A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)

NCT00642460 | Completed Phase 3 Results

• 2 other identifiers: WA182212007-000872-18
• Study Type: interventional
• Target: 112
• Locations: 19 countries
• Sites: 54

Brief Summary

This study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active systemic juvenile idiopathic arthritis (sJIA) who have an inadequate clinical response to NSAIDs and corticosteroids. In Part I of the study patients will be randomized 2:1 to receive iv infusions of RoActemra/Actemra (8mg/kg iv for patients \>=30kg, or 12mg/kg for patients \<30kg) or placebo, every 2 weeks. Stable NSAIDs and methotrexate will be continued throughout. After 12 weeks of double-blind treatment, all patients will have the option to enter Part II of the study to receive open-label treatment with RoActemra/Actemra for a further 92 weeks, followed by a 3-year continuation of the study in Part III in which, for patients who meet specific criteria, an optional alternative dosing schedule decreasing the study drug administration frequency will be introduced. Anticipated time on study treatment is up to 5 years.

Conditions

Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (2)

• Part I: Percentage of Participants With ≥30% Improvement in Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) Core Set and Absence of Fever

  Percentage of participants with ≥30% improvement in ACR core set consisting of 6 components: 1) Physician's global assessment of disease activity Visual Analog Scale (VAS), 2) Parent/Patient global assessment of overall well-being VAS, 3) Maximum number of joints with active arthritis, 4) Number of joints with limitation of movement, 5) Erythrocyte Sedimentation Rate, and 6) Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI) consisting of 30 questions in 8 domains. Absence of fever was defined as no diary temperature recording ≥37.5° Celsius in the preceding seven days.

  Baseline, Week 12

• Part II: Percentage of Participants With Decreases in Oral Corticosteroid Dose at Week 104

  Percentage of participants with ≥20 percent, ≥50 percent, ≥75 percent and ≥90 percent decreases in oral corticosteroid dose (mg/kg/day) from baseline.

  Baseline, Week 104

Secondary Outcomes (33)

• Part I: Percentage of Participants With JIA Core Set ACR 30/50/70/90 Response at Week 12

  Baseline, Week 12

• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Physician's Global Assessment of Disease Activity

  Baseline, Week 12

• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Parent/Patient Global Assessment of Overall Well-being

  Baseline, Week 12

• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Maximum Number of Joints With Active Arthritis

  Baseline, Week 12

• Part I: Percentage Change From Baseline in JIA Core Set ACR Score Component: Number of Joints With Limitation of Movement

  Baseline, Week 12

Study Arms (2)

1

EXPERIMENTAL

Drug: tocilizumab [RoActemra/Actemra]; Drug: Non-steroidal anti-inflammatory drugs (NSAIDs); Drug: methotrexate; Drug: corticosteroids

2

PLACEBO COMPARATOR

Drug: Placebo; Drug: Non-steroidal anti-inflammatory drugs (NSAIDs); Drug: methotrexate; Drug: corticosteroids

Interventions

tocilizumab [RoActemra/Actemra] DRUG

8mg/kg (patients\>=30kg) or 12mg/kg (patients \<30kg) iv every 2 weeks. In Part III, administration frequency may be reduced to every 3 and every 4 weeks, respectively, according to an optional alternative dosing schedule.

1

Placebo DRUG

iv every 2 weeks for 12 weeks

2

Non-steroidal anti-inflammatory drugs (NSAIDs) DRUG

as prescribed

1; 2

methotrexate DRUG

as prescribed

1; 2

corticosteroids DRUG

orally, as prescribed

1; 2

Eligibility Criteria

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

You may qualify if:

• Patients aged 2-17 years of age
• Systemic juvenile idiopathic arthritis with \>= 6 months persistent activity
• Presence of active disease (\>=5 active joints, or \>=2 active joints + fever + steroids)
• Inadequate clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids due to toxicity or lack of efficacy

You may not qualify if:

