- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT00687804
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Düsseldorf, Alemania
- Novartis Investigative Site
-
-
-
-
-
Melbourne, Australia
- Novartis Investigative Site
-
-
-
-
-
Leuven, Bélgica
- Novartis Investigative Site
-
-
-
-
-
Ontario, Canadá
- Novartis Investigative Site
-
-
-
-
-
Barcelona, España
- Novartis Investigative Site
-
-
-
-
-
Paris, Francia
- Novartis Investigative Site
-
-
-
-
-
Athens, Grecia
- Novartis Investigative Site
-
-
-
-
-
Budapest, Hungría
- Novartis Investigative Site
-
-
-
-
-
Firenze, Italia
- Novartis Investigative Site
-
-
-
-
-
Ankara, Pavo
- Novartis Investigative Site
-
-
-
-
-
Amsterdam, Países Bajos
- Novartis Investigative Site
-
-
-
-
-
Upton, Reino Unido
- Novartis Investigative Site
-
-
-
-
-
Zurich, Suiza
- Novartis Investigational site
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: 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.
|
Experimental: 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
|
Comparador activo: 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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
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
Periodo de tiempo: Baseline through the end of study (Month 12)
|
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.
|
Baseline through the end of study (Month 12)
|
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 24 Month Extension Study
Periodo de tiempo: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
|
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]
|
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 24 Month Extension Study
Periodo de tiempo: Extension baseline (Month 12 -end of core study) to Month 36 (end of extension study) [24 Months]
|
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]
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Core Study: Categorized Change in Visual Acuity (Letters) of the Study Eye From Baseline at Month 12
Periodo de tiempo: Baseline to Month 12
|
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.
|
Baseline to Month 12
|
Core Study: Mean Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time
Periodo de tiempo: Baseline to Month 12
|
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.
|
Baseline to Month 12
|
Core Study: Mean Change From Baseline at Month 12 in Central Retinal Thickness of the Study Eye
Periodo de tiempo: Baseline to Month 12
|
Retinal thickness was measured using Optical Coherence Tomography (OCT).
The images were reviewed by a central reading center to ensure a standardized evaluation.
|
Baseline to Month 12
|
Core Study: Mean Change From Baseline in Patient-reported Visual Functioning
Periodo de tiempo: Baseline to Month 12
|
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.
|
Baseline to Month 12
|
Extension Study: Percentage of Participants With Ocular Adverse Events (AEs) in the Study Eye in the 36 Months of the Core and Extension Studies
Periodo de tiempo: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 months]
|
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]
|
Extension Study: Percentage of Participants With Non-Ocular Adverse Events (AEs) in the 36 Months of the Core and Extension Studies
Periodo de tiempo: Core baseline (Day 1 of the core study) to Month 36 (end of extension study) [36 Months]
|
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]
|
Extension Study: Mean Change From Extension Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Periodo de tiempo: Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
|
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.
|
Extension baseline (Month12 -end of core study), Month 36 (end of extension study)
|
Extension Study: Mean Change From Core Study Baseline in Best Corrected Visual Acuity (BCVA) at Month 36
Periodo de tiempo: Core baseline (Day 1 of the core study), Month 36 (end of extension study)
|
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.
|
Core baseline (Day 1 of the core study), Month 36 (end of extension study)
|
Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Nervioso
- Enfermedades de los ojos
- Manifestaciones neurológicas
- Degeneración retinal
- Enfermedades de la retina
- Degeneración macular
- Trastornos sensoriales
- Edema macular
- Edema
- Visión, Baja
- Trastornos de la visión
- Efectos fisiológicos de las drogas
- Agentes antineoplásicos
- Inhibidores de la angiogénesis
- Agentes moduladores de la angiogénesis
- Sustancias de crecimiento
- Inhibidores del crecimiento
- Ranibizumab
Otros números de identificación del estudio
- CRFB002D2301
- EUDRACT: 2007-004877-24
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Edema macular diabético
-
The Lowy Medical Research Institute LimitedDesconocidoPigmento macular | Teleangiectasia macularAlemania
-
University of Modena and Reggio EmiliaTerminadoDegeneración Macular Avanzada | Degeneración Macular Seca | Degeneración Macular Senil | Cicatriz macular | Degeneración macular no exudativaItalia
-
Vitreo-Retinal Associates, MichiganVan Andel Research InstituteTerminadoEdema macular diabético | Degeneración macular exudativaEstados Unidos
-
Innovent Biologics (Suzhou) Co. Ltd.SuspendidoEdema macular diabético | Degeneración macular relacionada con la edad neovascularPorcelana
-
Ashvattha Therapeutics, Inc.TerminadoEdema macular diabético | Degeneración macular relacionada con la edad neovascularAustralia
-
AiViva BioPharma, Inc.ReclutamientoEdema macular diabético | Degeneración macular relacionada con la edad neovascularEstados Unidos
-
Hoffmann-La RocheTerminadoEdema macular diabético | Degeneración macular relacionada con la edad neovascularEstados Unidos
-
Centre Hospitalier Intercommunal CreteilTerminadoDegeneración Macular Exudativa Ojo Izquierdo | Degeneración Macular Exudativa Ojo DerechoFrancia
-
Mid-Atlantic Retina Consultations, Inc.West Virginia UniversityDesconocidoEdema macular diabético | Degeneración macular relacionada con la edad neovascularEstados Unidos
-
Daiichi Sankyo, Inc.TerminadoEdema macular diabético | Degeneración macular relacionada con la edad neovascularEstados Unidos
Ensayos clínicos sobre Ranibizumab
-
University of Campania "Luigi Vanvitelli"Terminado
-
University of Illinois at ChicagoGenentech, Inc.RetiradoGlaucoma | Glaucoma neovascular | Glaucoma de nueva aparición | Glaucoma Neovascular de Nuevo Inicio
-
Lupin Ltd.ReclutamientoDegeneración macular relacionada con la edad neovascularIndia
-
Hawaii Pacific HealthGenentech, Inc.TerminadoVasculopatía coroidea polipoidea | PCVEstados Unidos
-
New England Retina AssociatesGenentech, Inc.TerminadoMelanoma coroideoEstados Unidos
-
Especialistas en Retina Medica y Quirurgica Grupo...Centro de Retina Medica y Quirurgica S.C.TerminadoEdema macular diabéticoArgentina, México
-
Instituto de Olhos de GoianiaTerminadoEnfermedades de la retina
-
Samsung Bioepis Co., Ltd.TerminadoLa degeneración macular relacionada con la edadCorea, república de, Estados Unidos, India, Alemania, Hungría, Reino Unido, Chequia, Polonia, Federación Rusa
-
Pusan National University HospitalNovartisTerminadoDegeneración macular exudativa relacionada con la edadCorea, república de
-
NovartisTerminadoLa degeneración macular relacionada con la edadSuiza