A Multicenter Open-Label Study of the Long-term Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Non-infectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 424
- 主要终点
- Respiratory Rate (Sitting): Mean Change (Respirations Per Minute) From Baseline To Final Visit
研究概览
简要总结
The purpose of this study is to evaluate the long term efficacy and safety of adalimumab participants with non-infectious intermediate-, posterior- or pan-uveitis.
详细描述
This study was initially planned to run for 78 weeks but was extended for ethical reasons, to avoid leaving participants untreated who had responded well to adalimumab treatment, so that participants were allowed to remain in the study until regulatory and/or reimbursement approval for the treatment of uveitis in adults was obtained for their respective countries. Data were collected through Week 366 (maximum), but because of decreasing sample size that became too small toward the end of the study to allow for meaningful conclusion, data cut off for efficacy analyses (intent to treat [ITT] population) occurred at Week 246, as less than 10% of participants in the ITT set had visits beyond this timepoint.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must have successfully enrolled in either study M10-877 or M10-880 and either met the endpoint of "Treatment Failure" or completed the study
排除标准
- •A participant will be excluded from this study if the participant discontinued from study M10-877 or M10-880 for any reasons other than having a Treatment Failure event
- •Participant with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial
- •Participants with intraocular pressure of >= 25 mmHg and on >= 2 glaucoma medications or evidence of glaucomatous optic nerve injury
- •Participant with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy
- •Participant with neovascular/wet age-related macular degeneration
- •Participant with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process
- •Participant with a systemic inflammatory disease that requires therapy with a prohibited immunosuppressive agent at the time of study entry
研究组 & 干预措施
Adalimumab
Participants received open label (OL) adalimumab 40 mg by subcutaneous (SC) injection every other week (eow) until the final visit.
干预措施: adalimumab (Drug)
结局指标
主要结局
Respiratory Rate (Sitting): Mean Change (Respirations Per Minute) From Baseline To Final Visit
时间窗: Baseline to Final Visit (Up to 366 weeks)
Respiratory rate (respirations per minute) was measured while the participant was sitting.
Number of Participants With Adverse Events
时间窗: Baseline to Final Visit (up to 366 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset date on or after the first dose of study drug and up to 70 days after the last dose. See the Adverse Event section for details.
Hematology: Number of Participants With Potentially Clinically Significant (PCS) Values
时间窗: Baseline to Final Visit (Up to 366 weeks)
PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations used include g=grams; L=liters.
Chemistry: Number of Participants With PCS Values
时间窗: Baseline to Final Visit (Up to 366 weeks)
PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations include ALT/SGPT=alanine aminotransferase/serum glutamate pyruvate transaminase; AST/SGOT=aspartate aminotransferase/serum glutamate oxaloacetate transaminase; g/L=grams/liter; mmol/L=millimoles/liter; ULN=upper limit of normal.
Pulse (Sitting): Mean Change (Beats Per Minute) From Baseline To Final Visit
时间窗: Baseline to Final Visit (Up to 366 weeks)
Heart rate (beats per minute) was measured while the participant was sitting.
Temperature (Sitting): Mean Change (Centigrade) From Baseline To Final Visit
时间窗: Baseline to Final Visit (Up to 366 weeks)
Temperature was measured while the participant was sitting.
Diastolic and Systolic Blood Pressure (Sitting): Mean Change (mmHg) From Baseline To Final Visit
时间窗: Baseline to Final Visit (Up to 366 weeks)
Blood pressure was measured while the participant was sitting. Abbreviations used include mmHg=millimeters of mercury.
次要结局
- Percentage of Participants in Quiescence Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants With Uveitis Flare Among Participants With Inactive Uveitis at Study Start(366 Weeks)
- Percentage of Participants With Uveitis Flare From Week 8 Through Last Visit Among Participants With Active Uveitis at Study Start(Weeks 8 to 246 (238 Weeks))
- Percentage of Participants With New Active Inflammatory Lesions or Grade ≥2 in Anterior Chamber (AC) Cells or Grade ≥2 in Vitreous Haze (VH) Over Time(Weeks 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants With Steroid-free Quiescence Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants in Non-quiescence (With/Without Change in Concomitant Medications Within 5 Days and With/Without Quiescence at Next Visit at Least 8 Weeks After Non-quiescence) Among Participants With Inactive Uveitis at Study Start(366 Weeks)
- Percentage of Participants in Non-quiescence (With/Without Change in Concomitant Medications Within 5 Days and With/Without Quiescence at Next Visit at Least 8 Weeks After Non-quiescence) Among Participants With Active Uveitis at Study Start(366 Weeks)
- Percentage of Participants Who Started Uveitis-related Systemic Corticosteroids During the Study(366 Weeks)
- Mean Daily Dose in Milligrams (mg) of Uveitis-related Systemic Corticosteroids in Participants With Active Uveitis Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Mean Daily Dose (mg) of Uveitis-related Systemic Corticosteroids in Participants With Inactive Uveitis Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percent Change in Mean Daily Dose of Uveitis-related Systemic Corticosteroids Relative to Week 0 in Participants With Inactive Uveitis Using Systemic Corticosteroids at Week 0 Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, and 198)
- Percent Change in Mean Daily Dose of Uveitis-related Systemic Corticosteroids Relative to Week 0 in Participants With Active Uveitis Using Systemic Corticosteroids at Week 0 Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants Not Using Systemic Corticosteroids Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants Without Worsening of Best Corrected Visual Acuity (BCVA) by ≥15 Letters on Early Treatment Diabetic Retinopathy Study (ETDRS) in Both Eyes Relative to Baseline Over Time Among Participants Who Had Inactive Uveitis at Study Entry(Weeks 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Percentage of Participants Without Worsening of BCVA by ≥15 Letters on the ETDRS in Both Eyes Relative to Week 8 Over Time Among Participants With Active Uveitis at Study Entry(Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)
- Mean of Both Eyes of the Logarithm of the Minimum Angle of Resolution (LogMAR) BCVA Over Time(Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246)