Clinical trial NCT03927690: Multiple Dose Safety and Efficacy of LKA651 in Patients With Diabetic Macular Edema
Official title: A Randomized, Active-controlled, Patient and Investigator-masked, Multiple Dose Proof-of-concept Study of Intravitreal LKA651 in Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Macular Edema
Keywords: Macular degeneration
age-related macular degeneration (ARMD)
vision loss
macula damage
retina damage
dry macular degeneration
wet macular degeneration
AMD
diabetic macular edema
DME
neovascular age-related macular degeneration
nAMD
retinal vein occlusion
RVO
Diabetic Macular edema (DME)
macular edema
diabetic retinopathy
LKA651
Lucentis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-04-25
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
measure: Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
measure: Number of Participants With Non-ocular Adverse Events (>=2%)
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 12 weeks post treatment, up to a maximum timeframe of approximately 24 weeks (approximately 168 days).
measure: Intraocular Pressure (IOP) in Study Eye
timeFrame: Screening, and Day 85
measure: Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye
timeFrame: Days 2, 8, 15, 29, 43, 57, and 85
measure: Inner Macular Thickness (Inferior)
timeFrame: Week 12 (Day 85)
measure: Inner Macular Thickness (Temporal)
timeFrame: Week 12 (Day 85)
measure: Outer Macular Thickness (Inferior)
timeFrame: Week 12 (Day 85)
measure: Outer Macular Thickness (Temporal)
timeFrame: Week 12 (Day 85)
measure: Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye
timeFrame: Days 29, 57, 85, End of Study (Up to Day 140)
measure: Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye
timeFrame: Days 8, 15, 29, 43, 57, 85
Secondary outcomes:
measure: Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12
timeFrame: Week 12 (Day 85) up to Day 140
measure: Time to Retreatment in Study Eye With Anti-VEGF After Week 12
timeFrame: Week 12 (Day 85) up to Day 140
measure: Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651
timeFrame: Day 1 (0, 0.5 and 4 hrs post dose), Day 2, Day 8, Day 15, Day 29 (0, 0.5 and 4 hrs post dose), Day 43, Day 57 (0, 0.5 and 4 hrs post dose), Day 85
measure: Summary Statistics of Pharmacokinetics - AUC0-28d of LKA651 (Serum)
timeFrame: Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85
measure: Summary Statistics of Pharmacokinetics - Serum Concentrations of Lucentis
timeFrame: Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85
measure: Summary Statistics of Pharmacokinetics - AUC0-28d of Lucentis (Serum)
timeFrame: Day 1 - 4 hrs post dose, Day 2, Day 8, Day 15, Day 29 - 4 hrs post dose, Day 43, Day 57 - 4 hrs post dose, Day 85
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Rancho Cordova
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: 'Aiea
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Arecibo
country: Puerto Rico
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sant Cugat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: