A 12 Month Core Study to Assess the Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema and a 24 Month Open-label Extension Study (RESTORE)
A Randomized, Double-masked, Multicenter, Laser-controlled Phase III Study Assessing the Efficacy and Safety of Ranibizumab (Intravitreal Injections) as Adjunctive and Mono-therapy in Patients With Visual Impairment Due to Diabetic Macular Edema
CRFB002D2301: The core study was designed to confirm the efficacy and safety of ranibizumab (0.5 mg) as adjunctive therapy when added to laser photocoagulation and/or mono-therapy in patients with visual impairment due to diabetic macular edema.
CRFB002D2301E1: A 24 month open-label extension study for participants who completed the 12 month core study evaluated the long-term safety and efficacy of ranibizumab (0.5 mg) as symptomatic treatment for visual impairment due to diabetic macular edema.
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Ontario、加拿大
- Novartis Investigative Site
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Budapest、匈牙利
- Novartis Investigative Site
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Athens、希腊
- Novartis Investigative Site
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Düsseldorf、德国
- Novartis Investigative Site
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Firenze、意大利
- Novartis Investigative Site
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Leuven、比利时
- Novartis Investigative Site
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Paris、法国
- Novartis Investigative Site
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Melbourne、澳大利亚
- Novartis Investigative Site
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Ankara、火鸡
- Novartis Investigative Site
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Zurich、瑞士
- Novartis Investigational site
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Upton、英国
- Novartis Investigative Site
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Amsterdam、荷兰
- Novartis Investigative Site
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Barcelona、西班牙
- Novartis Investigative Site
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Visual acuity impairment
- Diabetic macular edema in at least one eye
- Type 1 or type 2 diabetes mellitus
- Medication for the diabetes treatment must be stable for the last 3 months
Exclusion Criteria:
- Patients with uncontrolled systemic or ocular diseases
- Laser photocoagulation in the study eye for the last 3 months
- Any history of any intraocular surgery in the study eye within the past 3 months
- Blood pressure > 160/100 mmHg
Extension Inclusion Criteria:
-Completion of the Core Study
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Ranibizumab 0.5 mg
Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met: Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits. Patients also received sham laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes. In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy. |
0.5 mg ranibizumab administered by intravitreal injection.
Laser photocoagulation treatment
Sham to laser procedure.
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实验性的:Ranibizumab 0.5 mg + laser
Ranibizumab 0.5 mg was administered monthly by intravitreal injection in the study eye for 3 months. After the third injection, treatment was suspended if either one of the following criteria was met: Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits. Patients also received active laser treatment on Day 1 and subsequently at intervals of at least 3 months, if deemed necessary by the evaluating physician. Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes. In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy. |
0.5 mg ranibizumab administered by intravitreal injection.
Laser photocoagulation treatment
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有源比较器:Laser
Laser photocoagulation treatment was administered on Day 1 and at intervals of at least 3 months, if deemed necessary by the physician. Patients also received monthly sham intravitreal injection in the study eye for 3 consecutive months. After the third injection, treatment was suspended if either one of the following criteria was met: Improvement in best corrected visual acuity (BCVA) could not be attributed to treatment at the last 2 visits, in the opinion of the investigator, or BCVA > 84 letters (approximate Snellen equivalent of 20/20) was observed at the last 2 last visits. Active/sham laser treatment was always administered before (sham) intravitreal injections. The minimum interval between the 2 treatments was 30 minutes. In the extension study at the investigator's discretion, patients received open-label ranibizumab 0.5 mg intravitreal injections once a month until stable vision was reached (a maximum of 24 injections) and could receive laser therapy. |
0.5 mg ranibizumab administered by intravitreal injection.
Laser photocoagulation treatment
Sham to ranibizumab administered as an intravitreal injection.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Core Study: Difference Between the Baseline Level of Visual Acuity (Letters) of the Study Eye and the Mean Visual Acuity Averaged Over All Monthly Post-baseline Assessments From Month 1 to Month 12
大体时间:Baseline through the end of study (Month 12)
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Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction.
VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
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Baseline through the end of study (Month 12)
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Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
大体时间:Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
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Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about adverse events can be found in the Adverse Event section. |
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
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Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
大体时间:Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
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Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about adverse events can be found in the Adverse Event section. |
Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
大体时间:Baseline to Month 12
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Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction.
VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
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Baseline to Month 12
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Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
大体时间:Baseline to Month 12
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Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction.
VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
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Baseline to Month 12
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Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
大体时间:Baseline to Month 12
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Retinal thickness was measured using Optical Coherence Tomography (OCT).
The images were reviewed by a central reading center to ensure a standardized evaluation.
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Baseline to Month 12
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Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
大体时间:Baseline to Month 12
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The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life.
The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision.
The scores on the subscales were added together for a total score, which ranged from 0 to 100.
A higher score indicated improvement in quality of life due to vision function.
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Baseline to Month 12
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Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
大体时间:Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
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Participants with ocular (occurring in the eye) serious adverse events (SAEs) and non-serious AEs in the study eye. The study eye is the eye that received the treatment. AEs are the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about adverse events can be found in the Adverse Event section. |
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
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Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
大体时间:Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
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Participants with non-ocular (not occurring in the eye) serious adverse events (SAEs) and non-serious AEs. AEs are the appearance or worsening of of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. A serious adverse event is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant. Additional information about Adverse Events can be found in the Adverse Event section. |
Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
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Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
大体时间:Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
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Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction.
VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
An increase in the number of letters read correctly indicates improvement.
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Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
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Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
大体时间:Core baseline (Day 1 of the core study), Month 36 (end of extension study)
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Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction.
VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters.
An increase in the number of letters read correctly indicates improvement.
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Core baseline (Day 1 of the core study), Month 36 (end of extension study)
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合作者和调查者
赞助
出版物和有用的链接
一般刊物
- Bressler NM, Varma R, Mitchell P, Suner IJ, Dolan C, Ward J, Ferreira A, Ehrlich JS, Turpcu A. Effect of Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic Macular Edema: Report From RESTORE, RIDE, and RISE Trials. JAMA Ophthalmol. 2016 Feb;134(2):160-6. doi: 10.1001/jamaophthalmol.2015.4636.
- Mitchell P, Massin P, Bressler S, Coon CD, Petrillo J, Ferreira A, Bressler NM. Three-year patient-reported visual function outcomes in diabetic macular edema managed with ranibizumab: the RESTORE extension study. Curr Med Res Opin. 2015 Nov;31(11):1967-75. doi: 10.1185/03007995.2015.1081880. Epub 2015 Oct 6.
- Bressler NM, Varma R, Suner IJ, Dolan CM, Ward J, Ehrlich JS, Colman S, Turpcu A; RIDE and RISE Research Groups. Vision-related function after ranibizumab treatment for diabetic macular edema: results from RIDE and RISE. Ophthalmology. 2014 Dec;121(12):2461-72. doi: 10.1016/j.ophtha.2014.07.008. Epub 2014 Aug 20.
- Mitchell P, Bressler N, Tolley K, Gallagher M, Petrillo J, Ferreira A, Wood R, Bandello F; RESTORE Study Group. Patient-reported visual function outcomes improve after ranibizumab treatment in patients with vision impairment due to diabetic macular edema: randomized clinical trial. JAMA Ophthalmol. 2013 Oct;131(10):1339-47. doi: 10.1001/jamaophthalmol.2013.4592.
- Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.
- Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P; RESTORE Extension Study Group. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014 May;121(5):1045-53. doi: 10.1016/j.ophtha.2013.11.041. Epub 2014 Feb 1.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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Ranibizumab的临床试验
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Hoffmann-La Roche完全的
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Hoffmann-La Roche招聘中新生血管性年龄相关性黄斑变性比利时, 美国, 英国, 意大利, 阿根廷, 西班牙, 以色列, 澳大利亚, 奥地利, 巴西, 德国, 瑞士, 台湾, 法国
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Hoffmann-La Roche招聘中新生血管性年龄相关性黄斑变性 (nAMD)比利时, 大韩民国, 德国, 西班牙, 英国, 澳大利亚, 意大利, 阿根廷, 以色列, 奥地利, 巴西, 法国, 新加坡, 瑞士, 台湾, 火鸡