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

NCT00988221 | Completed Phase 3 Results

• 2 other identifiers: WA199772009-011593-15
• Study Type: interventional
• Target: 188
• Locations: 15 countries
• Sites: 69

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

Outcome Measures

Primary Outcomes (1)

• Percent of Patients With a Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30 (ACR30) Flare in Part II of the Study (Weeks 16-40)

  JIA ACR30 flare is defined as a ≥ 30% worsening of 3 of 6 variables and no more than 1 of the remaining variables improving \> 30%. The 6 variables are physician global assessment of disease activity (worsening of 20 units minimum on a 0-100 visual analog scale \[VAS\]), parent/patient global assessment of overall well-being (worsening of 20 VAS units minimum), number of joints (minimum of 2 worse) with active arthritis (swelling, or pain and limitation of motion), number of joints (minimum of 2 worse) with limitation of movement, erythrocyte sedimentation rate, and functional ability assessed using the disability index of the Childhood Health Assessment Questionnaire (CHAQ, 30 questions, 8 domains, 0\[best\]-3\[worst\]). Patients who withdrew or who took escape medication are classified as flared. The analysis used the Cochran-Mantel-Haenszel test with the stratification variables background use of methotrexate and oral corticosteroids applied at Week 16.

  Week 16 through Week 40

Secondary Outcomes (41)

• Percent of Patients Achieving Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology 30, 50, 70, and 90 (ACR30/50/70/90) Responses in Part I of the Study (Baseline to Week 16)

  Baseline to Week 16

• Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Physician Global Assessment of Disease Activity at the End of Part I of the Study (Week 16)

  Baseline to Week 16

• Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Patient/Parent Global Assessment of Overall Well-being at the End of Part I of the Study (Week 16)

  Baseline to Week 16

• Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Active Arthritis at the End of Part I of the Study (Week 16)

  Baseline to Week 16

• Percent Change From Baseline in the Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Component Score Number of Joints With Limitation of Movement at the End of Part I of the Study (Week 16)

  Baseline to Week 16

Study Arms (4)

Tocilizumab 10 mg/kg in patients weighing < 30 kg

EXPERIMENTAL

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

Drug: Tocilizumab

Tocilizumab 8 mg/kg in patients weighing < 30 kg

EXPERIMENTAL

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

Drug: Tocilizumab

Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg

EXPERIMENTAL

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

Drug: Tocilizumab

Placebo

PLACEBO COMPARATOR

Patients received placebo to tocilizumab intravenously every 4 weeks.

Drug: Placebo

Interventions

Tocilizumab DRUG

Tocilizumab was supplied as a sterile solution in vials.

Also known as: RoActemra, Actemra

Tocilizumab 10 mg/kg in patients weighing < 30 kg; Tocilizumab 8 mg/kg in patients weighing < 30 kg; Tocilizumab 8 mg/kg in patients weighing ≥ 30 kg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (69)

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

Hartford, Connecticut, 06106, United States

Location

Children's National Medical Center; Pediatric Rheumatology

Washington D.C., District of Columbia, 20010-2970, United States

Location

Delray Research Associates

Delray Beach, Florida, 33484, United States

Location

Miami Children's Hospital

Miami, Florida, 33155-3009, United States

Location

The University of Chicago;Department of Pediatrics

Chicago, Illinois, 60649, United States

Location

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

Louisville, Kentucky, 40202, United States

Location

Children's Hospital

New Orleans, Louisiana, 70118, United States

Location

Hackensack University Medical Center; Pediatric Rheumatology

Hackensack, New Jersey, 07601, United States

Location

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, 45229-3039, United States

Location

Healthcare Research Consultants

Tulsa, Oklahoma, 74135, United States

Location

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, 1270, Argentina

Location

Hospital de Niños; Reumatologia

Buenos Aires, 1425, Argentina

Location

Caici; Rheumatology

Rosario, S2000PBJ, Argentina

Location

Centro Medico Privado de Reumatologia; Reumathology

San Miguel, T4000AXL, Argentina

Location

Westmead Hospital; Paediatric Rheumatology

Westmead, New South Wales, 2145, Australia

Location

Royal Children'S Hospital; Paediatric Rheumatology

Parkville, Victoria, 3052, Australia

Location

Princess Margaret Children'S Hospital; Department of Immunology

Subiaco, Western Australia, 6008, Australia

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

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

Rio de Janeiro, Rio de Janeiro, 20551030, Brazil

Location

Instituto de Puericultura E Pediatria Martagão Gesteira

Rio de Janeiro, Rio de Janeiro, 21941-912, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Hospital das Clinicas - FMUSP; Instituto da Crianca - Reumatologia

