A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01734382
Collaborator
(none)
35
19
3
76
1.8
0
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
35 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Jun 10, 2013
Actual Primary Completion Date
:
Oct 9, 2019
Actual Study Completion Date
:
Oct 9, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Tocilizumab (TCZ) Q2W 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. |
Drug: Tocilizumab
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.
Other Names:
|
| Experimental: Part 2: TCZ IV 12 mg/kg Q3W/Q4W 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. |
Drug: Tocilizumab
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.
Other Names:
|
| Experimental: Part 2: TCZ IV 8 mg/kg Q3W/Q4W 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. |
Drug: Tocilizumab
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Juvenile Arthritis Disease Activity Score (JADAS-71) [Part 2: Up to 52 weeks]
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 [Part 2: Up to 52 weeks]
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 [Part 2: Up to 52 weeks]
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 [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]
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 [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]
- Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study [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]
- C-reactive Protein (CRP) Concentration in Part 2 of the Study [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]
- Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study [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]
- Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study [Part 2: Up to Week 52]
- Serum TCZ Concentration in Part 2 of the Study [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]
- Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study [Baseline of Part 2]
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 [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]
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 [Baseline of Part 2]
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 [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]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
2 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital Los Angeles; Division of Rheumatoogy | Los Angeles | California | United States | 90027 |
| 2 | Cincinnati Children'S Hospital Medical Center; Division of Rheumatology | Cincinnati | Ohio | United States | 45229-3039 |
| 3 | Hospital Gral de Niños Pedro Elizalde | Buenos Aires | Argentina | 1270 | |
| 4 | Hospital Dr. Humberto Notti | Mendoza | Argentina | 5519 | |
| 5 | Alberta Children'S Hospital | Calgary | Alberta | Canada | T3B 6A8 |
| 6 | Charité Campus; Virchow Klinikum Berlin | Berlin | Germany | 13353 | |
| 7 | Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie | Sankt Augustin | Germany | 53757 | |
| 8 | Rambam Medicl Center, Ruth Children Hospital | Haifa | Israel | 3109601 | |
| 9 | Meir Medical center, Pediatrics | Kfar Sava | Israel | 4428164 | |
| 10 | Schneider Children's Medical Center of Israel | Petach Tikva | Israel | 4920235 | |
| 11 | Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina | Roma | Lazio | Italy | 00165 |
| 12 | Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica | Padova | Veneto | Italy | 35128 |
| 13 | Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel | Mexicali | Mexico | 21100 | |
| 14 | SI Sceintific children health center RAMS | Moscow | Russian Federation | 119991 | |
| 15 | Saint-Petersburg State; Pediatrics Medical Academy | Saint-Petersburg | Russian Federation | 194100 | |
| 16 | Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica | Barcelona | Spain | 08950 | |
| 17 | Hospital Ramon y Cajal ; Servicio de Reumatologia | Madrid | Spain | 28034 | |
| 18 | Hospital de La Paz; Unidad de Reumatologia Pediatrica | Madrid | Spain | 28046 | |
| 19 | Royal Liverpool Childrens Hospital; Rheumatology | Liverpool | United Kingdom | L12 2AP |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01734382
Other Study ID Numbers:
- WA28029
- 2012-000444-10
First Posted:
Nov 27, 2012
Last Update Posted:
Apr 24, 2020
Last Verified:
Apr 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants with systemic juvenile idiopathic arthritis (sJIA) were recruited at study sites in 8 countries. The study consisted of two parts: Part 1 was a 24-week Run-in period and Part 2 was a 52-week Main study. |
|---|---|
| Pre-assignment Detail | Participants on tocilizumab (TCZ) once every two weeks (Q2W) who had experienced a laboratory abnormality (which resolved) as per protocol criteria either during Part 1 or prior to the study, could enter Part 2. 19 Participants entered Part 1 and 6 continued on to Part 2. 16 participants directly entered Part 2 of the study. |
| Arm/Group Title | Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W |
|---|---|---|---|
| Arm/Group Description | Participants received 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Period Title: Part 1 | |||
| STARTED | 19 | 0 | 0 |
| COMPLETED | 17 | 0 | 0 |
| NOT COMPLETED | 2 | 0 | 0 |
| Period Title: Part 1 | |||
| STARTED | 0 | 7 | 15 |
| COMPLETED | 0 | 5 | 8 |
| NOT COMPLETED | 0 | 2 | 7 |
Baseline Characteristics
| Arm/Group Title | Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. | Total of all reporting groups |
| Overall Participants | 19 | 7 | 15 | 41 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
8.5
(3.6)
|
8.5
(3.6)
|
||
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
6.7
(1.8)
|
11.7
(2.8)
|
10.1
(3.4)
|
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
9
47.4%
|
0
0%
|
0
0%
|
9
22%
|
| Male |
10
52.6%
|
0
0%
|
0
0%
|
10
24.4%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
4
57.1%
|
10
66.7%
|
14
34.1%
|
| Male |
0
0%
|
3
42.9%
|
5
33.3%
|
8
19.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
6
31.6%
|
0
0%
|
0
0%
|
6
14.6%
|
| Not Hispanic or Latino |
13
68.4%
|
0
0%
|
0
0%
|
13
31.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
2
28.6%
|
4
26.7%
|
6
14.6%
|
| Not Hispanic or Latino |
0
0%
|
5
71.4%
|
10
66.7%
|
15
36.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
6.7%
|
1
2.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
1
5.3%
|
0
0%
|
0
0%
|
1
2.4%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
17
89.5%
|
0
0%
|
0
0%
|
17
41.5%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
5.3%
|
0
0%
|
0
0%
|
1
2.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
1
14.3%
|
2
13.3%
|
3
7.3%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
6
85.7%
|
12
80%
|
18
43.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
6.7%
|
1
2.4%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. Number analyzed is the number of participants with data available at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
0.60
(0.839)
|
0.21
(0.247)
|
0.00
(NA)
|
0.35
(0.295)
|
| Week 0 |
0.00
(NA)
|
0.13
(0.242)
|
||
| Week 3 |
1.60
(2.474)
|
0.61
(0.913)
|
||
| Week 4 |
0.00
(NA)
|
0.17
(0.266)
|
||
| Week 6 |
0.54
(0.812)
|
0.39
(0.498)
|
||
| Week 8 |
0.00
(NA)
|
0.20
(0.490)
|
||
| Week 9 |
2.59
(5.402)
|
0.33
(0.420)
|
||
| Week 12 |
0.30
(0.600)
|
0.84
(2.318)
|
0.00
(NA)
|
0.13
(0.327)
|
| Week 24 |
0.42
(0.576)
|
0.05
(0.084)
|
0.00
(NA)
|
0.20
(0.346)
|
| Week 36 |
0.48
(0.950)
|
0.08
(0.150)
|
0.00
(NA)
|
0.00
(0.000)
|
| Week 40 |
0.00
(0.000)
|
|||
| Week 48 |
0.00
(0.000)
|
0.17
(0.289)
|
||
| Week 51 |
0.00
(0.000)
|
0.17
