International, Multicenter, Randomized, Double-blind, Comparative Clinical Study of the Efficacy, Safety, Pharmacokinetics, and Immunogenicity of GNR-067 and Lucentis® in Patients With Neovascular (Wet) Age-related Macular Degeneration
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Age Related Macular Degeneration (ARMD)
- Sponsor
- AO GENERIUM
- Enrollment
- 408
- Locations
- 9
- Primary Endpoint
- The proportion of patients (%) with an increase in the best-corrected visual acuity (BCVA) score on the ETDRS chart (measured using logMAR/Snellen chart) of 15 or more letters at Week 8 versus baseline in the compared groups.
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a randomized, double-blind, comparative, parallel group study of the efficacy, safety pharmacokinetics, and immunogenicity of GNR-067 and Lucentis® in patients with neovascular (wet) age-related macular degeneration.
Detailed Description
Age-related macular degeneration (ARMD) is a chronic progressive disease that is the main cause of visual disability in elderly patients (aged over 60 years) in industrialized countries. Due to increased human longevity, it is expected for the number of patients with this disease to grow worldwide up to 288 million people by 2040. The highest risk of vision loss is posed by neovascular (exudative or wet ARMD) macular degeneration observed in 10-20% of cases. The pathological changes of ARMD are based on the increased production of the vascular endothelial growth factor (VEGF) which affects proprioceptors located on the surface of endothelial cells and causes an anomalous permeability of vessels and stimulates neovascularization GNR-067 (JSC "GENERIUM", the Russian Federation) is a humanized recombinant monoclonal antibody selectively binding to the human vascular endothelial growth factor \[VEGF-A\] and is a biosimilar of of the original product Lucentis® ("Novartis Pharma AG", Switzerland). This III phase study is aimed to compare the effectiveness, safety, pharmacokinetics and immunogenicity of GNR-067 (JSC "GENERIUM", the Russian Federation) and Lucentis® ("Novartis Pharma AG", Switzerland) in order to register of the drug GNR-067 (JSC "GENERIUM", the Russian Federation), a solution for intraocular injection administration, in the Russian Federation. The study included patients (n = 408) aged 50 years and older with neovascular (wet) age-related macular degeneration, types 1 and 2 (occult and classical) choroidal neovascularization (CNV) with the following activity signs: accumulation of intraretinal and/or subretinal (under the neurosensory retina or pigment epithelium) fluid, extravasal dye exit from the newly formed vessels, and the presence of a subfoveal and/or juxtafoveal membrane and the presence of CNV foci of more than 50% of the total lesion area. With block randomization, the patients were divided into two groups in a 2:1 ratio (investigational/reference product): 272 patients to the group of the investigational product GNR-067 and 136 patients to the group of the reference product Lucentis®. The duration of the study for each patient will be approximately 52 ± 4 weeks, including a screening period (3 weeks), treatment period and a follow-up period (4 weeks). In this study GNR-067 and Lucentis® will be used intravitreally once every 4 weeks (thirteen injections in total) in 0.5 mg doses (the injection volume is 0.05 mL).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women aged 50 years and older;
- •The signed informed consent obtained from the patient, or, in cases of severe visual impairment in the patient, with the participation of an impartial witness, prior to any study-related procedures.
- •Ophthalmic inclusion criteria (must be present in one eye, which will be considered the examined eye)
- •The previously diagnosed neovascular (wet) age-related macular degeneration confirmed at the Screening Visit:
- •untreated, except for food supplement, vitamins, mineral additives (one examined eye in one patient); Types 1 and 2 (occult and classical) choroidal neovascularization (CNV) with the following activity signs: accumulation of intraretinal and/or subretinal (under the neurosensory retina or pigment epithelium) fluid, extravasal dye exit from the newly formed vessels, and the presence of a subfoveal and/or juxtafoveal membrane and the presence of CNV foci of more than 50% of the total lesion area;
- •The best-corrected visual acuity within a range from 34 to 83 letters (20/200 to 20/25) measured using the ETDRS chart Early Treatment Diabetic Retinopathy Study Research Group protocol (chart at a distance of 4 m) before pupil dilation;
- •The willingness and ability of the patient to perform all planned study visits and procedures (according to the Investigator);
- •IOP ≤21 mmHg (actual);
- •An ECG within normal values or clinically insignificant findings.
