Diabetic Macular Edema
Conditions
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
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.
Interventions
DRUGLucentis
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
DRUGLKA651
LKA651 5 mg Intravitreal injection, every 4 weeks for 12 weeks in the treatment phase
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Days 8, 15, 29, 43, 57, 85 | Central subfield thickness was measured by spectral domain optical coherence tomography (SD-OCT). Central subfield retinal thickness was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Log-transformed baseline central subfield retinal thickness and treatment naïve and treatment experienced variable were used as covariates. Results were back-transformed to show results as a ratio to baseline. |
| Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Days 2, 8, 15, 29, 43, 57, and 85 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. BCVA in study eye was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Baseline BCVA value and treatment naïve and treatment experienced variable were used as covariates. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. |
| Inner Macular Thickness (Inferior) | Week 12 (Day 85) | Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT). |
| Inner Macular Thickness (Temporal) | Week 12 (Day 85) | Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT). |
| Outer Macular Thickness (Inferior) | Week 12 (Day 85) | Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT). |
| Outer Macular Thickness (Temporal) | Week 12 (Day 85) | Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT). |
| Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Days 29, 57, 85, End of Study (Up to Day 140) | Foveal avascular zone was assessed by fluorescein angiography (FA). |
| Number of Participants With Adverse Events | 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). | An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient. The severity of the AEs (mild, moderate, severe) was based on the Common Terminology Criteria for Adverse Events (CTCAE). Number of participants in each category is reported in the table. A participant who falls multiple times in one category is counted only once. |
| Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | 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). | An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient. |
| Number of Participants With Non-ocular Adverse Events (>=2%) | 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). | An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient. |
| Intraocular Pressure (IOP) in Study Eye | Screening, and Day 85 | Intraocular pressure was measured per the study site's regular practice. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Retreatment in Study Eye With Anti-VEGF After Week 12 | Week 12 (Day 85) up to Day 140 | Time to retreatment with anti VEGF (as determined by the investigator) after Week 12 during the additional 12 week extension phase (that was up to 16 weeks after the last dose) was examined with a Kaplan Meier plot. |
| Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | 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 | PK parameters were determined using non-compartmental methods using the most recent version of WinNonlin Phoenix (Version 8.2). Concentrations below the lower limit of quantification (LLOQ) were treated as 1/2 LLOQ in summary statistics. |
| Summary Statistics of Pharmacokinetics - AUC0-28d of LKA651 (Serum) | 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 | Area under the curve over the dosing interval 0 to 28 days. |
| Summary Statistics of Pharmacokinetics - Serum Concentrations of Lucentis | 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 | — |
| Summary Statistics of Pharmacokinetics - AUC0-28d of Lucentis (Serum) | 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 | Area under the curve over the dosing interval 0 to 28 days. |
| Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12 | Week 12 (Day 85) up to Day 140 | — |
Countries
Germany, Puerto Rico, Spain, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
The study population consisted of male and female patients with DME, who were 18 to 85 years of age at screening, and who were either treatment naive or experienced i.e. had been treated with anti VEGF therapy \> 90 days before baseline.
Participants by arm
| Arm | Count |
|---|---|
| LKA651 LKA651 5 mg Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase | 28 |
| LKA651 + Lucentis LKA651 1 mg + Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase | 30 |
| Lucentis Lucentis 0.3 mg (U.S. sites) or 0.5 mg (ex U.S. sites) Intravitreal injection, every 4 weeks for a total of 3 doses in the treatment phase | 33 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | LKA651 + Lucentis | Lucentis | Total | LKA651 |
|---|---|---|---|---|
| Age, Continuous | 63.8 Years STANDARD_DEVIATION 8.18 | 61.2 Years STANDARD_DEVIATION 9.02 | 62.2 Years STANDARD_DEVIATION 8.6 | 61.6 Years STANDARD_DEVIATION 8.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 32 Participants | 82 Participants | 23 Participants |
| Sex: Female, Male Female | 13 Participants | 10 Participants | 32 Participants | 9 Participants |
| Sex: Female, Male Male | 17 Participants | 23 Participants | 59 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 0 / 30 | 0 / 33 | 1 / 91 |
| other Total, other adverse events | 20 / 28 | 16 / 30 | 19 / 33 | 55 / 91 |
| serious Total, serious adverse events | 3 / 28 | 4 / 30 | 1 / 33 | 8 / 91 |
Outcome results
Primary
Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual function of the study eye was assessed using the ETDRS protocol. BCVA in study eye was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Baseline BCVA value and treatment naïve and treatment experienced variable were used as covariates. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Time frame: Days 2, 8, 15, 29, 43, 57, and 85
Population: Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 8 | 65.2 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 43 | 67.8 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 29 | 65.5 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 2 | 61.5 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 85 | 67.8 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 57 | 67.6 Scores on a scale |
| LKA651 | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 15 | 65.9 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 29 | 68.2 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 2 | 64.4 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 8 | 68.6 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 15 | 68.6 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 43 | 70.4 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 57 | 71.5 Scores on a scale |
| LKA651 + Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 85 | 72.5 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 43 | 69.1 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 8 | 66.2 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 85 | 70.5 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 57 | 70.0 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 29 | 68.5 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 15 | 68.4 Scores on a scale |
| Lucentis | Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye | Day 2 | 64.1 Scores on a scale |
Comparison: Day 2p-value: 0.88790% CI: [-6.2, 1]Mixed model repeated measures analysis
Comparison: Day 2p-value: 0.43190% CI: [-2.6, 3.2]Mixed model repeated measures analysis
Comparison: Day 8p-value: 0.64790% CI: [-5.4, 3.4]Mixed model repeated measures analysis
Comparison: Day 8p-value: 0.1390% CI: [-1.1, 6]Mixed model repeated measures analysis
Comparison: Day 15p-value: 0.81890% CI: [-6.9, 2]Mixed model repeated measures analysis
Comparison: Day 15p-value: 0.45790% CI: [-3.6, 4.1]Mixed model repeated measures analysis
Comparison: Day 29p-value: 0.90690% CI: [-6.9, 0.8]Mixed model repeated measures analysis
Comparison: Day 29p-value: 0.56690% CI: [-4.1, 3.3]Mixed model repeated measures analysis
Comparison: Day 43p-value: 0.68690% CI: [-5.6, 3.1]Mixed model repeated measures analysis
Comparison: Day 43p-value: 0.2890% CI: [-2.5, 5.2]Mixed model repeated measures analysis
Comparison: Day 57p-value: 0.84990% CI: [-6.3, 1.4]Mixed model repeated measures analysis
Comparison: Day 57p-value: 0.25490% CI: [-2.2, 5.2]Mixed model repeated measures analysis
Comparison: Day 85p-value: 0.86690% CI: [-6.6, 1.3]Mixed model repeated measures analysis
Comparison: Day 85p-value: 0.19890% CI: [-1.9, 5.8]Mixed model repeated measures analysis
Primary
Inner Macular Thickness (Inferior)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Time frame: Week 12 (Day 85)
Population: Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LKA651 | Inner Macular Thickness (Inferior) | 503.06 micrometer | Standard Deviation 137.235 |
| LKA651 + Lucentis | Inner Macular Thickness (Inferior) | 400.82 micrometer | Standard Deviation 53.18 |
| Lucentis | Inner Macular Thickness (Inferior) | 390.48 micrometer | Standard Deviation 48.097 |
Primary
Inner Macular Thickness (Temporal)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Time frame: Week 12 (Day 85)
Population: Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LKA651 | Inner Macular Thickness (Temporal) | 505.27 micrometer | Standard Deviation 141.41 |
| LKA651 + Lucentis | Inner Macular Thickness (Temporal) | 414.64 micrometer | Standard Deviation 67.032 |
| Lucentis | Inner Macular Thickness (Temporal) | 404.93 micrometer | Standard Deviation 56.099 |
Primary
Intraocular Pressure (IOP) in Study Eye
Intraocular pressure was measured per the study site's regular practice.
Time frame: Screening, and Day 85
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LKA651 | Intraocular Pressure (IOP) in Study Eye | Screening | 15.1 mmHg | Standard Deviation 3.2 |
| LKA651 | Intraocular Pressure (IOP) in Study Eye | Day 85 | 15.5 mmHg | Standard Deviation 3.56 |
| LKA651 + Lucentis | Intraocular Pressure (IOP) in Study Eye | Screening | 14.9 mmHg | Standard Deviation 3.44 |
| LKA651 + Lucentis | Intraocular Pressure (IOP) in Study Eye | Day 85 | 15.6 mmHg | Standard Deviation 3.67 |
| Lucentis | Intraocular Pressure (IOP) in Study Eye | Screening | 15.5 mmHg | Standard Deviation 2.88 |
| Lucentis | Intraocular Pressure (IOP) in Study Eye | Day 85 | 15.2 mmHg | Standard Deviation 3.79 |
Primary
Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye
Central subfield thickness was measured by spectral domain optical coherence tomography (SD-OCT). Central subfield retinal thickness was analyzed with a mixed model for repeated measures. The model included treatment, visit, and the treatment by visit interaction as independent variables. An unstructured residual covariance structure was used. Log-transformed baseline central subfield retinal thickness and treatment naïve and treatment experienced variable were used as covariates. Results were back-transformed to show results as a ratio to baseline.
Time frame: Days 8, 15, 29, 43, 57, 85
Population: Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 8 | 0.99 ratio |
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 15 | 0.97 ratio |
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 29 | 1.00 ratio |
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 43 | 1.04 ratio |
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 57 | 0.95 ratio |
| LKA651 | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 85 | 0.97 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 85 | 0.75 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 8 | 0.83 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 43 | 0.76 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 57 | 0.75 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 15 | 0.83 ratio |
| LKA651 + Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 29 | 0.80 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 15 | 0.80 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 29 | 0.82 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 85 | 0.78 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 43 | 0.79 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 8 | 0.83 ratio |
| Lucentis | Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye | Day 57 | 0.80 ratio |
Comparison: Day 43p-value: 190% CI: [1.2, 1.46]Mixed model repeated measures analysis
Comparison: Day 8p-value: 0.99890% CI: [1.08, 1.33]Mixed model repeated measures analysis
Comparison: Day 8p-value: 0.52790% CI: [0.92, 1.09]Mixed model repeated measures analysis
Comparison: Day 15p-value: 0.99990% CI: [1.1, 1.33]Mixed model repeated measures analysis
Comparison: Day 15p-value: 0.71690% CI: [0.95, 1.12]Mixed model repeated measures analysis
Comparison: Day 29p-value: 190% CI: [1.13, 1.31]Mixed model repeated measures analysis
Comparison: Day 29p-value: 0.28190% CI: [0.91, 1.05]Mixed model repeated measures analysis
Comparison: Day 43p-value: 0.290% CI: [0.88, 1.04]Mixed model repeated measures analysis
Comparison: Day 57p-value: 190% CI: [1.09, 1.28]Mixed model repeated measures analysis
Comparison: Day 57p-value: 0.08390% CI: [0.87, 1.01]Mixed model repeated measures analysis
Comparison: Day 85p-value: 190% CI: [1.14, 1.38]Mixed model repeated measures analysis
Comparison: Day 85p-value: 0.25490% CI: [0.88, 1.06]Mixed model repeated measures analysis
Primary
Number of Participants With Adverse Events
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient. The severity of the AEs (mild, moderate, severe) was based on the Common Terminology Criteria for Adverse Events (CTCAE). Number of participants in each category is reported in the table. A participant who falls multiple times in one category is counted only once.
Time frame: 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).
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LKA651 | Number of Participants With Adverse Events | AEs of severe intensity | 4 Participants |
| LKA651 | Number of Participants With Adverse Events | Non-serious AEs | 20 Participants |
| LKA651 | Number of Participants With Adverse Events | Serious AEs | 3 Participants |
| LKA651 | Number of Participants With Adverse Events | Study drug-related AEs | 2 Participants |
| LKA651 | Number of Participants With Adverse Events | AEs of mild intensity | 16 Participants |
| LKA651 | Number of Participants With Adverse Events | AEs, Patients with AEs | 20 Participants |
| LKA651 | Number of Participants With Adverse Events | Study-drug related AEs leading to discontinuation of study treatment | 1 Participants |
| LKA651 | Number of Participants With Adverse Events | AEs of moderate intensity | 8 Participants |
| LKA651 | Number of Participants With Adverse Events | AEs leading to discontinuation of study treatment | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | AEs of moderate intensity | 6 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | AEs, Patients with AEs | 16 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | AEs of mild intensity | 15 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | AEs of severe intensity | 2 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | Study drug-related AEs | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | Serious AEs | 4 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | Study-drug related AEs leading to discontinuation of study treatment | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Adverse Events | Non-serious AEs | 16 Participants |
| Lucentis | Number of Participants With Adverse Events | AEs of moderate intensity | 3 Participants |
| Lucentis | Number of Participants With Adverse Events | AEs, Patients with AEs | 19 Participants |
| Lucentis | Number of Participants With Adverse Events | AEs leading to discontinuation of study treatment | 0 Participants |
| Lucentis | Number of Participants With Adverse Events | AEs of mild intensity | 19 Participants |
| Lucentis | Number of Participants With Adverse Events | Non-serious AEs | 19 Participants |
| Lucentis | Number of Participants With Adverse Events | Study drug-related AEs | 2 Participants |
| Lucentis | Number of Participants With Adverse Events | AEs of severe intensity | 1 Participants |
| Lucentis | Number of Participants With Adverse Events | Study-drug related AEs leading to discontinuation of study treatment | 0 Participants |
| Lucentis | Number of Participants With Adverse Events | Serious AEs | 1 Participants |
Primary
Number of Participants With Non-ocular Adverse Events (>=2%)
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient.
Time frame: 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).
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LKA651 | Number of Participants With Non-ocular Adverse Events (>=2%) | 16 Participants |
| LKA651 + Lucentis | Number of Participants With Non-ocular Adverse Events (>=2%) | 15 Participants |
| Lucentis | Number of Participants With Non-ocular Adverse Events (>=2%) | 14 Participants |
Primary
Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation patient.
Time frame: 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).
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Lenticular opacities | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Ocular hypertension | 2 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinopathy | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eyelids pruritus | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Abnormal sensation in eye | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreoretinal traction syndrome | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eye pain | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Anterior chamber flare | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal detachment | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dacryostenosis acquired | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Corneal erosion | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Visual acuity reduced | 3 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Cystoid macular oedema | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal haemorrhage | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal cyst | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreous haemorrhage | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinal oedema | 2 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Patients with at least one ocular AE in study eye | 11 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dry eye | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Conjunctival haemorrhage | 1 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Punctate keratitis | 0 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Macular oedema | 2 Participants |
| LKA651 | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal exudates | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Punctate keratitis | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Patients with at least one ocular AE in study eye | 7 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Conjunctival haemorrhage | 4 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinal oedema | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinopathy | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Visual acuity reduced | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreous haemorrhage | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dry eye | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Macular oedema | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Ocular hypertension | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Abnormal sensation in eye | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Anterior chamber flare | 1 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Corneal erosion | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Cystoid macular oedema | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dacryostenosis acquired | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eye pain | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eyelids pruritus | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Lenticular opacities | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal cyst | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal detachment | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal exudates | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal haemorrhage | 0 Participants |
| LKA651 + Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreoretinal traction syndrome | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal exudates | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eyelids pruritus | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Macular oedema | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Conjunctival haemorrhage | 2 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Lenticular opacities | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dry eye | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreous haemorrhage | 2 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Punctate keratitis | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Visual acuity reduced | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Vitreoretinal traction syndrome | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal cyst | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinopathy | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal haemorrhage | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Corneal erosion | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Retinal detachment | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Cystoid macular oedema | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Anterior chamber flare | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Diabetic retinal oedema | 2 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Dacryostenosis acquired | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Abnormal sensation in eye | 1 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Patients with at least one ocular AE in study eye | 9 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Eye pain | 0 Participants |
| Lucentis | Number of Participants With Ocular Adverse Events by Preferred Term in Study Eye | Ocular hypertension | 0 Participants |
Primary
Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye
Foveal avascular zone was assessed by fluorescein angiography (FA).