(0.208)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. Number of participants analyzed is the number of participants with data available for analyses. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Count of Participants [Participants] |
1
5.3%
|
3
42.9%
|
0
0%
|
1
2.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of safety. |
| Arm/Group Title | Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W |
|---|---|---|---|
| Arm/Group Description | Participants received 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 19 | 7 | 15 |
| Count of Participants [Participants] |
16
84.2%
|
7
100%
|
14
93.3%
|
| Title | Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
36.340
(19.2413)
|
23.453
(12.1440)
|
51.500
(NA)
|
25.415
(15.0174)
|
| Week 0 |
33.000
(23.3195)
|
|||
| Week 3 |
61.617
(75.5724)
|
22.727
(7.0321)
|
||
| Week 4 |
13.700
(NA)
|
28.364
(24.8937)
|
||
| Week 6 |
46.698
(50.7148)
|
82.995
(216.2854)
|
||
| Week 8 |
14.300
(NA)
|
30.580
(22.0335)
|
||
| Week 9 |
45.231
(46.2539)
|
47.582
(37.2259)
|
||
| Week 12 |
84.100
(57.8972)
|
71.867
(156.4710)
|
11.600
(NA)
|
29.662
(26.0053)
|
| Week 24 |
79.200
(44.8853)
|
23.420
(14.5520)
|
45.000
(NA)
|
29.393
(19.2760)
|
| Week 36 |
67.467
(84.7317)
|
30.025
(16.5470)
|
14.100
(NA)
|
21.500
(15.8392)
|
| Week 40 |
22.820
(24.0133)
|
|||
| Week 48 |
14.533
(1.4154)
|
15.400
(10.0936)
|
||
| Week 51 |
17.523
(9.2077)
|
5.060
(NA)
|
| Title | Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
621.04
(443.779)
|
735.16
(310.983)
|
447.00
(NA)
|
855.00
(325.572)
|
| Week 0 |
72.50
(NA)
|
722.83
(229.530)
|
||
| Week 3 |
632.43
(261.172)
|
707.73
(291.228)
|
||
| Week 4 |
379.00
(NA)
|
653.00
(143.386)
|
||
| Week 6 |
518.67
(272.217)
|
721.73
(253.114)
|
||
| Week 8 |
434.00
(NA)
|
628.50
(145.891)
|
||
| Week 9 |
596.58
(318.685)
|
646.92
(174.932)
|
||
| Week 12 |
656.80
(123.611)
|
666.75
(144.510)
|
411.00
(NA)
|
645.33
(106.952)
|
| Week 24 |
574.54
(347.127)
|
554.33
(124.498)
|
519.00
(NA)
|
546.25
(330.265)
|
| Week 36 |
492.50
(258.445)
|
646.00
(198.499)
|
439.00
(NA)
|
599.75
(122.200)
|
| Week 40 |
609.50
(115.613)
|
|||
| Week 48 |
551.00
(91.000)
|
391.00
(220.293)
|
||
| Week 51 |
651.00
(135.765)
|
517.00
(140.007)
|
| Title | C-reactive Protein (CRP) Concentration in Part 2 of the Study |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacodynamic (PD) population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
4.844
(12.2832)
|
2.309
(6.9847)
|
0.200
(NA)
|
0.958
(1.8575)
|
| Week 0 |
0.610
(NA)
|
0.200
(0.0000)
|
||
| Week 3 |
0.223
(0.0427)
|
0.216
(0.0407)
|
0.200
(NA)
|
0.200
(0.0000)
|
| Week 4 |
0.200
(NA)
|
0.200
(0.0000)
|
||
| Week 6 |
0.291
(0.1499)
|
0.526
(1.0163)
|
||
| Week 8 |
0.200
(NA)
|
0.200
(0.0000)
|
||
| Week 9 |
0.208
(0.0179)
|
0.255
(0.1250)
|
0.200
(NA)
|
0.200
(0.0000)
|
| Week 12 |
0.200
(0.0000)
|
0.238
(0.1201)
|
0.200
(NA)
|
0.203
(0.0082)
|
| Week 24 |
0.280
(0.1789)
|
0.254
(0.1207)
|
0.200
(NA)
|
4.040
(8.5865)
|
| Week 36 |
0.225
(0.0500)
|
0.200
(0.0000)
|
0.200
(NA)
|
0.200
(0.0000)
|
| Week 40 |
0.200
(0.0000)
|
|||
| Week 48 |
0.200
(0.0000)
|
0.820
(1.0739)
|
||
| Week 51 |
0.318
(0.2350)
|
0.200
(0.0000)
|
| Title | Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PD population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of PD. Number analyzed is the number of participants with data available at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
3.43
(5.192)
|
3.00
(1.852)
|
1.00
(NA)
|
3.17
(1.602)
|
| Week 0 |
4.00
(NA)
|
2.67
(1.633)
|
||
| Week 3 |
2.86
(2.035)
|
3.57
(2.709)
|
2.00
(NA)
|
2.75
(0.957)
|
| Week 4 |
1.00
(NA)
|
3.17
(1.722)
|
||
| Week 6 |
4.14
(4.598)
|
4.13
(3.681)
|
||
| Week 8 |
1.00
(NA)
|
3.33
(2.160)
|
||
| Week 9 |
2.50
(2.510)
|
3.23
(2.204)
|
3.00
(NA)
|
2.25
(0.957)
|
| Week 12 |
2.20
(1.789)
|
3.92
(3.315)
|
1.00
(NA)
|
4.50
(3.209)
|
| Week 24 |
2.80
(1.304)
|
3.17
(2.137)
|
1.00
(NA)
|
2.80
(1.789)
|
| Week 36 |
