Back to resultsA Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
Primary Purpose
Juvenile Idiopathic Arthritis
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Juvenile Idiopathic Arthritis
Eligibility Criteria
Inclusion Criteria:
PART 1 and 2
- Children 2 to 17 years of age inclusive at screening
- Systemic juvenile idiopathic arthritis (sJIA) according to International League of Associations for Rheumatology (ILAR) classification (2001) and sJIA symptoms lasting for at least 1 month since diagnosis of sJIA
- Must meet one of the following:
- Not receiving methotrexate (MTX) or discontinued MTX at least 4 weeks prior to baseline visit, or
- Taking MTX for at least 12 weeks immediately prior to the baseline visit and on a stable dose of less than or equals (</=) 20 milligrams per meter square (mg/m^2) for at least 8 weeks prior to the baseline visit, together with either folic acid or folinic acid according to local standard of care
- Participants entering Part 1 who are naive to TCZ therapy must also meet the following inclusion criterion:
- History of inadequate clinical response (in the opinion of the treating physician) to Non steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids PART 2
- Juvenile Arthritis Disease Activity Score (JADAS) -71 score of 3.8 or less and absence of fever (related to sJIA) at screening and baseline
- Neutropenia, thrombocytopenia, or elevated Alanine transaminase/Aspartate transaminase (ALT/AST) previously experienced on the labeled dose (Q2W) of RoActemra/Actemra at any time
- Not currently receiving oral corticosteroids, or taking oral corticosteroids at a stable dose for a minimum of 2 weeks prior to baseline visit at no more than 10 milligrams per day (mg/day) or 0.2 miiligrams per kilogram per day (mg/kg/day), whichever is less
- Not taking (NSAIDs), or taking no more than 1 type of NSAID at a stable dose for a minimum of 2 weeks prior to the baseline visit, with the dose being less than or equal to the maximum recommended daily dose
Exclusion Criteria:
- Wheelchair bound or bedridden
- Any other auto-immune, rheumatic disease, or overlap syndrome other than sJIA
- Pregnant or lactating, or intending to become pregnant during study conduct and up to 6 months after the last administration of study drug
- Any significant concurrent medical or surgical condition which would jeopardize the participant's safety or ability to complete the trial
- History of significant allergic or infusion reactions to prior TCZ infusion, and/or presence of anti-TCZ antibodies at screening
- Inborn conditions characterized by a compromised immune system
- Known Human Immunodeficiency Virus (HIV) infection or other acquired forms of immune compromise
- History of alcohol, drug, or chemical abuse within 6 months of screening
- Evidence of serious uncontrolled concomitant diseases, including but not limited to the nervous, renal, hepatic, or endocrine systems
- Any active acute, subacute, chronic or recurrent bacterial, viral, or systemic fungal infection
- History of atypical tuberculosis (TB)
- Active TB requiring treatment within 2 years prior to the screening visit
- Positive purified protein derivative (PPD) at screening
- Any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completing within 4 weeks of the screening visit or oral antibiotics completing within 2 weeks of the screening visit
- History of reactivation or new onset of a systemic infection within 2 months of the screening visit
- Positive for hepatitis B or hepatitis C infection
- Chronic hepatitis, viral or pulmonary disease
- Significant cardiac or pulmonary disease
- History of or current cancer or lymphoma
- Uncontrolled diabetes mellitus
- History of or concurrent serious gastrointestinal disorders
- History of macrophage activation syndrome (MAS) within 3 months prior to screening visit
Sites / Locations
- Children's Hospital Los Angeles; Division of Rheumatoogy
- Cincinnati Children'S Hospital Medical Center; Division of Rheumatology
- Hospital Gral de Niños Pedro Elizalde
- Hospital Dr. Humberto Notti
- Alberta Children'S Hospital
- Charité Campus; Virchow Klinikum Berlin
- Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie
- Rambam Medicl Center, Ruth Children Hospital
- Meir Medical center, Pediatrics
- Schneider Children's Medical Center of Israel
- Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina
- Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica
- Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
- SI Sceintific children health center RAMS
- Saint-Petersburg State; Pediatrics Medical Academy
- Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica
- Hospital Ramon y Cajal ; Servicio de Reumatologia
- Hospital de La Paz; Unidad de Reumatologia Pediatrica
- Royal Liverpool Childrens Hospital; Rheumatology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1: Tocilizumab (TCZ) Q2W
Part 2: TCZ IV 12 mg/kg Q3W/Q4W
Part 2: TCZ IV 8 mg/kg Q3W/Q4W
Arm Description
Participants will receive tocilizumab intravenous (IV) infusions (12 mg/kg for participants < 30 kg; 8 mg/kg for participants >/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.
Participants with weight < 30 kg will receive tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.
Participants with weight >/= 30 kg will receive tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Outcomes
Primary Outcome Measures
Juvenile Arthritis Disease Activity Score (JADAS-71)
JADAS-71 has 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range=0-10, left end of line=arthritis inactive, i.e., symptom-free and no arthritis symptoms; right end=arthritis very active), patient/parent global assessment of overall well-being on VAS (range=0-10, left end of line=very well, right end=very poor), normalized erythrocyte sedimentation rate (ESR) (range=0-10, If ESR is ≤20 mm/h, set to 0. If ≥120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR-20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). JADAS-71 is sum of 4 component scores, range=0-101. A higher score=more arthritis disease activity. Data reported for up to Week 52 was collected in Part 2: Q3W arms: Baseline, Weeks 3,6,9,12,24,36,48 and 51; Q4W arms: Baseline, Weeks 0,4,8,12,24,36 and 40.
Number of Participants With Juvenile Idiopathic Arthritis (JIA) Disease Flare as Determined by JIA Core Variables in Part 2 of the Study
JIA flare was defined as any 3 of the 6 core outcome variables worsening by at least 30% relative to baseline visit of Part 2, with no more than 1 of the remaining variables improving by more than 30%. For the number of joints with active arthritis or the number of joints with limitation of motion a minimum worsening of at least 2 joints had to be present. If the physician global assessment (PGA) or the parent/patient global assessment were used a minimum worsening of at least 2 units on a scale from 0 to 10 had be present. For erythrocyte sedimentation rate (ESR), a worsening of at least 30% was not considered if within normal ranges. The 6 core outcome variables: PGA of disease activity, parent/patient global assessment of overall well-being, number of joints with active arthritis, number of joints with limitation of movement, ESR (measure of acute phase reaction) and functional ability determined by Childhood Health Assessment Questionnaire (CHAQ) Disability Index.
Number of Participants With Fever Attributable to Systemic Juvenile Idiopathic Arthritis (sJIA) in Part 2 of the Study
Absence of fever at screening visit was defined as a temperature measurement < 38 degree centigrades (C). Presence of fever at each study visit was defined as a temperature measurement ≥ 38 C.
Secondary Outcome Measures
Number of Participants With at Least One Adverse Event
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study
C-reactive Protein (CRP) Concentration in Part 2 of the Study
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study
Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study
Serum TCZ Concentration in Part 2 of the Study
Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability.
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability. Negative change from baseline indicates an improvement.
Baseline Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
Participant's/parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity).
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
Participant's/Parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity). Reported is the change from baseline in VAS score with a negative change from baseline indicating an improvement.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01734382
Brief Title
A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
Official Title
A Phase IV Study to Evaluate Decreased Dose Frequency in Patients With Systemic Juvenile Arthritis (SJIA) Who Experience Laboratory Abnormalities During Treatment With Tocilizumab
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
June 10, 2013 (Actual)
Primary Completion Date
October 9, 2019 (Actual)
Study Completion Date
October 9, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
PART1 Participants in Part 1 (Run-in-Phase) of study will receive tocilizumab (TCZ) (RoActemra/Actemra) 12 milligrams per kilogram (mg/kg) or 8 mg/kg intravenously (IV) every 2 weeks (Q2W) for up to 24 weeks. Participants who experience a laboratory abnormality during Part 1 may be eligible to move into Part 2 of the study.
PART 2 This open-label Phase IV study will evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of tocilizumab in reduced dose frequency in participants with adequately controlled systemic juvenile idiopathic arthritis who have experienced a laboratory abnormality on twice weekly tocilizumab dosing, that has since resolved. Participants will receive tocilizumab 12 mg/kg or 8 mg/kg intravenously every 3 weeks. After 5 consecutive infusions, participants who experience an event of neutropenia, thrombocytopenia or liver enzyme abnormality will move to every 4 weeks tocilizumab administration. Anticipated time on study treatment is 52 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Tocilizumab (TCZ) Q2W
Arm Type
Experimental
Arm Description
Participants will receive tocilizumab intravenous (IV) infusions (12 mg/kg for participants < 30 kg; 8 mg/kg for participants >/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.
Arm Title
Part 2: TCZ IV 12 mg/kg Q3W/Q4W
Arm Type
Experimental
Arm Description
Participants with weight < 30 kg will receive tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.
Arm Title
Part 2: TCZ IV 8 mg/kg Q3W/Q4W
Arm Type
Experimental
Arm Description
Participants with weight >/= 30 kg will receive tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra/Actemra
Intervention Description
Participants will receive tocilizumab IV infusions of 12 mg/kg (for participants < 30 kg) or 8 mg/kg (for participants >/=30 kg) Q2W/Q3W/Q4W.
Primary Outcome Measure Information:
Title
Juvenile Arthritis Disease Activity Score (JADAS-71)
Description
JADAS-71 has 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range=0-10, left end of line=arthritis inactive, i.e., symptom-free and no arthritis symptoms; right end=arthritis very active), patient/parent global assessment of overall well-being on VAS (range=0-10, left end of line=very well, right end=very poor), normalized erythrocyte sedimentation rate (ESR) (range=0-10, If ESR is ≤20 mm/h, set to 0. If ≥120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR-20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). JADAS-71 is sum of 4 component scores, range=0-101. A higher score=more arthritis disease activity. Data reported for up to Week 52 was collected in Part 2: Q3W arms: Baseline, Weeks 3,6,9,12,24,36,48 and 51; Q4W arms: Baseline, Weeks 0,4,8,12,24,36 and 40.
Time Frame
Part 2: Up to 52 weeks
Title
Number of Participants With Juvenile Idiopathic Arthritis (JIA) Disease Flare as Determined by JIA Core Variables in Part 2 of the Study
Description
JIA flare was defined as any 3 of the 6 core outcome variables worsening by at least 30% relative to baseline visit of Part 2, with no more than 1 of the remaining variables improving by more than 30%. For the number of joints with active arthritis or the number of joints with limitation of motion a minimum worsening of at least 2 joints had to be present. If the physician global assessment (PGA) or the parent/patient global assessment were used a minimum worsening of at least 2 units on a scale from 0 to 10 had be present. For erythrocyte sedimentation rate (ESR), a worsening of at least 30% was not considered if within normal ranges. The 6 core outcome variables: PGA of disease activity, parent/patient global assessment of overall well-being, number of joints with active arthritis, number of joints with limitation of movement, ESR (measure of acute phase reaction) and functional ability determined by Childhood Health Assessment Questionnaire (CHAQ) Disability Index.
Time Frame
Part 2: Up to 52 weeks
Title
Number of Participants With Fever Attributable to Systemic Juvenile Idiopathic Arthritis (sJIA) in Part 2 of the Study
Description
Absence of fever at screening visit was defined as a temperature measurement < 38 degree centigrades (C). Presence of fever at each study visit was defined as a temperature measurement ≥ 38 C.
Time Frame
Part 2: Up to 52 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With at Least One Adverse Event
Description
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
Part 1 - Baseline up to 24 weeks plus 12 weeks of safety follow up; Part 2 - Baseline up to 52 weeks plus 12 weeks of safety follow up
Title
Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study
Time Frame
Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40
Title
Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study
Time Frame
Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40
Title
C-reactive Protein (CRP) Concentration in Part 2 of the Study
Time Frame
Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40
Title
Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study
Time Frame
Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40
Title
Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study
Time Frame
Part 2: Up to Week 52
Title
Serum TCZ Concentration in Part 2 of the Study
Time Frame
Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40
Title
Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
Description
CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability.
Time Frame
Baseline of Part 2
Title
Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
Description
CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability. Negative change from baseline indicates an improvement.
Time Frame
Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40
Title
Baseline Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
Description
Participant's/parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity).
Time Frame
Baseline of Part 2
Title
Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
Description
Participant's/Parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity). Reported is the change from baseline in VAS score with a negative change from baseline indicating an improvement.
