A Randomized, Active-controlled, Patient and Investigator-masked, Multiple Dose Proof-of-concept Study of Intravitreal LKA651 in Patients With Diabetic Macular Edema
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
LKA651
LKA651 Intravitreal injection
Intervention: LKA651 (Drug)
LKA651 + Lucentis
LKA651 + Lucentis Intravitreal injection
Intervention: Lucentis (Drug)
Lucentis
Lucentis Intravitreal injection
Intervention: Lucentis (Drug)
LKA651 + Lucentis
LKA651 + Lucentis Intravitreal injection
Intervention: LKA651 (Drug)
Outcomes
Primary Outcomes
Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Charts in Study Eye
Time Frame: 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)
Time Frame: Week 12 (Day 85)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Outer Macular Thickness (Inferior)
Time Frame: Week 12 (Day 85)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Mixed Model Repeated Measures Analysis of Ratio to Baseline in Central Subfield Retinal Thickness (CSFT) in the Study Eye
Time Frame: 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.
Number of Participants With Adverse Events
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).
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
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).
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%)
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).
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
Time Frame: Screening, and Day 85
Intraocular pressure was measured per the study site's regular practice.
Inner Macular Thickness (Temporal)
Time Frame: Week 12 (Day 85)
Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).
Outer Macular Thickness (Temporal)
Time Frame: 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
Time Frame: Days 29, 57, 85, End of Study (Up to Day 140)
Foveal avascular zone was assessed by fluorescein angiography (FA).
Secondary Outcomes
- Number of Participants Who Needed Retreatment With Anti-VEGF in Study Eye After Week 12(Week 12 (Day 85) up to Day 140)
- Time to Retreatment in Study Eye With Anti-VEGF After Week 12(Week 12 (Day 85) up to Day 140)
- 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)
- 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)
- 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)