Multiple Dose Safety and Efficacy of LKA651 in Patients With Diabetic Macular Edema

NCT ID: NCT03927690

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-24
• Study Completion Date: 2022-08-31

Brief Summary

The primary objectives of this study were to evaluate the safety and efficacy of LKA651 in patients with macular edema from diabetic macular edema (DME),

Detailed Description

This study was a 3-arm, parallel group, randomized, patient- and investigator-masked trial planned in 90 patients with Diabetic macular edema (DME). The study consisted of a screening period of 60 days, main study (12 weeks), and an extension period (12 weeks). The study was stratified such that sentinel safety cohorts were first enrolled to test the safety of the combination of LKA651 and Lucentis before proceeding with further patient randomization. After determination of safety from Day 15 data from each sentinel cohort, patients were enrolled into 1 of 3 arms: LKA651 monotherapy, LKA651 plus Lucentis, and Lucentis monotherapy. Every patient was dosed 3 times in 4 week intervals in the treatment phase and was then followed up for an extension phase of an additional 12 weeks during which Lucentis was allowed to be administered as rescue at the discretion of the Investigator. No predefined rescue criteria were outlined as guidance.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

LKA651

LKA651 Intravitreal injection

Group Type: EXPERIMENTAL

LKA651

Intervention Type: DRUG

LKA651 5 mg Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

LKA651 + Lucentis

LKA651 + Lucentis Intravitreal injection

Group Type: EXPERIMENTAL

LKA651

Intervention Type: DRUG

LKA651 5 mg Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

Lucentis

Intervention Type: DRUG

Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

Lucentis

Lucentis Intravitreal injection

Group Type: ACTIVE_COMPARATOR

Lucentis

Intervention Type: DRUG

Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

Interventions

LKA651

LKA651 5 mg Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

Intervention Type: DRUG

Lucentis

Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent must be obtained before any assessment is performed.
• Male and female patients age 18 to 85 years of age inclusive at screening
• Presence 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 70 letters (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 Diabetic macular edema (DME) in the study eye, with decrease in vision due to foveal thickening of central macular thickness ≥ 320 µm in the central subfield, as assessed on Spectral domain optical coherence tomography (SD-OCT) and confirmed by the central reading center at screening
• 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

Exclusion Criteria

• Patient with history of intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) treatment in the study eye <90 days from baseline
• Patient with history of intraocular corticosteroids 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
• Laser photocoagulation (macular or panretinal) in the study eye during the 3-month period prior to baseline.
• High risk proliferative diabetic retinopathy
• 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
• Area of macular retinal ischemia (as measured by the foveal avascular zone) ≥ 1000 μm.
• Active intraocular inflammation (graded as trace or above) or active intraocular infection in either eye.
• Current diagnosis of or laboratory evidence for anemia, defined as a hemoglobin <10 g/dL for women and <11 g/dL for men.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Beverly Hills, California, United States

Novartis Investigative Site

Rancho Cordova, California, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

‘Aiea, Hawaii, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Austin, Texas, United States

Novartis Investigative Site

San Antonio, Texas, United States

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Göttingen, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Arecibo, , Puerto Rico

Novartis Investigative Site

Seville, Andalusia, Spain

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, Spain

Novartis Investigative Site

Barcelona, , Spain

Novartis Investigative Site

Córdoba, , Spain

Novartis Investigative Site

Zaragoza, , Spain

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Kocaeli, , Turkey (Türkiye)

Countries

United States; Germany; Puerto Rico; Spain; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1566

Patient Lay Trial Summary

Other Identifiers

2018-000031-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLKA651X2202

Identifier Type: -

Identifier Source: org_study_id