Clinical Trial Results:
A MULTICENTER, OPEN-LABEL, SINGLE ARM, LONG-TERM EXTENSION STUDY OF WA19926 TO DESCRIBE SAFETY DURING TREATMENT WITH TOCILIZUMAB IN PATIENTS WITH EARLY, MODERATE TO SEVERE RHEUMATOID ARTHRITIS
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Summary
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EudraCT number |
2011-006125-14 |
Trial protocol |
HU |
Global end of trial date |
18 Dec 2014
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Results information
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Results version number |
v1 |
This version publication date |
08 Jul 2016
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First version publication date |
08 Jul 2016
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Other versions |
v2 |
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 |
ML28146
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01649804 | ||
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 |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, 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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Dec 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective for this study was to evaluate the long term safety of tocilizumab therapy in all enrolled participants.
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Protection of trial subjects |
All study subjects were required to read and sign an informed consent form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jul 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 |
Hungary: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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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) |
0
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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) |
11
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From 65 to 84 years |
1
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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 |
A total number of 12 participants were enrolled in Hungary. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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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 |
Tocilizumab (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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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 (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study.
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Baseline characteristics reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Tocilizumab (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Tocilizumab (RoActemra/Actemra) 8 milligram/kilogram (mg/kg) intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study. | ||
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End point title |
Percentage of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs of Special Interest (AESIs) [1] | ||||||||||||||
End point description |
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Adverse Events of Special Interest for this study were: Serious and/or medically significant infections; myocardial infarction/Acute coronary syndrome; Gastrointestinal perforation; Malignancies; Anaphylaxis/hypersensitivity reactions; Demyelinating disorders; Stroke and Serious and/or medically significant bleeding and hepatic events. Analysis population included all the enrolled participants in the study.
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End point type |
Primary
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End point timeframe |
End of Study (Week 104 or early withdrawal)
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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: Statistical analysis was not performed as planned. |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Disease Activity Index 28 Erythrocyte Sedimentation Rate (DAS28-ESR) | ||||||||||||||||||||||||
End point description |
The DAS28 (ESR) score is a measure of the participant's disease activity. It is calculated using the tender joint count (28 joints), swollen joint count (28 joints), erythrocyte sedimentation rate (ESR) and general health status. The DAS28-ESR scale ranges from 0 to 10, where higher scores represent higher disease activity. Analysis population included all the enrolled participants in the study.
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End point type |
Secondary
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End point timeframe |
Screening and End of Study (Week 104 or early withdrawal)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Number of Participants With Remission, Low, Medium, and High Disease Activity, as Measured by Simplified Disease Activity Index (SDAI) | ||||||||||||||||||||||||
End point description |
The SDAI was defined as the numerical sum of 5 outcome parameters: tender and swollen joint count (based on a 28-joint assessment), participant and physician global assessment of disease activity on a 100 millimeter (mm) Visual analogue scale (VAS) (VAS; 0 = no disease activity and 100 = worst disease activity) and level of C-reactive protein (CRP) (milligram per deciliter [mg/dl], normal < 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI <=3.3 indicates clinical remission, >3.4 to 11 = low disease activity, >11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity. Analysis population included all the enrolled participants in the study.
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End point type |
Secondary
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End point timeframe |
Screening and End of Study (Week 104 or early withdrawal)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Number of Participants With Decreased, Unchanged, and Increased Tender Joint Count (TJC) | ||||||||||||||||||||
End point description |
Tender joint count was performed by a skilled assessor, evaluating 68 joints for tenderness. Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.
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End point type |
Secondary
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End point timeframe |
Week 12 and Week 104
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of Participants With Decreased, Unchanged, and Increased Swollen Joint Count (SJC) | ||||||||||||||||||||
End point description |
Swollen joint count was performed by a skilled assessor, evaluating 66 joints for swelling. Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.
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End point type |
Secondary
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End point timeframe |
Week 12 and Week 104
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Time to Rheumatoid Arthritis (RA) Flare | ||||||||
End point description |
RA flare was defined as any worsening of the participant’s disease activity that in the opinion of the Investigator required treatment intensification beyond supportive therapy which included restarting of the study drug treatment. Time to RA flare was defined as the period of drug-free remission until documentation of RA flare. Data were not analyzed as there were no participants who had achieved clinical remission during the study.
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End point type |
Secondary
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End point timeframe |
End of Study (Week 104 or early withdrawal)
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| Notes [2] - No participant had achieved clinical remission during the study hence data was not analyzed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Clinical Remission | ||||||||
End point description |
Clinical remission was based on DAS28 (ESR) and SDAI. DAS28 (ESR) score is calculated using TJC (28 joints), SJC (28 joints), ESR and general health status. DAS28-ESR scale ranges from 0-10, where higher scores represent higher disease activity. DAS28 <=3.2 implied low disease activity, DAS >3.2 to 5.1 implied moderate disease activity and DAS >5.1 implied high disease activity, and DAS28 <2.6 = clinical remission. SDAI was defined as numerical sum of 5 outcome parameters: tender and swollen joint count (based on 28-joint assessment),participant and physician global assessment of disease activity on 100 mm VAS (VAS; 0 =no disease activity and 100= worst disease activity) and level of C-reactive protein (CRP) (mg/dl, normal < 1 mg/dl). SDAI total score = 0-86 where a higher score reflects worsening disease. SDAI <=3.3 indicates clinical remission,>3.4 to 11 = low disease activity,>11 to 26 = moderate disease activity, and >26 = high (or severe) disease activity.
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End point type |
Secondary
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End point timeframe |
End of Study (Week 104 or early withdrawal)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Decreased, Unchanged, and Increased Participants Global Assessment of Disease Activity | ||||||||||||||||||||
End point description |
The participant global assessment of disease activity was measured using a 100 mm VAS ranging from 0=very good to 100=very bad. Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.
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End point type |
Secondary
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End point timeframe |
Week 12 and Week 104
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of Participants With Decreased, Unchanged, and Increased Participant Global assessment of Pain | ||||||||||||||||||||
End point description |
A participant's overall assessment of pain on a VAS was assessed with a question concerning the amount of pain due to arthritis. Pain was assessed on a 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). Analysis population included all the evaluable participants for this outcome measure. "n" included all the participants analyzed on that particular time point.
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End point type |
Secondary
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End point timeframe |
Week 12 and Week 104
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Health Assessment Questionnaire Disability Index (HAQ-DI) | ||||||||
End point description |
The Health Assessment Questionnaire Disability Index (HAQ-DI) is a participant-completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 4 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered.Analysis population included all the enrolled participants in the study.
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End point type |
Secondary
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End point timeframe |
End of Study (Week 104 or early withdrawal)
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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 |
End of Study (Week 104 or early withdrawal)
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Adverse event reporting additional description |
An AE was any untoward medical occurrence in a study participant administered a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.0
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Reporting groups
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Reporting group title |
Tocilizumab
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Reporting group description |
Tocilizumab (RoActemra/Actemra) 8 mg/kg intravenously every 4 weeks for 104 weeks. Dose could be reduced due to safety reasons at any time during the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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 | |||
