Clinical Trial Results:
Tocilizumab SC in Patients with Active Rheumatoid Arthritis and Inadequate Response to DMARDs. A Single-Arm, Open-Label Study to Evaluate Safety, Tolerability and Efficacy. In a Subgroup of Patients Inflammation Will Be Measured by Ultrasound.
|
Summary
|
|
EudraCT number |
2013-002007-34 |
Trial protocol |
FI DK SE |
Global end of trial date |
13 Sep 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
14 Sep 2017
|
First version publication date |
14 Sep 2017
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ML28691
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02046616 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
13 Sep 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 Sep 2016
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
This open-label, single-arm study was designed to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) tocilizumab (RoActemra/Actemra) as monotherapy or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) who are naive to tocilizumab. Participants received tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.
|
||
Protection of trial subjects |
This study was conducted in full conformance with the International Council for Harmonisation (ICH)-E6 (Guideline for Good Clinical Practice) and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study was designed to comply with the requirements of the ICH-E2A guideline (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting) and the European Union Clinical Trial Directive (2001/20/EC).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 May 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Denmark: 44
|
||
Country: Number of subjects enrolled |
Finland: 37
|
||
Country: Number of subjects enrolled |
Sweden: 25
|
||
Country: Number of subjects enrolled |
Norway: 27
|
||
Worldwide total number of subjects |
133
|
||
EEA total number of subjects |
133
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
103
|
||
From 65 to 84 years |
30
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||
Screening details |
One hundred thirty-three participants entered the 24-week Treatment Period. Those who completed treatment entered the Follow-Up (FU) Period for an additional 8 weeks. | ||||||||||||||||||
|
Period 1
|
|||||||||||||||||||
Period 1 title |
24-Week Treatment Period
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
|
Arm title
|
Tocilizumab Alone or Combined with Methotrexate or Other DMARD | ||||||||||||||||||
Arm description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 milligrams (mg), irrespective of body weight, administered subcutaneously weekly (QW) for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
RoActemra, Actemra
|
||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Tocilizumab 162 mg was administered subcutaneously QW.
|
||||||||||||||||||
|
|||||||||||||||||||
|
Period 2
|
|||||||||||||||||||
Period 2 title |
8-Week FU Period
|
||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
|
Arm title
|
Tocilizumab Alone or Combined with Methotrexate or Other DMARD | ||||||||||||||||||
Arm description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 mg, irrespective of body weight, administered subcutaneously QW for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Tocilizumab
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
RoActemra, Actemra
|
||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||
Dosage and administration details |
Tocilizumab 162 mg was administered subcutaneously QW.
|
||||||||||||||||||
|
|||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||
Reporting group title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
|||||||||||||||||||||||||||||||||
Reporting group description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 milligrams (mg), irrespective of body weight, administered subcutaneously weekly (QW) for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||
Subject analysis set title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
|||||||||||||||||||||||||||||||||
Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 mg, irrespective of body weight, administered subcutaneously QW for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity.
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
||
Reporting group description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 milligrams (mg), irrespective of body weight, administered subcutaneously weekly (QW) for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | ||
Reporting group title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
||
Reporting group description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 mg, irrespective of body weight, administered subcutaneously QW for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | ||
Subject analysis set title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 mg, irrespective of body weight, administered subcutaneously QW for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity.
|
||
|
|||||||||||||
End point title |
Change from Baseline in Clinical Disease Activity Index (CDAI) at Week 12 [1] | ||||||||||||
End point description |
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity. Intent-to-Treat (ITT) Set: all participants who were treated with at least one dose of SC tocilizumab. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||
| 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: Statistical analyses were exploratory and hence, are not reported here. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score | ||||||||||||||||||||||||
End point description |
DAS28-ESR was based on TJC, SJC, PGA of disease activity, and laboratory-derived ESR. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. The total DAS28-ESR score was transformed to a single score range of 0-10, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with American College of Rheumatology (ACR) Response | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
ACR response was assessed by percent improvement (20% for ACR20, 50% for ACR50, 70% for ACR70) in both TJC and SJC plus at least three of the following: physician assessment of disease activity, PGA of disease activity, PGA of pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and either ESR or C-reactive protein level. TJC and SJC were taken as the number of tender and swollen joints, out of 68 and 66 assessed joints, respectively. PGA and physician assessments were scored 0-100 mm on VAS, where higher scores indicate greater perceived disease activity (or pain). HAQ-DI was scored using participant responses to 20 questions assessing activities of daily living (ADLs), with total score scale of 0-3, where higher scores indicate increased functional disability. The percentage of participants meeting criteria for each level of ACR response was reported. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with European League Against Rheumatism (EULAR) Response | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EULAR response was assessed by change from baseline and absolute DAS28-ESR score. EULAR response classification was as follows: Good (change >1.2 with absolute score </=3.2), Moderate (change >1.2 with absolute score >3.2 or change >0.6 with absolute score </=5.1), None (change </=0.6 or absolute score >5.1). DAS28-ESR was based on TJC, SJC, and PGA of disease activity, and laboratory-derived ESR. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. The total DAS28-ESR score was transformed to a single score range of 0-10, where higher scores indicate increased disease activity. The percentage of participants meeting criteria for each level of EULAR response was reported. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Change from Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24 | ||||||||||||||||||||
