diabetic macular edema MedDRA version: 20.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema System Organ Class: 100000004853
Conditions
Interventions
Product Name: LKA651
Product Code: LKA651
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LKA651
Current Sponsor code: LKA651
Other descriptive name: LKA651
Concentration unit: mg/ml
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male and female patients age 18 to 90 years of age inclusive • Diagnosis of type I or type II diabetes mellitus. • The Early Treatment Diabetic Retinopathy Study (ETDRS) letter score in the study eye must be between 24 and 72 letters inclusive (approximate Snellen equivalent of 20/40-20/320). The non-study eye (fellow eye) should be =34 letters or better (approximate Snellen equivalent of 20/200) at screening • Presence of DME in the study eye, with decrease in vision due to foveal thickening of central macular thickness = 320µm in the central subfield, as assessed on spectral-domain ocular coherence tomography (SD-OCT) and confirmed by the central reading center at screeening • Sufficiently clear ocular media and adequate pupil dilation in the study eye to permit fundus photographs of adequate clarity to measure diameters of retinal arteries and veins at screening Please refer to the protocol for a comprehensive list of inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: Patient with history of treatment for DME in the study eye as defined by the following: - IVT anti-vascular endothelial growth factor (VEGF) treatment within 90 days before baseline in the study eye. History or concurrent treatment with these medications/procedures in the non study eye is permitted. - Patient with history of intraocular corticosteroids in the study eye including dexamethasone intravitreal implants during the 6 month period prior to baseline. Any prior use of fluocinolone acetonide intravitreal implant (Iluvien) is prohibited regardless of timing. • Concomitant conditions or ocular disorders in the study eye which may, in the opinion of the investigator, confound the interpretation of study results, compromise visual acuity or require medical or surgical intervention during the study period: - High risk proliferative diabetic retinopathy in the study eye, as per investigator assessment at both screening and baseline. - Patients with the following conditions in the study eye at screening or baseline must be excluded: structural damage of the fovea, vitreous hemorrhage, retinal detachment, vitreomacular traction, macular hole, retinal vein/arterial occlusion, neovascularization of iris or choroidal neovascularization of any cause) 3. Laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline. • Patients, with type 1 or type 2 diabetes who have a hemoglobin A1C = 12% at screening. • Any progressive disease of the retina in the study eye (e.g. uveitis, rod-cone dystrophy) or optic nerve other than those listed in the inclusion criteria. • Area of retinal ischemia involving the macula (as measured by the foveal avascular zone) = 1000 µm in linear diameter. • Active intraocular inflammation (graded as trace or above) in either eye or active intraocular infection in the study eye. • Active infection involving the study eye's ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye, or intraocular infection in either eye. • Any intraocular surgery (except uncomplicated cataract surgery) in the study eye within the past 6 months preceding Day 1. Uncomplicated cataract surgery (e.g. routine surgery with no intra or post operative complications) within the past 3 months preceding Day 1. Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within the past 30 days preceding baseline. • Current diagnosis of clinically significant anemia, or hemoglobin <10 g/dL for women and <11 g/dL for men. Please refer to the protocol for a comprehensive list of exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, tolerability, and efficacy, in reference to Lucentis® monotherapy, of three q4w intravitreal (IVT) doses of LKA651 in treating DME when administered as monotherapy and in combination with Lucentis® ;Secondary Objective: - To evaluate the serum pharmacokinetic (PK) profile of total LKA651 and Lucentis® following three q4w IVT doses of LKA651, or a combination of LKA651 and Lucentis,® in patients with DME - To evaluate duration of effect of three q4w IVT doses of LKA651 in patients with DME. - To evaluate the effect of IVT LKA651 on diabetic retinopathy (DR) progression in patients with DME. ;Primary end point(s): 1) Best Corrected Visual Acuity (BCVA) as assessed by ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity charts at week 12. 2) Central subfield retinal thickness as measured by SD-OCT at week 12 3) Ocular and systemic AEs - are evaluated on 1,15,43,85,113,141 and 169 days. 4) Vital signs are evaluated on blood pressure and heart rate -1,29,57,85,113,141 and 169 days ECG intervals - 1 and 169 days 5) Safety laboratory measures (including reticulocyte count) are evaluated on 1,29,57,85 and 169 days 6) Complete ophthalmic exam is evaluated on : • IOP - 1,29,57,85,113,141 and 169 days • BCVA - 1,29,57,85,113,141 and 169 days • Macular thickness by SD-OCT - 1,29,57,85,113,141 and 169 days • FA - 85 and 169 days;Timepoint(s) of evaluation of this end point: 1) Best Corrected Visual Acuity as assessed by ETDRS visual acuity charts - week 12. 2) Central subfield retinal thickness as measured by SD-OCT - week 12 3 )Ocular and systemic AEs - are evaluated on 1,15,43,85,113,141 and 169 days 4) Vital signs are evaluated on blood pressure and heart rate -1,29,57,85,113,141 and 169 days ECG intervals - 1 and 169 5) Safety laboratory measures (including reticulocyte count) are evaluated on 1,29,57,85 and 169 6) Complet | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Time to retreatment with anti-VEGF (as determined by PI) after week 12 during an additional 12-week extension phase 2) Serum levels of total LKA651 (Maximum concentration (Cmax) and Area under the curve (AUC)0-28d in monotherapy or in combination with Lucentis® after the first dose 3) Serum levels of ranibizumab (Cmax and AUC0-28d) when administered in combination with LKA651 after the first dose 4) Patients with 2 and =3 step improvement in the diabetic retinopathy severity scale by color fundus photos at week 12 and week 24 ;Timepoint(s) of evaluation of this end point: to 1) Time to retreatment with anti-VEGF (as determined by PI) after week 12 during an additional 12-week extension phase - week 12 and week 24 2) Serum levels of total LKA651 (Maximum concentration (Cmax) and Area under the curve (AUC)0-28d in monotherapy or in combination with Lucentis® after the first dose - day 29 3) Serum levels of ranibizumab (Cmax and AUC0-28d) when administered in combination with LKA651 after the first dose - day 29 4) Patients with 2 and =3 step improvement in the diabetic retinopathy severity scale by color fundus photos - week 12 and week 24 | — |
Countries
Germany, Spain, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed