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.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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Upton、イギリス
- Novartis Investigative Site
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Firenze、イタリア
- Novartis Investigative Site
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Amsterdam、オランダ
- Novartis Investigative Site
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Melbourne、オーストラリア
- Novartis Investigative Site
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Ontario、カナダ
- Novartis Investigative Site
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Athens、ギリシャ
- Novartis Investigative Site
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Zurich、スイス
- Novartis Investigational site
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Barcelona、スペイン
- Novartis Investigative Site
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Düsseldorf、ドイツ
- Novartis Investigative Site
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Budapest、ハンガリー
- Novartis Investigative Site
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Paris、フランス
- Novartis Investigative Site
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Leuven、ベルギー
- Novartis Investigative Site
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Ankara、七面鳥
- Novartis Investigative Site
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的: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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実験的: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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アクティブコンパレータ: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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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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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
時間枠: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
時間枠: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
時間枠: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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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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協力者と研究者
スポンサー
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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