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

NCT03927690 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLKA651X22022018-000031-28
• Study Type: interventional
• Target: 91
• Locations: 5 countries
• Sites: 22

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),

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

Outcome Measures

Primary Outcomes (11)

• 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.

  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).

• 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.

  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).

• 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.

  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).

• Intraocular Pressure (IOP) in Study Eye

  Intraocular pressure was measured per the study site's regular practice.

  Screening, and Day 85

• 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.

  Days 2, 8, 15, 29, 43, 57, and 85

• Inner Macular Thickness (Inferior)

  Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

  Week 12 (Day 85)

• Inner Macular Thickness (Temporal)

  Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

  Week 12 (Day 85)

• Outer Macular Thickness (Inferior)

  Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

  Week 12 (Day 85)

• Outer Macular Thickness (Temporal)

  Macular thickness was measured by spectral domain optical coherence tomography (SD-OCT).

  Week 12 (Day 85)

• 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).

  Days 29, 57, 85, End of Study (Up to Day 140)

• 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.

  Days 8, 15, 29, 43, 57, 85

Secondary Outcomes (6)

• 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 - 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 - 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 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

Study Arms (3)

LKA651

EXPERIMENTAL

LKA651 Intravitreal injection

Drug: LKA651

LKA651 + Lucentis

EXPERIMENTAL

LKA651 + Lucentis Intravitreal injection

Drug: LKA651; Drug: Lucentis

Lucentis

ACTIVE COMPARATOR

Lucentis Intravitreal injection

Drug: Lucentis

Interventions

LKA651 DRUG

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

LKA651; LKA651 + Lucentis

Lucentis 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

LKA651 + Lucentis; Lucentis

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (22)

Novartis Investigative Site

Beverly Hills, California, 90211, United States

Location

Novartis Investigative Site

Rancho Cordova, California, 95670, United States

Location

Novartis Investigative Site

Miami, Florida, 33143, United States

Location

Novartis Investigative Site

‘Aiea, Hawaii, 96701, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02118, United States

Location

Novartis Investigative Site

Austin, Texas, 78750, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78240, United States

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Münster, 48145, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Arecibo, 00612, Puerto Rico

Location

Novartis Investigative Site

Seville, Andalusia, 41009, Spain

Location

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, 08190, Spain

Location

Novartis Investigative Site

Barcelona, 08025, Spain

Location

Novartis Investigative Site

Córdoba, 14012, Spain

Location

Novartis Investigative Site

Zaragoza, 50009, Spain

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06490, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06500, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Macular Degeneration; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration; Retinal Vein Occlusion; Macular Edema; Diabetic Retinopathy

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2019
• First Posted: April 25, 2019
• Study Start: May 24, 2019
• Primary Completion: June 17, 2022
• Study Completion: August 31, 2022
• Last Updated: June 20, 2024
• Results First Posted: October 12, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); TU (4); US (7); ES (5); PR (1)