Time frame: Days 29, 57, 85, End of Study (Up to Day 140)
Population: Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LKA651 | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 57 - NO CHANGE | 3 Participants |
| LKA651 | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 29 - NO CHANGE | 3 Participants |
| LKA651 | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 85 - NO CHANGE | 21 Participants |
| LKA651 | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | End of Study (Up to Day 140) - NO CHANGE | 17 Participants |
| LKA651 + Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | End of Study (Up to Day 140) - CANNOT GRADE | 1 Participants |
| LKA651 + Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 29 - NO CHANGE | 16 Participants |
| LKA651 + Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 57 - NO CHANGE | 16 Participants |
| LKA651 + Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 85 - NO CHANGE | 25 Participants |
| LKA651 + Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | End of Study (Up to Day 140) - NO CHANGE | 22 Participants |
| Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 29 - NO CHANGE | 11 Participants |
| Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 57 - NO CHANGE | 7 Participants |
| Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | End of Study (Up to Day 140) - NO CHANGE | 30 Participants |
| Lucentis | Number of Participants Without Changes in Foveal Avascular Zone as Measured by Fluorescein Angiography (FA) in Study Eye | Day 85 - NO CHANGE | 29 Participants |
Primary
Outer Macular Thickness (Inferior)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Time frame: Week 12 (Day 85)
Population: Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LKA651 | Outer Macular Thickness (Inferior) | 388.66 micrometer | Standard Deviation 88.128 |
| LKA651 + Lucentis | Outer Macular Thickness (Inferior) | 349.39 micrometer | Standard Deviation 44.538 |
| Lucentis | Outer Macular Thickness (Inferior) | 342.88 micrometer | Standard Deviation 50.612 |
Primary
Outer Macular Thickness (Temporal)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Time frame: Week 12 (Day 85)
Population: Safety analysis set - Participants in the safety analysis set with a valid measurement for the outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LKA651 | Outer Macular Thickness (Temporal) | 404.60 micrometer | Standard Deviation 103.616 |
| LKA651 + Lucentis | Outer Macular Thickness (Temporal) | 371.83 micrometer | Standard Deviation 70.124 |
| Lucentis | Outer Macular Thickness (Temporal) | 352.24 micrometer | Standard Deviation 56.793 |
Secondary
Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12
Time frame: Week 12 (Day 85) up to Day 140
Population: Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LKA651 | Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12 | 16 Participants |
| LKA651 + Lucentis | Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12 | 16 Participants |
| Lucentis | Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12 | 21 Participants |
Secondary
Summary Statistics of Pharmacokinetics - AUC0-28d of LKA651 (Serum)
Area under the curve over the dosing interval 0 to 28 days.
Time frame: 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
Population: Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of LKA651 concentrations above the lower limit of quantification.
Secondary
Summary Statistics of Pharmacokinetics - AUC0-28d of Lucentis (Serum)
Area under the curve over the dosing interval 0 to 28 days.
Time frame: 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
Population: Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of Lucentis concentrations above the lower limit of quantification.
Secondary
Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651
PK parameters were determined using non-compartmental methods using the most recent version of WinNonlin Phoenix (Version 8.2). Concentrations below the lower limit of quantification (LLOQ) were treated as 1/2 LLOQ in summary statistics.
