This randomized, double-blind, placebo-controlled study will compare the efficacy with regard to sustained remission and safety of tocilizumab and methotrexate, in combination or as monotherapy, in treatment-naïve patients with early rheumatoid arthritis. Patients will be randomized to receive either tocilizumab (8mg/kg iv every 4 weeks) plus weekly methotrexate (po in ascending doses), or tocilizumab (8mg/kg iv every 4 weeks) plus placebo, or methotrexate plus placebo. Anticipated time on study treatment is 2 years, and target sample size is 300.
Multi-center, randomized, double-blind, placebo-controlled (double placebo) three-arm parallel group, comparative study. Patients were randomized in a 1:1:1 ratio to one of the following treatments: * TCZ 8 milligram (mg)/kilogram (kg) + MTX (Group I: TCZ+MTX) * TCZ 8 mg/kg + placeboMTX (Group II: TCZ+placebo) * MTX + placeboTCZ (Group III: MTX+placebo) Randomization was stratified by participating center and baseline Disease Activity Score, scoring 28 joints (DAS28) level (\<5.1 vs. ≥5.1). Patients were evaluated every 4 weeks and at each visit a decision on dosage changes was made based on efficacy parameters (DAS28) and occurrence of adverse events (AEs). Patients received MTX/placeboMTX in climbing dosages. Hydroxychloroquine (HCQ) was added when remission was not reached with the maximum tolerable dosage (MTD) of MTX/placeboMTX. If after 12 additional weeks remission was not reached, HCQ was stopped and replaced by standard of care therapy (in Group I) or placebo therapy was replaced by the corresponding verum resulting in TCZ+MTX combination therapy (in Groups II and III). In case remission was reached, MTX/placeboMTX and TCZ/placeboTCZ had to be decreased. Patients were followed for a maximum of 24 months
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
317
orally weekly in ascending dosages, starting at 10mg/week
orally weekly
iv every 4 weeks
8mg/kg iv every 4 weeks
Unnamed facility
Alkmaar, Netherlands
Unnamed facility
Amersfoort, Netherlands
Unnamed facility
Amsterdam, Netherlands
Unnamed facility
Apeldoorn, Netherlands
Unnamed facility
Breda, Netherlands
Unnamed facility
Den Helder, Netherlands
Unnamed facility
Emmeloord, Netherlands
Unnamed facility
Gorinchem, Netherlands
Unnamed facility
Gouda, Netherlands
Unnamed facility
Groningen, Netherlands
...and 11 more locations
Percentage of Participants Achieving Sustained Remission Rate At Week 104
Sustained remission rate (SRR) is defined as Disease Activity Score 28 (DAS28) \<2.6 during ≥ 23 weeks and no more than 4 swollen joints (28 joint count) due to RA at Week 24 of remission, with the exception of up to 2 in-between DAS28 values which could be between 2.6 and 3.2. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.
Time frame: Week 104
Median Time to First Sustained Remission
It is the time to event analysis for the first period of sustained remission. Sustained remission is defined as DAS28 \<2.6 during ≥23 weeks and no more than 4 swollen joints (28 joint count) due to RA at Week 24 of remission, with the exception of up to 2 in-between DAS28 values which could be between 2.6 and 3.2. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen and tender joint counts (range 0-28), acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission.
Time frame: Up to Week 104
Mean Duration of First Sustained Remission
It is the duration of the first period of sustained DAS28 remission. Participants who switch treatment strategy before reaching sustained remission considered failures.
Time frame: Up to Week 104
Number of Participants Achieving Disease Activity Score 28 Remission at Weeks 12, 24, 52, and 104
The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores indicate worsening. DAS28 \<2.6 equals (=) remission. Participants with missing data at visits before early study termination or who stopped the study prematurely because of insufficient therapeutic response or safety reasons considered non-responders or who stopped the study for other reasons, response set to missing after early withdrawal.
Time frame: Weeks 12, 24, 52, and 104
Median Time to First Disease Activity Score 28 Remission
It is the time to event analysis for the first DAS28 remission.