São Paulo, São Paulo, 05403-000, Brazil

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital; Rheumatology

Vancouver, British Columbia, V5Y 2C6, Canada

Location

Children'S Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Pellegrin; Urgences Pédiatriques

Bordeaux, 33076, France

Location

CH de Bicêtre; Pediatrie Generale

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital Lapeyronie; Immuno-Rhumatologie Pr Jorgensen

Montpellier, 34295, France

Location

Hopital Cochin; Rhumatologie A

Paris, 75679, France

Location

Hop Necker Enfants Malades;UIH

Paris, 75743, France

Location

Hopitaux De Brabois; Medecine Infantile II

Vandœuvre-lès-Nancy, 54511, France

Location

Charité Campus; Virchow Klinikum Berlin

Berlin, 13353, Germany

Location

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

Bremen, 28177, Germany

Location

Clementine Hospital; Kinder- und Jugendrheumatologie

Frankfurt am Main, 60316, Germany

Location

Asklepios Klinik; Zentrum fuer Allgemeine Paediatrie und Neonatologie

Sankt Augustin, 53757, Germany

Location

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, 00165, Italy

Location

IRCCS G. Gaslini; Pediatria II

Genoa, Liguria, 16147, Italy

Location

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

Milan, Lombardy, 20122, Italy

Location

Nuovo Ospedale Pediatrico Meyer; Reumatologia - Clinica Pediatrica 1°

Florence, Tuscany, 50139, Italy

Location

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

Padua, Veneto, 35128, Italy

Location

Inst. Mexicano de Investigacion Clinica

Mexico City, 06700, Mexico

Location

Cif Biotec Medica Sur

Mexico City, Distrito Federal, 14050, Mexico

Location

Cliditer SA de CV

Miexico City, 06700, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria

Monterrey, 64460, Mexico

Location

Clinica San Felipe; Consultorio de Reumatología

Lima, 11, Peru

Location

Clinica San Borja; Servicio De Reumatologia

Lima, Lima 41, Peru

Location

Instituto Nacional De Salud Del Niño

Lima, Peru

Location

Wojewodzki Szpital Dzieciecy Im. J. Brudzinskiego

Bydgoszcz, 85-667, Poland

Location

Wojewodzki Specjalistyczny Szpital Dzieciecy Sw Ludwika; Oddzial Dzieci Starszych

Krakow, 31-503, Poland

Location

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

Lodz, 91-738, Poland

Location

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

Lublin, 20-093, Poland

Location

Centrum Pediatrii im Jana Pawla II; Oddzial Reumatologiczny

Sosnowiec, 41-218, Poland

Location

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

Warsaw, 02-637, Poland

Location

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

Moscow, 115522, Russia

Location

SI Sceintific children health center RAMS

Moscow, 119991, Russia

Location

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

Moscow, 119992, Russia

Location

Southern District Medical Center of Roszdrav

Rostov-on-Don, 344019, Russia

Location

Saint-Petersburg State; Pediatrics Medical Academy

Saint Petersburg, 194100, Russia

Location

Samara Regional Clinical Cardiology Dispensary

Samara, 443070, Russia

Location

Hospital Universitario Reina Sofia; Servicio de Reumatologia

Córdoba, 14004, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Reumatología

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal ; Servicio de Reumatologia

Madrid, 28034, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Reumatologia

Seville, 41009, Spain

Location

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, 46026, Spain

Location

Bristol Royal Hospital For Children

Bristol, BS2 8BJ, United Kingdom

Location

Royal Liverpool Childrens Hospital; Rheumatology

Liverpool, L12 2AP, United Kingdom

Location

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

London, WC1N IEH, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 36651601 DERIVED

• 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.

  PMID: 32912276 DERIVED

• 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.

  PMID: 30824645 DERIVED

• 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.

  PMID: 24834925 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

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

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: October 1, 2009
• First Posted: October 2, 2009
• Study Start: November 30, 2009
• Primary Completion: November 30, 2011
• Study Completion: January 28, 2013
• Last Updated: July 26, 2017
• Results First Posted: November 1, 2012

Record last verified: 2017-06

Locations

GB (3); BE (2); BR (4); CA (4); AU (3); IT (5); ME (4); DE (4); FR (6); AR (4); ES (5); PE (3); US (10); PL (6); RU (6)