A Multicenter, Open-Label Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
概览
- 阶段
- 3 期
- 干预措施
- Tocilizumab
- 疾病 / 适应症
- Rheumatoid Arthritis
- 发起方
- Hoffmann-La Roche
- 入组人数
- 11
- 主要终点
- Percentage of Participants With Clinically Significant Physical Examinations and Vital Signs Abnormalities
- 状态
- 已完成
- 最后更新
- 9年前
概览
简要总结
This multicenter, open-label, single arm, interventional, long-term extension (LTE) study will evaluate the safety and efficacy of tocilizumab (TCZ, RoActemra/Actemra) in French participants with moderate to severe RA who have completed the Week 97 visit of WA22762 LTE study (NCT01194414) (EudraCT Number 2010-018375-22). Participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in disease activity score based on 28-joint count [DAS28] of greater than [>] 1.2 points) will continue TCZ treatment within this local LTE study for a maximum of 156 weeks of subcutaneous (SC) TCZ treatment, or until SC TCZ becomes commercially available, whichever occurs first.
研究者
入排标准
入选标准
- •Negative pregnancy test at screening and baseline
- •Participants who have completed the 97-week WA22762 LTE study on SC or intravenous (IV) TCZ and who experienced, at any time during WA22762, clinically significant improvement in DAS28 (\>1.2 points), and based on the investigator's judgment may continue to benefit from TCZ treatment in this study investigating the SC formulation
- •No current or recent adverse events or laboratory findings preventing the use of the study drug dose of TCZ 162 mg SC at baseline visit
- •Receiving treatment on an outpatient basis
- •Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception during the study and for at least 3 months following the last dose of study drug
- •Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the recommended dose are permitted if on stable dose regimen for greater than and equal to (\>/=) 4 weeks prior to baseline
- •Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed
排除标准
- •Participants who have prematurely withdrawn from the WA22762 LTE study for any reason
- •Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
- •Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell co stimulation modulator since the last administration of study drug in the WA22762 LTE study
- •Immunization with a live/attenuated vaccine since the last administration of study drug in the WA22762 LTE study
- •Diagnosis, since last WA22762 visit (Week 97), of rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjörgen's syndrome with RA is permitted
- •Diagnosis, since last WA22762 visit (Week 97), of inflammatory joint disease other than RA
- •Uncontrolled disease states, such as asthma or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
- •Evidence of serious uncontrolled concomitant disease
- •Known active current or history of recurrent infection
- •Primary or secondary immunodeficiency (history of or currently active)
研究组 & 干预措施
Tocilizumab
Moderate to severe rheumatoid arthritis participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in DAS28 of \>1.2 points) will continue tocilizumab treatment within this local LTE study for a maximum of 156 weeks, or until SC TCZ becomes commercially available, whichever occurs first.
干预措施: Tocilizumab
结局指标
主要结局
Percentage of Participants With Clinically Significant Physical Examinations and Vital Signs Abnormalities
时间窗: Baseline up to approximately 142 weeks
Criteria for potentially clinically important (PCI) change in vital signs: heart rate value of less than (\<) 40 beats per minute and value greater than (\>) 150 beats per minute, systolic blood pressure (SBP) of \< 80 or \>210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of \<40 or \>130 mmHg, body temperature \<32 or \> 40 degrees Celsius, respiratory rate of \<10 or \> 50 breaths/minute and criteria for PCI change in physical examination: \>/=10% increase or decrease of body weight in kilograms (kg).
Percentage of Participants With Adverse Events of Special Interest (AESIs)
时间窗: Baseline up to approximately 142 weeks
Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.
Percentage of Participants With AEs Leading to TCZ Discontinuation, Interruption, or Dose Modification
时间窗: Baseline up to approximately 142 weeks
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Percentage of participants with AE causing drug discontinuation, interruption and increase or decrease in dose of drug was presented.
Percentage of Participants With Anti-TCZ Antibodies
时间窗: Baseline up to approximately 142 weeks
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to approximately 142 weeks
An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A SAE was any untoward medical occurrence that at any dose resulted in death, was life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, and congenital anomaly/birth defect. AEs included SAEs as well as non-serious AEs.
Percentage of Participants With AEs and SAEs Related to TCZ
时间窗: Baseline up to approximately 142 weeks
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included SAEs as well as non-serious AEs. Causality of AEs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on drug cessation \[DC\], relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs). AEs with causality of certain, probable/likely, and possible were considered TCZ related.
Percentage of Participants With Clinically Significant Laboratory Abnormalities
时间窗: Baseline up to approximately 142 weeks
Criteria for laboratory tests clinically significant abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(\< 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/greater than \[\>\]1.5\*upper limit of normal \[ULN\]); platelets (\<0.5\*LLN\>\</0\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN\>\</0\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN), total protein, albumin (\<0.8\*LLN\>\</0\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN\>\</0\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN\>\</0\>1.1\*ULN); urine RBCs, urine white blood cells (WBCs) (\> or equal\[=\]20 high-powered field), urine bacteria \>20 high-powered field. Overall percentage of participants with any clinically significant laboratory abnormality was reported.
Percentage of Participants With AESIs Related to TCZ
时间窗: Baseline up to approximately 142 weeks
AESI for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Percentage of participants with AESI related to the drug were presented. Causality of AESIs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on DC, relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs). AESIs with causality of certain, probable/likely, and possible were considered TCZ related.
次要结局
- Change From Baseline in TJC(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Time to Concomitant Corticosteroid Discontinuation(Baseline up to approximately 142 weeks)
- Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Change From Baseline in SJC(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Percentage of Participants With Clinical Remission(Week 48, 108)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Change From Baseline in Simplified Disease Activity Index (SDAI) Score(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Percentage of Participants With Concomitant Corticosteroid Dose Reduction(Baseline up to approximately 142 weeks)
- Time to Concomitant Corticosteroid Dose Reduction(Baseline up to approximately 142 weeks)
- Change From Baseline in PtGA of Disease Activity(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Change From Baseline in CRP(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Percentage of Participants With Concomitant Corticosteroid Discontinuation(Baseline up to approximately 142 weeks)
- Change From Baseline in Patient's Assessment of Pain(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Change From Baseline in Physician's Global Assessment of Disease Activity(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))
- Change From Baseline in ESR(Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120))