2.25
(2.217)
|
4.50
(2.646)
|
1.00
(NA)
|
2.25
(1.893)
|
| Week 40 |
2.25
(1.893)
|
|||
| Week 48 |
3.00
(0.816)
|
4.67
(1.528)
|
||
| Week 51 |
1.75
(1.708)
|
6.00
(3.000)
|
| Title | Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study |
|---|---|
| Description | |
| Time Frame | Part 2: Up to Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population, all participants who have received at least one dose of study drug and who have at least one post-baseline assessment of safety. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Serum TCZ Concentration in Part 2 of the Study |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population in Part 2, all participants who have received at least one dose of study drug in Part 2. Number analyzed is the number of participants with data available for analyses at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Baseline |
29.916
(35.8002)
|
44.210
(33.2547)
|
9.520
(NA)
|
53.622
(48.5163)
|
| Week 0 |
24.212
(13.1659)
|
|||
| Week 3 |
26.420
(21.1844)
|
37.239
(21.8192)
|
||
| Week 4 |
11.100
(NA)
|
17.718
(11.1580)
|
||
| Week 6 |
28.636
(13.5744)
|
30.482
(19.2402)
|
||
| Week 8 |
22.800
(NA)
|
17.578
(13.0611)
|
||
| Week 9 |
32.020
(6.3739)
|
26.962
(17.9122)
|
||
| Week 12 |
37.600
(20.5254)
|
44.763
(77.1798)
|
23.800
(NA)
|
15.442
(11.0714)
|
| Week 24 |
24.363
(20.3686)
|
20.842
(25.9417)
|
30.300
(NA)
|
16.030
(14.2124)
|
| Week 36 |
30.517
(18.6058)
|
19.733
(8.2218)
|
19.800
(NA)
|
12.903
(11.1808)
|
| Week 40 |
28.778
(16.0031)
|
|||
| Week 48 |
25.433
(34.3053)
|
22.950
(0.9192)
|
||
| Week 51 |
12.207
(8.5862)
|
10.945
(14.6449)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Mean (Standard Deviation) [score on a scale] |
0.0000
(0.00000)
|
0.0417
(0.09047)
|
0.0000
(NA)
|
0.0000
(0.00000)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. Number analyzed is the number of participants with data available for analyses at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Change from Baseline at Week 0 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 3 |
0.2500
(0.66144)
|
0.0167
(0.25384)
|
||
| Change from Baseline at Week 4 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 6 |
0.1071
(0.28347)
|
-0.0083
(0.07420)
|
||
| Change from Baseline at Week 8 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 9 |
0.2500
(0.51539)
|
-0.0268
(0.10022)
|
||
| Change from Baseline at Week 12 |
0.1250
(0.27951)
|
-0.0481
(0.09599)
|
0.0000
(NA)
|
0.0000
(0.00000)
|
| Change from Baseline at Week 15 |
0.1458
(0.35722)
|
0.1771
(0.54994)
|
||
| Change from Baseline at Week 16 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 18 |
0.1000
(0.22361)
|
0.2500
(0.85009)
|
||
| Change from Baseline at Week 20 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 21 |
0.0000
(0.00000)
|
0.2656
(0.90740)
|
||
| Change from Baseline at Week 24 |
0.1250
(0.27951)
|
-0.0750
(0.11180)
|
0.0000
(NA)
|
0.0000
(0.00000)
|
| Change from Baseline at Week 27 |
0.0000
(0.00000)
|
0.0000
(0.10206)
|
||
| Change from Baseline at Week 28 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 30 |
0.0000
(0.00000)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 32 |
0.0000
(NA)
|
0.0000
(0.00000)
|
||
| Change from Baseline at Week 33 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
||
| Change from Baseline at Week 36 |
0.0000
(0.00000)
|
0.0417
(0.07217)
|
0.0000
(NA)
|
0.0000
(0.00000)
|
| Change from Baseline at Week 39 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
||
| Change from Baseline at Week 40 |
0.0000
(0.00000)
|
|||
| Change from Baseline at Week 42 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
||
| Change from Baseline at Week 45 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
||
| Change from Baseline at Week 48 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
||
