Safety Tolerability and Efficacy of Intravitreal LMG324 in the Treatment of Neovascular Age-Related Macular Degeneration
3 de junio de 2019 actualizado por: Alcon Research
An Open-label Single Ascending Dose and Randomized Double-Masked, Ranibizumab Controlled, Safety, Tolerability, and Efficacy Study of Intravitreal LMG324 in Subjects With Neovascular Age-Related Macular Degeneration
The purpose of this first-in-human study is to evaluate the safety and tolerability of single ascending doses of LMG324 to determine the maximum tolerated dose (MTD) in neovascular age-related macular degeneration (nvAMD) subjects.
Enrollment will be expanded at a safe and tolerated dose in treatment naïve nvAMD subjects to compare a single intravitreal (IVT) dose of LMG324 to ranibizumab 0.5 mg administered every 4 weeks for change from baseline in best-corrected visual acuity (BCVA) at Week 12 (Day 85).
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
The study will start with a single dose ascending (SAD) phase. LMG324 will be administered on Day 1 with no further treatment until implementation of standard of care (SoC) therapy. SoC therapy is ranibizumab 0.5 mg administered per label. Dose groups will be implemented sequentially to allow for safety review between the current and subsequent dose group. All treatments will be open-label, including ranibizumab used as SoC therapy.
In the enrollment expansion phase, subjects randomized to LMG324 arm will receive a single LMG324 IVT injection on Day 1 followed by sham (fake) IVT injections until implementation of SoC therapy. After implementation, SoC therapy will be applied monthly with sham injections applied at the interim planned visits. The enrollment expansion phase may start at a selected dose level whilst the dose escalation phase is still ongoing.
Tipo de estudio
Intervencionista
Inscripción (Actual)
25
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Texas
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Fort Worth, Texas, Estados Unidos, 76134
- Call Alcon Call Center for Trial Locations
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
50 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Must give written informed consent, be able to make the required study visits and follow instructions.
- Best corrected visual acuity (BCVA) of 34 letters (approximately 20/200 Snellen or better) in the non-study eye.
SAD population only:
- Subject's study eye must have a choroidal neovascularization (CNV) lesion due to age-related macular degeneration (AMD), either treatment naïve or previously treated, that can be expected to benefit, in the opinion of the investigator, from anti-vascular endothelial growth factor (anti-VEGF) therapy.
- Previously treated eyes must have a history of least 3 administrations of any intravitreal (IVT) anti-VEGF therapeutic for the treatment of CNV with the last injection administered ≥ 1 month prior to the planned administration of the study drug.
Enrollment expansion population only
- Subject's study eye must have untreated and active CNV lesion due to AMD.
- BCVA, between 73 - 23 letters, inclusive (approximate Snellen equivalent 20/40 - 20/320) in the study eye.
Exclusion Criteria:
SAD and enrollment expansion population
- Both eyes: any active ocular or periocular infection or active intraocular inflammation (eg, infectious blepharitis, infectious conjunctivitis, keratitis, scleritis, endophthalmitis).
- Study eye: current vitreous hemorrhage or a history of rhegmatogenous retinal detachment.
- Study eye: uncontrolled glaucoma (intraocular pressure [IOP] >25 mmHg on medication or according to Investigator's judgment).
SAD population only
- Presence of any contraindications, in the Investigator's opinion, to IVT anti-VEGF therapeutic administration.
Enrollment expansion population only
- Study eye: subject has received any approved or investigational treatment for exudative (wet) AMD other than vitamin supplements.
- Study eye: any current or history of macular or retinal disease other than exudative AMD
- Study eye: serous pigment epithelial detachment (PED) under the foveal center or retinal pigment epithelium (RPE) tear/rip.
- Study eye: any concurrent intraocular condition (eg, cataract, diabetic retinopathy) that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study.
- Study eye: other ocular diseases that, in the opinion of the Investigator, can compromise the visual acuity
- Study eye: Surgery, as specified in the protocol.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: LMG324
SAD: LMG324 administered as a single IVT injection in 1 eye (study eye) in 1 of 4 doses, with 15-day follow-up
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IVT injection
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Experimental: LMG324 + sham
Expansion: LMG324 administered as a single IVT injection in 1 eye (study eye), followed by sham injections, until implementation of SoC therapy as specified in the protocol, for 24 weeks
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IVT injection
Fake injection used for masking purposes
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Comparador activo: Lucentis + sham
Expansion: Ranibizumab 0.5 mg administered as monthly IVT injections in 1 eye (study eye) with interim sham injections, for 24 weeks
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Fake injection used for masking purposes
IVT injection
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Mean change from baseline in best corrected visual acuity (BCVA) at Day 85
Periodo de tiempo: Baseline, Day 85
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Baseline, Day 85
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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Percentage of LMG324-treated subjects with no identified SoC treatment need up to and including Day 85
Periodo de tiempo: Up to Day 85
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Up to Day 85
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Best Corrected Visual Acuity (BCVA)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Central subfield thickness total (CSFTtot)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Central subfield thickness neuro-retina (CFSTnr)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Lesion thickness
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Subretinal fluid with foveal involvement (SRFfi) thickness
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Retinal pigment epithelial detachment with foveal involvement (PEDfi) thickness
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area of lesion (associated with CNV)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area of CNV within a lesion
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration (AUC0-t)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Maximum observed maximum plasma concentration (Cmax)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Time to reach the maximum observed plasma concentration (Tmax)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Observed maximum plasma concentration following drug administration, by dose (Cmax/D)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Area under the plasma concentration-time curve divided by dose (AUC/D)
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Frequency of subjects with anti-LMG324 antibodies
Periodo de tiempo: Up to Day 169
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Up to Day 169
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Director de estudio: Clinical Scientist I, NIBR, Alcon Research
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
22 de julio de 2015
Finalización primaria (Actual)
29 de febrero de 2016
Finalización del estudio (Actual)
20 de mayo de 2016
Fechas de registro del estudio
Enviado por primera vez
20 de marzo de 2015
Primero enviado que cumplió con los criterios de control de calidad
24 de marzo de 2015
Publicado por primera vez (Estimar)
25 de marzo de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de junio de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
3 de junio de 2019
Última verificación
1 de junio de 2019
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- LMG324-2201
- 2014-005214-37 (Número EudraCT)
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. .