Time frame: Up to Week 104
Percentage of Participants With Cumulative Remission Rate at Weeks 12, 24, 52, and 104
The DAS28 score is a measure of the subject's disease activity. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. Participants with missing data at visits before early study termination or who stopped the study prematurely because of insufficient therapeutic response or safety reasons considered non-responders or who stopped the study for other reasons, response set to missing after early withdrawal.
Time frame: Weeks 12, 24, 52, and 104
Mean Duration of First Disease Activity Score 28 Remission
It is the duration of the first period of DAS28 remission.
Time frame: Up to Week 104
Absolute Change From Baseline in Disease Activity Score 28 at Weeks 12, 24, 52, and 104
The DAS28 score is a measure of the participant's disease activity. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. Participants with missing data at visits before early study termination or who stopped the study prematurely because of insufficient therapeutic response or safety reasons considered non-responders or who stopped the study for other reasons, response set to missing after early withdrawal.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Median Change From Baseline in Clinical Disease Activity Index Score at Weeks 24, 52, and 104
The clinical disease activity index (CDAI) are continuous measures of RA disease activity. The CDAI is the numerical sum of four outcome parameters: tender joint count (TJC), swollen joint count (SJC) based on a 28-joint assessment; and patient's global assessment (PtGA) and physician's global assessment (PhGA) assessed on 0-10 cm visual analog scale (VAS). CDAI total score ranges from 0 to 76. CDAI \<= 2.8 indicates clinical remission, \>2.8 to 10 = low disease activity, \>10 to 22 = moderate disease activity, and \>22 = high (or severe) disease activity.
Time frame: From Baseline (Week 0) to Weeks 24, 52, and 104
Median Change From Baseline in Simplified Disease Activity Index Scores at Weeks 24, 52, and 104
The simplified disease activity index (SDAI ) are continuous measures of RA disease activity.The SDAI is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (assessed on 0-10 cm VAS), and C-Reactive Protein (CRP) (mg/dL). SDAI total score ranges from 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity.
Time frame: From Baseline (Week 0) to Weeks 24, 52, and 104
Number of Participants With Good European League Against Rheumatism Response Rate at Weeks 24, 52, and 104
European league against rheumatism (EULAR) response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual participant's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response : DAS28 at the time point =\<3.2 and improvement from baseline \> 1.2. Moderate response : DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and =\<1.2.
Time frame: Weeks 24, 52, and 104
Median Time to First European League Against Rheumatism Response
It is the time to first EULAR response. EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual participant's DAS28 as the measure of severity of disease.Good or moderate response is defined as follows: Good response : DAS28 at the time point ≤ 3.2 and improvement from baseline \> 1.2. Moderate response : DAS28 at the time point \> 3.2 and improvement from baseline \> 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline \> 0.6 and ≤ 1.2. Response 1 is defined as yes (good) versus no (moderate or no response). Response 2 is defined as yes (good or moderate) versus no (no response).
Time frame: Up to Week 104
Percentage of Participants With American College of Rheumatology 20 Response Rate at Weeks 12, 24, 52 and 104
American College of Rheumatology (ACR) 20 response is defined as a \>= 20% improvement (reduction) compared with baseline for both tender joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: patient's assessment of pain over the previous 24 hours: using a Visual Analog Scale (VAS) with left end of the line 0=no pain to right end of the line 100=unbearable pain; patient's global assessment of disease activity and physician's global assessment of disease activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time frame: Weeks 12, 24, 52 and 104
Percentage of Participants With American College of Rheumatology 50 Response Rate at Weeks 12, 24, 52 and 104
ACR50 response is defined as a \>=50% improvement (reduction) compared with baseline for both TJC68 and SJC66, as well as for three of the additional five ACR core set variables: patient's assessment of pain over the previous 24 hours: using a VAS with left end of the line 0=no pain to right end of the line 100=unbearable pain; patient's Global assessment of disease activity and physician's global assessment of disease activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time frame: Weeks 12, 24, 52 and 104
Percentage of Participants With American College of Rheumatology 70 Response Rate at Weeks 12, 24, 52 and 104
ACR70 response is defined as a \>=70% improvement (reduction) compared with baseline for both TJC68 and SJC66, as well as for three of the additional five ACR core set variables: patient's Assessment of pain over the previous 24 hours: using a VAS with left end of the line 0=no pain to right end of the line 100=unbearable pain; patient's global assessment of disease activity and physician's global assessment of disease activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; health assessment questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Time frame: Weeks 12, 24, 52 and 104
Percentage of Participants With American College of Rheumatology 90 Response Rate at Weeks 12, 24, 52 and 104
ACR90 response is defined as a \>=90% improvement (reduction) compared with baseline for both tender joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a VAS with left end of the line 0=no pain to right end of the line 100=unbearable pain; patient's global assessment of disease activity and physician's global assessment of disease activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; health assessment questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or erythrocyte sedimentation rate.
Time frame: Weeks 12, 24, 52 and 104
Mean Percent Change From Baseline in the Swollen Joint Count (SJC) at Weeks 12, 24, 52, and 104
The number of swollen joints among 22 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a swollen joint was scored as 1 and absence as 0. The total SJC was derived by the sum of the scores for a range of SJC from 0 (best possible score; no swollen joints) to 44 (worse possible score; all joints swollen).
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Percent Change From Baseline in the Tender Joint Count (TJC) at Weeks 12, 24, 52, and 104
The number of tender joints among 22 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a tender joint was scored as 1 and absence as 0. The total TJC was derived by the sum of the scores for a range of TJC from 0 (best possible score; no tender joints) to 44 (worse possible score; all tender joints).
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Percent Change From Baseline in Patient Health Visual Analog Scale at Weeks 12, 24, 52, and 104
Patient health visual analog scale is a component of ACR. It is measured using a visual analogue scale with scores ranging from 0 to 100 (higher scores indicate worse disease activity). An improvement (decrease) in the patient's global assessment based on disease activity relative to respective baseline values was analyzed.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Percent Change From Baseline in The Physician Health Visual Analog Scale at Weeks 12, 24, 52, and 104
Physician health visual analog scale is a component of ACR. It is measured using a visual analogue scale with scores ranging from 0 to 100 (higher scores indicate worse disease activity).An improvement (decrease) in the physician's global assessment based on disease activity parameter relative to respective baseline values was analyzed.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Percent Change From Baseline in Pain Visual Analog Scale at Weeks 12, 24, 52, and 104
Pain VAS is a component of ACR. VAS pain score calculated as 0 to 10 cm; where 0 = no pain, and 10 = worst possible pain.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Percent Change From Baseline in CRP at Weeks 12, 24, 52, and 104
CRP is a component of ACR. CRP is a marker of inflammation.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52, and 104
Mean Change From Baseline in Modified Sharp/Van Der Heijde Score at Weeks 52 and 104
The degree of joint damage was assessed using the van der Heijde modified total Sharp score (mTSS). The methodology quantifies the extent of bone erosions for 44 joints and joint space narrowing (JSN) for 42 joints, with higher scores representing greater damage. The independent read of X-ray images was performed by 2 primary readers. In case of discrepancy between the 2 primary readers, an adjudicator was involved. The mTSS can range from 0 to 448 with a higher score indicating more joint damage. A negative change score indicates improvement.
Time frame: From Baseline (Week 0) to Weeks 52 and 104
Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response
Insufficient therapeutic response (participants not responding to the drug as assessed by the physician) was selected by the investigator as a reason for the participant to withdraw from the study.
Time frame: Up to Week 104
Number of Participants With Change in The Therapy Strategy During The Study
Participants who switched treatment strategy from monotherapy (TCZ+ placebo MTX or MTX+ placebo TCZ treatment) to combination therapy (TCZ+MTX treatment) was reported. Also, participants who switched from verum therapy to standard of care was reported in the below table.
