Clinical Trial Results:
A Phase I Pharmacokinetic and Safety Study of Tocilizumab (TCZ) in Patients Less Than 2 Years Old with Active Systemic Juvenile Idiopathic Arthritis (sJIA)
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Summary
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EudraCT number |
2015-000435-33 |
Trial protocol |
DE HU BE ES PL GB FR |
Global end of trial date |
13 Jul 2017
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Results information
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Results version number |
v3(current) |
This version publication date |
25 Jan 2018
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First version publication date |
12 Feb 2017
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Other versions |
v1 , v2 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NP25737
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01455701 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
28 Jul 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Jul 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jul 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the pharmacokinetics of tocilizumab over 12 weeks in participants less than 2 years of age with sJIA.
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Protection of trial subjects |
The investigator ensured that this study was conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study fully adhered to the principles outlined in current “Guideline for Good Clinical Practice” International Conference on Harmonization (ICH) Tripartite Guideline or with local law if it afforded greater protection to the participant.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
26 Oct 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Argentina: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
11
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
11
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
Total 11 participants were enrolled, all of which were treated by tocilizumab. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Tocilizumab | ||||||||||||
Arm description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants had the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants received tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reached 2 years of age or had been treated for one year from baseline, whichever was longer. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
RO4877533
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Other name |
RoActemra; Actemra
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Tocilizumab was administered as indicated in the arm description.
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Period 2
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Period 2 title |
Optional Extension Period
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Is this the baseline period? |
No | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Tocilizumab | ||||||||||||
Arm description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants had the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants received tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reached 2 years of age or had been treated for one year from baseline, whichever was longer. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
RO4877533
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Other name |
RoActemra; Actemra
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Tocilizumab was administered as indicated in the arm description.
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Baseline characteristics reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants had the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants received tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reached 2 years of age or had been treated for one year from baseline, whichever was longer. | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants had the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants received tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reached 2 years of age or had been treated for one year from baseline, whichever was longer. | ||
Reporting group title |
Tocilizumab
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Reporting group description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants had the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants received tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reached 2 years of age or had been treated for one year from baseline, whichever was longer. | ||
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End point title |
Maximum Serum Concentration (Cmax) of Tocilizumab [1] | ||||||||
End point description |
Pharmacokinetic profile of tocilizumab was evaluated in terms of model predicted Cmax at steady state. Pharmacokinetic-evaluable population included all participants who provided at least one serum pharmacokinetic sample with valid concentration data.
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End point type |
Primary
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End point timeframe |
Pre-infusion (Hour 0) on Days 1, 15, 29, 43, 57, 71, and 85; at the end of infusion on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 (infusion length = 1 hour)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Minimum Serum Concentration (Cmin) of Tocilizumab [2] | ||||||||
End point description |
Pharmacokinetic profile of tocilizumab was evaluated in terms of observed Cmin at day 85. Pharmacokinetic-evaluable population.
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End point type |
Primary
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End point timeframe |
Pre-infusion (Hour 0) on day 85; (infusion length = 1 hour)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Model predicted Area Under the Serum Concentration-Time Curve from Time Zero to End of Dosing (AUCtau) of Tocilizumab [3] | ||||||||
End point description |
AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval (2 weeks). Pharmacokinetic-evaluable population.
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End point type |
Primary
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End point timeframe |
Pre-infusion (Hour 0) on Days 1, 15, 29, 43, 57, 71, and 85; at the end of infusion on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 (infusion length = 1 hour)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Adverse Events (AEs) and Serious AEs | ||||||||||||||||||||||||||||||||
End point description |
Number of participants with categorized AEs and serious AEs is reported. Detailed information of AEs is provided in the AEs section.
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End point type |
Secondary
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End point timeframe |
Baseline up to end of the main evaluation period (Week 12)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to end of the study (up week 52)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Participants received tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) for up to 10 weeks (a total of 6 infusions including one at baseline visit) in main evaluation period (12-week period) and 12 mg/kg every Q2W from week 12 until participant reached 2 years of age or had been treated for one year from baseline in optional extension period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Oct 2011 |
Protocol was amended for removal of sampling for anti-tocilizumab antibody, tocilizumab pharmacokinetics, and soluble interleukin-6 receptor (sIL-6R) at Week 18. |
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30 Jan 2012 |
Protocol was amended for making steroid tapering non-mandatory to remain stable for 6 weeks. |
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29 Oct 2014 |
Protocol was amended to change the time between diagnosis of sJIA and treatment with biologics from a 3-month delay to a 1-month delay. |
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01 Jun 2015 |
Protocol was amended to address concerns raised in the protocol review during the voluntary harmonization procedure in Europe. An exclusion criterion was amended to clarify that previous history of significant allergic or infusion reactions to any of the excipients listed in tocilizumab product labeling documents was part of this exclusion criterion. |
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10 Feb 2016 |
Protocol was amended mainly to clarify an inclusion criterion that it was intended to refer to the 1 month period of symptoms subsequent to the diagnosis of sJIA, before being considered for treatment with a biologic therapy, consistent with the updated American College of Rheumatology (ACR) recommendations for the treatment of sJIA that outlined the use of biologic therapy. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