Time frame: 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
Population: Pharmacokinetic analysis set. Concentrations below the Lower Limit of Quantification (LLOQ) are reported as zero.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 2 | 36.3 ng/mL | Standard Deviation 29.2 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 29 - 0.5 hrs post dose | 0.00 ng/mL | — |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 8 | 16.2 ng/mL | Standard Deviation 27.5 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 43 | 0.00 ng/mL | — |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 4 hrs post dose | 114 ng/mL | Standard Deviation 211 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 57 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 15 | 7.24 ng/mL | Standard Deviation 16.2 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 57 - 0.5 hrs post dos | 0.00 ng/mL | — |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 0.5 hrs post dose | 0.00 ng/mL | — |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 85 | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 29 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 57 - 4 hrs post dose | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 57 - 0.5 hrs post dos | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 85 | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 0.5 hrs post dose | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 1 - 4 hrs post dose | 4.43 ng/mL | Standard Deviation 17.1 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 2 | 8.13 ng/mL | Standard Deviation 21.6 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 8 | 2.08 ng/mL | Standard Deviation 8.06 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 15 | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 29 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 29 - 0.5 hrs post dose | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 29 - 4 hrs post dose | 7.60 ng/mL | Standard Deviation 18.6 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 43 | 0.00 ng/mL | Standard Deviation 0 |
| LKA651 + Lucentis | Summary Statistics of Pharmacokinetics - Serum Concentrations of LKA651 | Day 57 - 0 hrs | 0.00 ng/mL | Standard Deviation 0 |
Secondary
Summary Statistics of Pharmacokinetics - Serum Concentrations of Lucentis
Time frame: 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
Population: Pharmacokinetic analysis set. PK parameters could not be derived due to the limited number of Lucentis concentrations above the lower limit of quantification.
Secondary
Time to Retreatment in Study Eye With Anti-VEGF After Week 12
Time to retreatment with anti VEGF (as determined by the investigator) after Week 12 during the additional 12 week extension phase (that was up to 16 weeks after the last dose) was examined with a Kaplan Meier plot.
Time frame: Week 12 (Day 85) up to Day 140
Population: Pharmacodynamic analysis set - Participants with a valid measure and without a protocol deviation that would have an impact on the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LKA651 | Time to Retreatment in Study Eye With Anti-VEGF After Week 12 | 55.0 Days after Day 85 (Week 12) |
| LKA651 + Lucentis | Time to Retreatment in Study Eye With Anti-VEGF After Week 12 | 34.0 Days after Day 85 (Week 12) |
| Lucentis | Time to Retreatment in Study Eye With Anti-VEGF After Week 12 | 31.0 Days after Day 85 (Week 12) |
Post Hoc
All Collected Deaths
On-treatment deaths 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). Post-treatment deaths are reported for the timeframe of greater than 30 days after last treatment, until study completion, up to approximately 168 days. All deaths refer to the sum of on-treatment and post-treatment deaths.
Time frame: On-treatment - up to 12 weeks; Post-treatment - greater than 30 days after last treatment, until study completion, up to approximately 168 days
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LKA651 | All Collected Deaths | Post-Treatment Deaths | 1 Participants |
| LKA651 | All Collected Deaths | On-Treatment Deaths | 0 Participants |
| LKA651 | All Collected Deaths | All Deaths | 1 Participants |
| LKA651 + Lucentis | All Collected Deaths | Post-Treatment Deaths | 0 Participants |
| LKA651 + Lucentis | All Collected Deaths | On-Treatment Deaths | 0 Participants |
| LKA651 + Lucentis | All Collected Deaths | All Deaths | 0 Participants |
| Lucentis | All Collected Deaths | On-Treatment Deaths | 0 Participants |
| Lucentis | All Collected Deaths | All Deaths | 0 Participants |
| Lucentis | All Collected Deaths | Post-Treatment Deaths | 0 Participants |