Time Frame
Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
PART 1 and 2
Children 2 to 17 years of age inclusive at screening
Systemic juvenile idiopathic arthritis (sJIA) according to International League of Associations for Rheumatology (ILAR) classification (2001) and sJIA symptoms lasting for at least 1 month since diagnosis of sJIA
Must meet one of the following:
Not receiving methotrexate (MTX) or discontinued MTX at least 4 weeks prior to baseline visit, or
Taking MTX for at least 12 weeks immediately prior to the baseline visit and on a stable dose of less than or equals (</=) 20 milligrams per meter square (mg/m^2) for at least 8 weeks prior to the baseline visit, together with either folic acid or folinic acid according to local standard of care
Participants entering Part 1 who are naive to TCZ therapy must also meet the following inclusion criterion:
History of inadequate clinical response (in the opinion of the treating physician) to Non steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids PART 2
Juvenile Arthritis Disease Activity Score (JADAS) -71 score of 3.8 or less and absence of fever (related to sJIA) at screening and baseline
Neutropenia, thrombocytopenia, or elevated Alanine transaminase/Aspartate transaminase (ALT/AST) previously experienced on the labeled dose (Q2W) of RoActemra/Actemra at any time
Not currently receiving oral corticosteroids, or taking oral corticosteroids at a stable dose for a minimum of 2 weeks prior to baseline visit at no more than 10 milligrams per day (mg/day) or 0.2 miiligrams per kilogram per day (mg/kg/day), whichever is less
Not taking (NSAIDs), or taking no more than 1 type of NSAID at a stable dose for a minimum of 2 weeks prior to the baseline visit, with the dose being less than or equal to the maximum recommended daily dose
Exclusion Criteria:
Wheelchair bound or bedridden
Any other auto-immune, rheumatic disease, or overlap syndrome other than sJIA
Pregnant or lactating, or intending to become pregnant during study conduct and up to 6 months after the last administration of study drug
Any significant concurrent medical or surgical condition which would jeopardize the participant's safety or ability to complete the trial
History of significant allergic or infusion reactions to prior TCZ infusion, and/or presence of anti-TCZ antibodies at screening
Inborn conditions characterized by a compromised immune system
Known Human Immunodeficiency Virus (HIV) infection or other acquired forms of immune compromise
History of alcohol, drug, or chemical abuse within 6 months of screening
Evidence of serious uncontrolled concomitant diseases, including but not limited to the nervous, renal, hepatic, or endocrine systems
Any active acute, subacute, chronic or recurrent bacterial, viral, or systemic fungal infection
History of atypical tuberculosis (TB)
Active TB requiring treatment within 2 years prior to the screening visit
Positive purified protein derivative (PPD) at screening
Any major episode of infection requiring hospitalization or treatment during screening or treatment with IV antibiotics completing within 4 weeks of the screening visit or oral antibiotics completing within 2 weeks of the screening visit
History of reactivation or new onset of a systemic infection within 2 months of the screening visit
Positive for hepatitis B or hepatitis C infection
Chronic hepatitis, viral or pulmonary disease
Significant cardiac or pulmonary disease
History of or current cancer or lymphoma
Uncontrolled diabetes mellitus
History of or concurrent serious gastrointestinal disorders
History of macrophage activation syndrome (MAS) within 3 months prior to screening visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Los Angeles; Division of Rheumatoogy
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Cincinnati Children'S Hospital Medical Center; Division of Rheumatology
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Hospital Gral de Niños Pedro Elizalde
City
Buenos Aires
ZIP/Postal Code
1270
Country
Argentina
Facility Name
Hospital Dr. Humberto Notti
City
Mendoza
ZIP/Postal Code
5519
Country
Argentina
Facility Name
Alberta Children'S Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Charité Campus; Virchow Klinikum Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie
City
Sankt Augustin
ZIP/Postal Code
53757
Country
Germany
Facility Name
Rambam Medicl Center, Ruth Children Hospital
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Meir Medical center, Pediatrics
City
Kfar Sava
ZIP/Postal Code
4428164
Country
Israel
Facility Name
Schneider Children's Medical Center of Israel
City
Petach Tikva
ZIP/Postal Code
4920235
Country
Israel
Facility Name
Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina
City
Roma
State/Province
Lazio
ZIP/Postal Code
00165
Country
Italy
Facility Name
Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
City
Mexicali
ZIP/Postal Code
21100
Country
Mexico
Facility Name
SI Sceintific children health center RAMS
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
Saint-Petersburg State; Pediatrics Medical Academy
City
Saint-Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Ramon y Cajal ; Servicio de Reumatologia
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital de La Paz; Unidad de Reumatologia Pediatrica
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Royal Liverpool Childrens Hospital; Rheumatology
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
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