• Wheelchair-bound or bed-ridden
• Any other autoimmune, rheumatic disease or overlap syndrome other than systemic juvenile idiopathic arthritis
• Intravenous long-acting corticosteroids or intra-articular corticosteroids within 4 weeks of baseline, or throughout study
• Disease-modifying antirheumatic drugs (DMARDs), other than methotrexate
• Previous treatment with tocilizumab

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (54)

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Little Rock, Arkansas, 45229-3039, United States

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Los Angeles, California, 90027, United States

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Hartford, Connecticut, 06106, United States

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Augusta, Georgia, 30912, United States

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Chicago, Illinois, United States

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Louisville, Kentucky, 40202-3906, United States

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Hackensack, New Jersey, 07601, United States

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Livingston, New Jersey, 07039, United States

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Durham, North Carolina, 27710, United States

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Cincinnati, Ohio, 45229, United States

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Cleveland, Ohio, 44195, United States

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Oklahoma City, Oklahoma, 73104, United States

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Houston, Texas, 77030, United States

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Buenos Aires, 1270, Argentina

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Buenos Aires, 1425, Argentina

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La Plata, 1900, Argentina

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Parkville, 3052, Australia

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Subiaco, 6008, Australia

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Westmead, 2145, Australia

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Porto Alegre, 90035-903, Brazil

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Rio de Janeiro, 20551-030, Brazil

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São Paulo, 05403-900, Brazil

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Vancouver, British Columbia, V6H 3V4, Canada

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Halifax, Nova Scotia, B3J 3G9, Canada

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Ottawa, Ontario, K1H 8L1, Canada

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Toronto, Ontario, M5G 1X8, Canada

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Prague, 121-09, Czechia

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Copenhagen, 2100, Denmark

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Berlin, 13353, Germany

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Bremen, 28205, Germany

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Sankt Augustin, 53757, Germany

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Athens, 11527, Greece

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Heraklion, 71110, Greece

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Ioannina, 45500, Greece

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Genova, 16147, Italy

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Milan, 20122, Italy

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Padua, 35128, Italy

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Roma, 00165, Italy

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México, 06720, Mexico

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Miexico City, 06700, Mexico

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Utrecht, 3584 AE, Netherlands

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Oslo, 0027, Norway

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Krakow, 31-503, Poland

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Lublin, 20-093, Poland

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Piešťany, 921 01, Slovakia

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Barcelona, 08035, Spain

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Esplugas de Llobregat, 08950, Spain

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Madrid, 28046, Spain

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Valencia, 46026, Spain

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Gothenburg, 41685, Sweden

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Liverpool, L12 2AP, United Kingdom

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London, WC1N IEH, United Kingdom

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Related Publications (4)

• 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

• De Benedetti F, Brunner H, Ruperto N, Schneider R, Xavier R, Allen R, Brown DE, Chaitow J, Pardeo M, Espada G, Gerloni V, Myones BL, Frane JW, Wang J, Lipman TH, Bharucha KN, Martini A, Lovell D; Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group. Catch-up growth during tocilizumab therapy for systemic juvenile idiopathic arthritis: results from a phase III trial. Arthritis Rheumatol. 2015 Mar;67(3):840-8. doi: 10.1002/art.38984.

  PMID: 25504861 DERIVED

• De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A; PRINTO; PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012 Dec 20;367(25):2385-95. doi: 10.1056/NEJMoa1112802.

  PMID: 23252525 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

tocilizumab; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

This study consists of 3 parts: Part I: a 12 week double-blind placebo controlled study is complete. Part II: a 92 week single arm open-label extension study- CSR completed Dec. 2011. Part III: a 3 year open label continuation study is ongoing.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2008
• First Posted: March 25, 2008
• Study Start: May 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: August 1, 2014
• Last Updated: July 25, 2016
• Results First Posted: October 26, 2011

Record last verified: 2016-06

Locations

GB (2); US (13); DE (3); IT (4); NL (1); CZ (1); ME (2); AR (3); BE (2); ES (4); BR (3); NO (1); GR (3); AU (3); SL (1); CA (4); DK (1); SE (1); PL (2)