Exclusion Criteria
- •Medical history of CNV treatment with intravitreal injections of VEGF inhibitors (ranibizumab, bevacizumab, aflibercept, or pegaptanib, etc.), or any other investigational poducts into the examined eye;
- •Medical history of subretinal laser photocoagulation or other surgical interventions for ARMD in any eye;
- •Preexisting and current lesions, diseases, or interventions in the eyes.:
- •In the examined eye:
- •Keratoplasty or corneal dystrophy Capsulotomy performed 4 weeks prior to screening Aphakia, vitrectomy Presence of a macular hole at any stage Past rhegmatogenous retinal detachment Any other past intraocular surgical interventions in the examined eye (including cataract extraction in the examined eye) within 3 months prior to the Screening Visit
- •In any eye:
- •Choroidal neovascularization in any eye due to reasons not related to ARMD (for example, multifocal choroiditis, ocular histoplasmosis syndrome, injury, etc.) Past idiopathic or autoimmune uveitis in any eye Scleromalacia Diagnosed diabetic retinopathy
- •Current conditions and diseases identified at the screening stage:
- •High degree myopia (over 8 diopters) in any eye; Presence of progressive glaucoma (intraocular pressure ≥21 mmHg against performed antihypertensive glaucoma therapy) or optic neuropathy that affect or endanger the central field of view in the examined eye at the screening stage; Subretinal hemorrhage and/or hemorrhage in the retinal tissue occupying ≥50% of the total affected area in the examined eye; Presence of a rupture (solution of continuity) of the retinal pigment epithelium (RPE) also extending to the macula in any eye; A scar or subretinal fibrosis in the macular area occupying more than 50% of the total affected area in any eye; Presence of vitreomacular traction or epiretinal membrane significantly affecting central vision; Other than ARMD progressive retinal diseases in the examined or fellow eye that may complicate the assessment of visual acuity; The total size of the lesion is more than 12 disc areas (DA: 30.5 mm2 including areas occupied by blood, neovascularization, or fibrosis), based on a FAG performed at screening; Confirmed or assumed (within 28 days prior to the Screening Visit) intraocular, extraocular, and periocular inflammation or infection in any eye.
- •Any intravitreal injections of corticosteroids (e.g., triamcinolone acetonide) for ≥30 days in a row in the examined eye 90 days prior to the Screening Visit and/or injection of an intravitreal corticosteroid implant with a gradual release of the medicinal product into the examined eye within 180 days prior to the Screening Visit;
Outcomes
Primary Outcomes
The proportion of patients (%) with an increase in the best-corrected visual acuity (BCVA) score on the ETDRS chart (measured using logMAR/Snellen chart) of 15 or more letters at Week 8 versus baseline in the compared groups.
Time Frame: At 8 Week after comparative treatment beginning (GNR-067 vs. Lucentis®).
Global evaluation of treatment effectiveness (the best-corrected visual acuity (BCVA) score on the ETDRS chart (measured using logMAR/Snellen chart)) of 15 or more letters are a validated tool and has been used to evaluate the clinical response to ranibizumab in patients with with neovascular (wet) age-related macular degeneration.
Secondary Outcomes
- The proportion of patients (%) with an increase in the best-corrected visual acuity (BCVA) score on the ETDRS chart (measured using logMAR/Snellen chart) of 15 or more letters at Week 24, Week 52 versus baseline in the compared groups.(At Week 24, Week 52 after comparative treatment start (GNR-067 vs. Lucentis®) and compared to baseline.)
- The proportion of patients (%) with a decrease in the best-corrected visual acuity (BCVA) score on the ETDRS chart (measured using logMAR/Snellen chart) of 15 or fewer letters at Week 8, Week 24, and Week 52 versus baseline in the compared groups.(At Week 8, Week 24, Week 52 weeks after comparative treatment start (GNR-067 vs. Lucentis®) and compared to baseline.)
- The decrease of the central retinal thickness (CRT) measured with optical coherence tomography in the spectral range at Week 8, Week 24, Week 52 versus baseline in the compared groups.(At Week 8, Week 24, Week 52 versus baseline in the compared groups.)
- The proportion of patients (%) with the presence (incomplete recovery) of intraretinal fluid and subretinal fluid at Week 8, Week 24, Week 52 versus baseline in the compared groups.(At Week 8, Week 24, Week 52 versus baseline in the compared groups)
- The assessment of changes in visual acuity and quality of life of patients by the questionnaire method using the NEI VFQ-25 medical ophthalmological questionnaire at Week 24 Week 52 versus baseline in the compared groups.(At Week 24 Week 52 versus baseline in the compared groups.)
- Immunogenicity(The frequency of formation of ADAs to ranibizumab at Day 1, Day 8, Week 8, Week 24, Week 36, and Week 52 of treatment with the investigational or reference product with the characterization of antibodies.)