Time frame: From Baseline to Week 104
Mean Change From Baseline in The Dutch Consensus Health Assessment Questionnaire of Quality of Life at Weeks 12, 24, 52, and 104
The Dutch Consensus Health Assessment Questionnaire (DC-HAQ) disability index is a self-completed participant questionnaire with 8 domains specific for RA. It assesses a participant functional ability, with scores ranging from 0 (without any difficulty) to 3 (unable to do). A change from baseline of -0.22 is considered to be the minimal clinically important difference.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in The EuroQol Score of Quality of Life at Weeks 12, 24, 52 and 104
"EuroQol (EQ-5D) is a standard self-completed participant questionnaire that measures health outcome. The EQ-5D questionnaire consists of 2 parts: 1) EQ-5D with five dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Each dimension is rated on a 3-point response scale as 1 = no problems, 2 = some/moderate problems, 3 = extreme problems. The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, where '1' indicating full health and '0' representing dead. The positive values indicate that during the study the health status improved. 2) EQ-VAS on a scale of 0 to 100, where 0 = worst possible health status and 100 = best possible health status."
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in 36-Item Short Form Health Survey of Quality of Life at Weeks 12, 24, 52, and 104
The 36-Item Short Form Health Survey (SF-36) is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Summary (PCS) and Mental Component Summary (MCS) measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in Patient Global Health Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104
Patient global health VAS score ranges from 0 to 100 and a higher score indicates worse QoL. Patient global health VAS is a component of DAS28.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in Physician Global Health Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104
Physician global health VAS score ranges from 0 to 100 and a higher score indicates worse QoL. Physician global health VAS is a component of DAS28.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in Patient Pain Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104
Participants assessed their pain using a 0 to 10 horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 and is described as "no pain" and the right-hand extreme equals 10 as "unbearable pain" .The final VAS score will be derived by multiplying the original scores by 10.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in Patient General Wellbeing Visual Analog Scale Score of Quality of Life at Weeks 12, 24, 52, and 104
Participants assessed their general wellbeing using a 0 to 10 horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 and is described as " not active at all " and the right-hand extreme equals 10 as " very active " .The final VAS score will be derived by multiplying the original scores by 10.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Score of Quality of Life at Weeks 12, 24, 52, and 104
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participants response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the participant's health status.
Time frame: From Baseline (Week 0) to Weeks 12, 24, 52 and 104
Mean Change From Baseline in The Revised Illness Perception Questionnaire (IPQ-R) Score of Quality of Life at Week 12
The IPQ-R includes 9 domains (identity, acute or chronic timeline, consequences, personal and treatment control, illness coherence, timeline cyclical, emotional representations, and cause). For first 8 domains it scores as: 1(strongly disagree), 2(disagree), 3(neither agree/disagree), 4(agree), and 5(strongly agree), except identity as 1(yes) and 0(no). The sum of scores for identity, timeline, consequences, and cyclical domains are ranged from 0-16. High score represent strongly held beliefs about the number of symptoms attributed to RA, the chronicity of the condition, the negative consequences of the illness and the cyclical nature of the condition. The sum of scores for personal and treatment control, coherence dimensions, and emotional representations are ranged from 0-15. High score represent positive beliefs about the number of controllability of RA and a personal understanding of the condition. The data for 'Cause' domain was not considered for analysis in this study.
Time frame: From Baseline (Week 0) to Week 12
Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 24
The IPQ-R includes 9 domains (identity, acute or chronic timeline, consequences, personal and treatment control, illness coherence, timeline cyclical, emotional representations, and cause). For first 8 domains it scores as: 1(strongly disagree), 2(disagree), 3(neither agree/disagree), 4(agree), and 5(strongly agree), except identity as 1(yes) and 0(no). The sum of scores for identity, timeline, consequences, and cyclical domains are ranged from 0-16. High score represent strongly held beliefs about the number of symptoms attributed to RA, the chronicity of the condition, the negative consequences of the illness and the cyclical nature of the condition. The sum of scores for personal and treatment control, coherence dimensions, and emotional representations are ranged from 0-15. High score represent positive beliefs about the number of controllability of RA and a personal understanding of the condition. The data for 'Cause' domain was not considered for analysis in this study.