| Change from Baseline at Week 51 |
0.0000
(0.00000)
|
-0.0417
(0.07217)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Mean (Standard Deviation) [score on a scale] |
2.3
(3.95)
|
1.6
(2.29)
|
0.0
(NA)
|
2.5
(3.21)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All TCZ population, all participants who have received at least one dose of study drug. Number analyzed is the number of participants with data available for analyses at the given timepoint. |
| Arm/Group Title | Part 2: TCZ IV 12 mg/kg Q3W | Part 2: TCZ IV 8 mg/kg Q3W | Part 2: TCZ IV 12 mg/kg Q4W | Part 2: TCZ IV 8 mg/kg Q4W |
|---|---|---|---|---|
| Arm/Group Description | Participants received tocilizumab 12 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants received tocilizumab 8 mg/kg IV infusions Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 12 mg/kg Q4W up to Week 52 in Part 2 of the study. | Participants who completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. |
| Measure Participants | 7 | 15 | 1 | 6 |
| Change from Baseline at Week 0 |
0.0000
(NA)
|
-1.2
(1.60)
|
||
| Change from Baseline at Week 3 |
-0.3
(2.36)
|
2.0
(6.12)
|
||
| Change from Baseline at Week 4 |
0.0000
(NA)
|
-1.2
(1.26)
|
||
| Change from Baseline at Week 6 |
-1.6
(3.51)
|
2.2
(4.55)
|
||
| Change from Baseline at Week 8 |
0.0
(NA)
|
-0.5
(3.56)
|
||
| Change from Baseline at Week 9 |
8.4
(26.48)
|
0.1
(2.62)
|
||
| Change from Baseline at Week 12 |
-1.6
(3.58)
|
-0.7
(2.32)
|
0.0
(NA)
|
-1.2
(2.56)
|
| Change from Baseline at Week 15 |
-1.5
(3.67)
|
7.1
(29.34)
|
||
| Change from Baseline at Week 16 |
0.0
(NA)
|
-1.5
(1.97)
|
||
| Change from Baseline at Week 18 |
-1.4
(3.71)
|
6.9
(23.26)
|
||
| Change from Baseline at Week 20 |
0.0
(NA)
|
-1.6
(2.61)
|
||
| Change from Baseline at Week 21 |
0.0
(0.00)
|
9.9
(30.02)
|
||
| Change from Baseline at Week 24 |
-1.8
(4.02)
|
-0.8
(2.17)
|
0.0
(NA)
|
-1.0
(2.00)
|
| Change from Baseline at Week 27 |
0.0
(0.00)
|
0.3
(2.87)
|
||
| Change from Baseline at Week 28 |
0.0
(NA)
|
-1.2
(2.39)
|
||
| Change from Baseline at Week 30 |
0.0
(0.00)
|
-0.3
(2.52)
|
||
| Change from Baseline at Week 32 |
0.0
(NA)
|
5.4
(14.35)
|
||
| Change from Baseline at Week 33 |
25.0
(50.00)
|
0.0
(3.00)
|
||
| Change from Baseline at Week 36 |
0.3
(0.50)
|
0.0
(3.00)
|
0.0
(NA)
|
-2.0
(2.83)
|
| Change from Baseline at Week 39 |
0.3
(0.50)
|
-1.0
(1.73)
|
||
| Change from Baseline at Week 40 |
-2.7
(3.06)
|
|||
| Change from Baseline at Week 42 |
0.0
(0.00)
|
-0.7
(2.08)
|
||
| Change from Baseline at Week 45 |
0.0
(0.00)
|
0.3
(3.51)
|
||
| Change from Baseline at Week 48 |
0.0
(0.00)
|
0.7
(4.04)
|
||
| Change from Baseline at Week 51 |
0.0
(0.00)
|
0.3
(3.51)
|
Adverse Events
| Time Frame | Part 1 - Up to 24 weeks plus 12 weeks safety follow up; Part 2 - Up to 52 weeks plus 12 weeks safety follow up | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population, all participants who received at least one dose of study drug and who had at least one post-baseline assessment of safety. | |||||
| Arm/Group Title | Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W | |||
| Arm/Group Description | Participants received 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched 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 received 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 completed 5 consecutive infusions of Q3W and had a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality switched to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study. | |||
All Cause Mortality |
||||||
| Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | 0/7 (0%) | 0/15 (0%) | |||
Serious Adverse Events |
||||||
| Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/19 (5.3%) | 1/7 (14.3%) | 1/15 (6.7%) | |||
| Hepatobiliary disorders | ||||||