End point description |
CDAI was derived as the sum of the following: TJC, SJC, PGA of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 mm and rounded to the nearest cm on a VAS, where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 16, 20, 24
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in Simplified Disease Activity Index (SDAI) | ||||||||||||||||||||||||
End point description |
SDAI was derived as the sum of the following: TJC, SJC, PGA of disease activity, physician assessment of disease activity, and laboratory-derived C-reactive protein level. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 mm and rounded to the nearest cm on a VAS, where higher scores indicate greater perceived disease activity. The total SDAI score range was 0-86, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity. ITT Set; only those who provided data at baseline and at least one post-baseline assessment were analyzed. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in TJC | ||||||||||||||||||||||||
End point description |
TJC was taken as the number of tender joints out of 28 assessed joints. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in SJC | ||||||||||||||||||||||||
End point description |
SJC was taken as the number of swollen joints out of 28 assessed joints. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants with At Least One Adverse Event Leading to Dosage Modification | ||||||||||||
End point description |
The percentage of participants with at least one adverse event leading to dose/frequency reduction or temporary dose hold was reported. ITT Set.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Number of Participants with Neutralizing Anti-Tocilizumab Antibodies | ||||||||
End point description |
Participants were evaluated for the presence of anti-tocilizumab antibodies. Confirmatory assays were performed in the case of a positive screen assay result. ITT Set; only those who provided data for at least one assessment were analyzed.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline to FU Week 8 (up to 32 weeks overall)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Tocilizumab Concentration | ||||||||||||||||
End point description |
Tocilizumab concentration was determined, averaged among all participants, and expressed in micrograms per milliliter (mcg/mL). ITT Set. Here “n” refers to number of participants with quantifiable tocilizumab concentration at the specified assessment.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Soluble Interleukin-6 Receptor (sIL-6R) Concentration | ||||||||||||||||
End point description |
sIL-6R concentration was determined, averaged among all participants, and expressed in nanograms per milliliter (ng/mL). ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in Patient Global Assessment of Disease Activity According to VAS | ||||||||||||||||||||||||
End point description |
PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in Patient Global Assessment of RA-Related Pain According to VAS | ||||||||||||||||||||||||
End point description |
PGA of RA-related pain was scored 0-100 mm on a VAS, where higher scores indicate greater perceived pain. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA-related pain. ITT Set; only those who provided data at baseline and at least one post-baseline assessment were analyzed. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Change from Baseline in HAQ-DI Score | ||||||||||||||||||||||||
End point description |
HAQ-DI consisted of 20 questions assessing ADLs in 8 domains (dress/groom, arise, eat, walk, reach, grip, hygiene) with each item rated 0 (no difficulty) to 3 (unable to do). The highest score recorded for any question in a domain determined the score for that domain, unless assistance was required. The total HAQ-DI score was the sum of domain scores divided by the number of domains answered/scored, for a single score range of 0-3, where higher scores indicate increased functional disability. Change from baseline was averaged among all participants. Negative values indicate improvement in ability to perform ADLs. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||
End point title |
Compliance with Treatment According to Percentage of Injections Administered | ||||||||
End point description |
Participants were provided with diary cards to record home injections. Compliance with treatment was calculated individually for each participant as the actual number of injections as a percentage of the planned number of injections (up to the point of discontinuation for those who discontinued study treatment prematurely) and then averaged among all participants. ITT Set.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline up to Week 24
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score | ||||||||||||||||||||||||||||||||||||||||
End point description |
FACIT-F consisted of 40 questions/statements assessing chronic illness therapy with special emphasis on fatigue over the past 7 days, with each item rated 0 (not at all) to 4 (very much). During score calculations, negatively-worded item scales (e.g., “I have a lack of energy”) were reversed so that higher scores indicated more favorable conditions. The total FACIT-F score was the sum of all item scores and ranged 0-160, and the brief FACIT-F score was the sum of 13 item scores and ranged 0-52, where higher scores indicate greater well-being. Change from baseline was averaged among all participants. Positive values indicate improvement in well-being. ITT Set. Here “n” refers to number of participants evaluable at the specified assessment.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to FU Week 8 (up to 32 weeks overall)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
ITT Set
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tocilizumab Alone or Combined with Methotrexate or Other DMARD
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All participants received tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs at a dose of 162 mg, irrespective of body weight, administered subcutaneously QW for 24 weeks. An additional 8 weeks were allotted for post-treatment evaluation of safety/immunogenicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
02 Sep 2015 |
The planned sample size was changed. |
||
12 Apr 2016 |
The period for post-study follow-up of adverse events was clarified. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