Time frame: From Baseline (Week 0) to Week 24
Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 52
The IPQ-R includes 9 domains (identity, acute or chronic timeline, consequences, personal and treatment control, illness coherence, timeline cyclical, emotional representations, and cause). For first 8 domains it scores as: 1(strongly disagree), 2(disagree), 3(neither agree/disagree), 4(agree), and 5(strongly agree), except identity as 1(yes) and 0(no). The sum of scores for identity, timeline, consequences, and cyclical domains are ranged from 0-16. High score represent strongly held beliefs about the number of symptoms attributed to RA, the chronicity of the condition, the negative consequences of the illness and the cyclical nature of the condition. The sum of scores for personal and treatment control, coherence dimensions, and emotional representations are ranged from 0-15. High score represent positive beliefs about the number of controllability of RA and a personal understanding of the condition. The data for 'Cause' domain was not considered for analysis in this study.
Time frame: From Baseline (Week 0) to Week 52
Mean Change From Baseline in The IPQ-R Score of Quality of Life at Week 104
The IPQ-R includes 9 domains (identity, acute or chronic timeline, consequences, personal and treatment control, illness coherence, timeline cyclical, emotional representations, and cause). For first 8 domains it scores as: 1(strongly disagree), 2(disagree), 3(neither agree/disagree), 4(agree), and 5(strongly agree), except identity as 1(yes) and 0(no). The sum of scores for identity, timeline, consequences, and cyclical domains are ranged from 0-16. High score represent strongly held beliefs about the number of symptoms attributed to RA, the chronicity of the condition, the negative consequences of the illness and the cyclical nature of the condition. The sum of scores for personal and treatment control, coherence dimensions, and emotional representations are ranged from 0-15. High score represent positive beliefs about the number of controllability of RA and a personal understanding of the condition. The data for 'Cause' domain was not considered for analysis in this study.
Time frame: From Baseline (Week 0) to Week 104
Number of Participants With Any Adverse Events, Any Serious Adverse Events, and Adverse Events Leading to Discontinuation
An adverse event is any untoward medical occurrence in a participant 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 , 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. A serious adverse event is defined as any event which was fatal (resulted in death), lifethreatening (with immediate risk of death), resulted in a new or prolongation of a current hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, considered medically significant by the investigator, required intervention to prevent one or more of the outcomes listed above.
Time frame: Up to Week 104
Number of Participants With Clinically Significant Laboratory Values at Week 12
Laboratory parameters included hematology, chemistry and lipids. Any treatment-emergent abnormal laboratory result accompanied by clinical symptoms or leading to a change in study medication or requiring a change in concomitant therapy was considered clinically significant. Participants with clinically significant laboratory values are reported in the below table.
Time frame: Week 12
Number of Participants With Clinically Significant Laboratory Values at Week 24
Laboratory parameters included hematology, chemistry and lipids. Any treatment-emergent abnormal laboratory result accompanied by clinical symptoms or leading to a change in study medication or requiring a change in concomitant therapy was considered clinically significant. Participants with clinically significant laboratory values are reported in the below table.
Time frame: Week 24
Number of Participants With Clinically Significant Laboratory Values at Week 52
Laboratory parameters included hematology, chemistry and lipids. Any treatment-emergent abnormal laboratory result accompanied by clinical symptoms or leading to a change in study medication or requiring a change in concomitant therapy was considered clinically significant. Participants with clinically significant laboratory values are reported in the below table.
Time frame: Week 52
Number of Participants With Clinically Significant Laboratory Values at Week 104
Laboratory parameters included hematology, chemistry and lipids. Any treatment-emergent abnormal laboratory result accompanied by clinical symptoms or leading to a change in study medication or requiring a change in concomitant therapy was considered clinically significant. Participants with clinically significant laboratory values are reported in the below table.
Time frame: Week 104
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