| HYPERTRANSAMINASAEMIA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Immune system disorders | ||||||
| HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Infections and infestations | ||||||
| PNEUMONIA | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Part 1: Tocilizumab (TCZ) Q2W | Part 2: TCZ IV 12 mg/kg Q3W/Q4W | Part 2: TCZ IV 8 mg/kg Q3W/Q4W | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/19 (84.2%) | 7/7 (100%) | 14/15 (93.3%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| LEUKOPENIA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 3/15 (20%) | 7 |
| NEUTROPENIA | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 | 3/15 (20%) | 4 |
| THROMBOCYTOPENIA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Ear and labyrinth disorders | ||||||
| EAR PAIN | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| EAR SWELLING | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| VERTIGO | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Eye disorders | ||||||
| CATARACT SUBCAPSULAR | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| EYE PAIN | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| VISION BLURRED | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| ABDOMINAL PAIN | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 1/15 (6.7%) | 1 |
| DIARRHOEA | 2/19 (10.5%) | 2 | 1/7 (14.3%) | 1 | 1/15 (6.7%) | 1 |
| VOMITING | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| ANAL FISSURE | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| NAUSEA | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| General disorders | ||||||
| ***NO CODING AVAILABLE*** | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| PYREXIA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 2 |
| FATIGUE | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| HEPATIC STEATOSIS | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| Immune system disorders | ||||||
| SEASONAL ALLERGY | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| HYPERSENSITIVITY | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| Infections and infestations | ||||||
| BRONCHITIS | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| CONJUNCTIVITIS | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 1/15 (6.7%) | 1 |
| CYSTITIS | 1/19 (5.3%) | 3 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| EAR INFECTION | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| ENTEROBIASIS | 2/19 (10.5%) | 2 | 1/7 (14.3%) | 2 | 0/15 (0%) | 0 |
| INFLUENZA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| LOWER RESPIRATORY TRACT INFECTION | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| MYCOPLASMA INFECTION | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| NASOPHARYNGITIS | 1/19 (5.3%) | 2 | 1/7 (14.3%) | 1 | 3/15 (20%) | 7 |
| PARONYCHIA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 2 |
| PHARYNGITIS | 0/19 (0%) | 0 | 2/7 (28.6%) | 2 | 0/15 (0%) | 0 |
| PNEUMONIA | 2/19 (10.5%) | 3 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| RHINITIS | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 2/15 (13.3%) | 2 |
| TONSILLITIS | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 1/15 (6.7%) | 1 |
| UPPER RESPIRATORY TRACT INFECTION | 3/19 (15.8%) | 4 | 0/7 (0%) | 0 | 3/15 (20%) | 5 |
| URINARY TRACT INFECTION | 2/19 (10.5%) | 2 | 2/7 (28.6%) | 3 | 2/15 (13.3%) | 2 |
| VIRAL RASH | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| ASYMPTOMATIC BACTERIURIA | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| FUNGAL SKIN INFECTION | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| GASTROENTERITIS | 1/19 (5.3%) | 2 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| IMPETIGO | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| OTITIS EXTERNA | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| OTITIS MEDIA | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| PNEUMONIA MYCOPLASMAL | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| RESPIRATORY TRACT INFECTION | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| TONSILLITIS STREPTOCOCCAL | 1/19 (5.3%) | 1 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 |
