bharucha KN, Brunner HI, De Benedetti F; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Neutropenia During Tocilizumab Treatment Is Not Associated with Infection Risk in Systemic or Polyarticular-course Juvenile Idiopathic Arthritis. J Rheumatol. 2019 Sep;46(9):1117-1126. doi: 10.3899/jrheum.180795. Epub 2019 Mar 1.

Reference Type: DERIVED

PMID: 30824645 (View on PubMed)

Brunner HI, Ruperto N, Zuber Z, Keane C, Harari O, Kenwright A, Lu P, Cuttica R, Keltsev V, Xavier RM, Calvo I, Nikishina I, Rubio-Perez N, Alexeeva E, Chasnyk V, Horneff G, Opoka-Winiarska V, Quartier P, Silva CA, Silverman E, Spindler A, Baildam E, Gamir ML, Martin A, Rietschel C, Siri D, Smolewska E, Lovell D, Martini A, De Benedetti F; Paediatric Rheumatology International Trials Organisation PRINTO; Pediatric Rheumatology Collaborative Study Group (PRCSG). Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015 Jun;74(6):1110-7. doi: 10.1136/annrheumdis-2014-205351. Epub 2014 May 16.

Reference Type: DERIVED

PMID: 24834925 (View on PubMed)

Other Identifiers

2009-011593-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA19977

Identifier Type: -

Identifier Source: org_study_id