| Injury, poisoning and procedural complications | ||||||
| ARTHROPOD BITE | 3/19 (15.8%) | 4 | 2/7 (28.6%) | 2 | 0/15 (0%) | 0 |
| CONTUSION | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| FALL | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| HEAD INJURY | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| JOINT INJURY | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| LIGAMENT SPRAIN | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| RADIUS FRACTURE | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| SKIN ABRASION | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 2/15 (13.3%) | 2 |
| TRAUMATIC HAEMATOMA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Investigations | ||||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 | 2/15 (13.3%) | 2 |
| COMPLEMENT FACTOR C4 DECREASED | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 2/15 (13.3%) | 2 |
| EOSINOPHIL COUNT INCREASED | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| HEPATIC ENZYME INCREASED | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| LIVER FUNCTION TEST INCREASED | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| LYMPHOCYTE MORPHOLOGY ABNORMAL | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| ALANINE AMINOTRANSFERASE INCREASED | 2/19 (10.5%) | 2 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| LIVER FUNCTION TEST ABNORMAL | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| ROSEOLOVIRUS TEST POSITIVE | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| VITAMIN D DECREASED | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| IRON DEFICIENCY | 1/19 (5.3%) | 2 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| PAIN IN EXTREMITY | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| POLYARTHRITIS | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| STILL'S DISEASE | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 2/15 (13.3%) | 2 |
| SYNOVIAL CYST | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| SKIN PAPILLOMA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Nervous system disorders | ||||||
| HEADACHE | 1/19 (5.3%) | 1 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| SYNCOPE | 1/19 (5.3%) | 3 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
| Psychiatric disorders | ||||||
| FEAR OF INJECTION | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Reproductive system and breast disorders | ||||||
| DYSMENORRHOEA | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| CATARRH | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| COUGH | 2/19 (10.5%) | 3 | 1/7 (14.3%) | 1 | 2/15 (13.3%) | 2 |
| OROPHARYNGEAL PAIN | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 2/15 (13.3%) | 2 |
| RHINORRHOEA | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| TONSILLAR HYPERTROPHY | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| BLISTER | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| INGROWING NAIL | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| PETECHIAE | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| PRURITUS | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 2/15 (13.3%) | 2 |
| RASH | 3/19 (15.8%) | 3 | 2/7 (28.6%) | 2 | 0/15 (0%) | 0 |
| RASH PAPULAR | 0/19 (0%) | 0 | 1/7 (14.3%) | 1 | 0/15 (0%) | 0 |
| SKIN EXFOLIATION | 0/19 (0%) | 0 | 0/7 (0%) | 0 | 1/15 (6.7%) | 1 |
| PRURIGO | 1/19 (5.3%) | 1 | 0/7 (0%) | 0 | 0/15 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01734382
Other Study ID Numbers:
- WA28029
- 2012-000444-10
First Posted:
Nov 27, 2012
Last Update Posted:
Apr 24, 2020
Last Verified:
Apr 1, 2020