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A Study of the Safety and Tolerability of Intravitreal LKA651 in Patients With Diabetic Macular Edema

This study has been withdrawn prior to enrollment.
(Management Decision)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02281292
First Posted: November 3, 2014
Last Update Posted: December 11, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Novartis Institutes for BioMedical Research
Information provided by (Responsible Party):
Alcon Research
  Purpose
The purpose of this study is to evaluate the initial safety of intravitreal (IVT) LKA651 and potential for use alone or in combination with Ranibizumab ophthalmic solution (Lucentis®) for the treatment of Diabetic Macular Edema (DME) in patients with symptomatic disease.

Condition Intervention Phase
Diabetic Macular Edema Biological: LKA651 ophthalmic solution Biological: Ranibizumab ophthalmic solution Biological: Sham injection Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Sham Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of Intravitreal LKA651 in Patients With Diabetic Macular Edema

Resource links provided by NLM:


Further study details as provided by Alcon Research:

Primary Outcome Measures:
  • Number of subjects with a serious adverse event (SAE) that, in the opinion of the investigator, is related to the study drug [ Time Frame: Up to Day 85 ]
  • Number of subjects experiencing a non-serious adverse event [ Time Frame: Up to Day 85 ]

Secondary Outcome Measures:
  • The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass x time / volume] (AUC(0-tlast)) [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels

  • The area under the serum concentration-time curve from time zero to time 't' where t is a defined time point after administration [mass x time / volume] (AUC (0-t)) [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels

  • The observed maximum serum concentration following drug administration [mass / volume] (Cmax) [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels

  • The time to reach the maximum serum concentration after drug administration [time] (Tmax) [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels

  • The dose normalized observed maximum serum concentration following drug administration [mass*dose / volume] (Cmax/D) [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels

  • The dose-normalized area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass*dose x time / volume] (AUC/D) [ Time Frame: Up to Day 85 ]
  • Central subfield thickness [ Time Frame: Up to Day 85 ]
    Contingent upon observed serum concentration levels


Enrollment: 0
Study Start Date: December 2015
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LKA651 (Part 1)
LKA651 ophthalmic solution in 1 of 5 concentrations, administered as a single IVT injection in the study eye
Biological: LKA651 ophthalmic solution
Placebo Comparator: Sham injection (Part 1)
Sham injection in the study eye
Biological: Sham injection
Mock injection administered as an empty hub without needle
Experimental: LKA651 and Lucentis (Part 2)
LKA651 ophthalmic solution in 1 of 3 concentrations, administered as a single IVT injection in the study eye, followed by ranibizumab ophthalmic solution, 0.5 mg injection in the same eye 30 minutes later
Biological: LKA651 ophthalmic solution Biological: Ranibizumab ophthalmic solution
Other Name: Lucentis®
Placebo Comparator: Sham injection and Lucentis (Part 2)
Sham injection in the study eye, followed by ranibizumab ophthalmic solution, 0.5 mg injection in the same eye 30 minutes later
Biological: Ranibizumab ophthalmic solution
Other Name: Lucentis®
Biological: Sham injection
Mock injection administered as an empty hub without needle

Detailed Description:

This first-in-human study will be conducted in 2 parts. Part 1 is an ascending dose design to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of various single IVT doses of LKA651 in up to 48 subjects with diabetic macular edema. Subjects will be randomized to receive active or sham injections in a 3:1 ratio. A total of 6 cohorts (8 subjects per cohort) may be enrolled in Part 1. Each subject will participate in a screening/eligibility period (up to 60 days), a treatment period (single day), and an 84 day follow up period. A total of up to 11 visits will take place, all on an out-patient basis. An independent data monitoring committee (DMC) will be chartered to review cumulative safety data and approve each dose escalation and cohort progression in this first-in-human trial.

Part 2 is a double-masked design to assess the safety/tolerability, pharmacokinetics and pharmacodynamics of a single IVT dose of LKA651 when co-administered with Lucentis®. A total of up to 3 cohorts (8 subjects per cohort) may be enrolled in Part 2. Each subject will participate in a screening/eligibility period (up to 60 days), a treatment period (combination therapy, single day), and an 84 day follow up period. A total of up to 11 visits will take place, all on an out-patient basis. For the LKA651 vs sham injections, the unmasked ophthalmologist is not permitted to do any of the assessments except for the injection (and an inspection of the injection site immediately following). All other ocular assessments after randomization will be conducted by a second ophthalmologist masked to the type of injection (active or sham). The Lucentis injection (Part 2) is given open label to all patients following either the LKA651 or sham injection.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent must be obtained.
  • Type 1 or type 2 diabetes that is actively managed by a physician and hemoglobin A1C ≤ 12% at screening/eligibility.
  • Negative pregnancy test results at screening/eligibility and pre-injection on treatment day.
  • Diabetic macular edema (DME) with center involvement in at least one eye, including those with focal or diffuse DME.
  • ETDRS letter score in the study eye of 55 letters or worse (approximate Snellen equivalent of 20/80). The non-study eye (fellow eye) should be ≥ 60 letters or better (approximate Snellen equivalent of 20/63) at Day 1 pre-dose.
  • Safe to withhold treatment of the study eye with laser photocoagulation, intravitreal steroid injection, or intravitreal vascular endothelial growth factor (VEGF) inhibitor (Part 1) for the duration of the study.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Proliferative diabetic retinopathy in the study eye, with the exception of tufts of neovascularization less than 1 disc area with no vitreous hemorrhage.
  • Any progressive disease of the retina (e.g. uveitis, rod-cone dystrophy) or optic nerve (e.g. glaucoma) other than diabetic retinopathy.
  • Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, scleritis, endophthalmitis, as well as idiopathic or autoimmune-associated uveitis in either eye.
  • Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia).
  • Cataract surgery in the study eye, Yttrium-Aluminum-Garnet (YAG) laser capsulotomy or any intraocular surgery within the past 6 months preceding Day 1.
  • Use of systemic anticoagulant therapy during the study, e.g., warfarin, heparin, etc. The use of aspirin is not an exclusion.
  • Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential, unless using highly effective methods of contraception during dosing of study treatment.
  • Other protocol-defined exclusion criteria may apply.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281292


Sponsors and Collaborators
Alcon Research
Novartis Institutes for BioMedical Research
Investigators
Study Director: Sr. Clinical Scientist, CSI, ID/Ophtha Alcon Research
  More Information

Responsible Party: Alcon Research
ClinicalTrials.gov Identifier: NCT02281292     History of Changes
Other Study ID Numbers: LKA651X-2101
First Submitted: October 30, 2014
First Posted: November 3, 2014
Last Update Posted: December 11, 2015
Last Verified: December 2015

Keywords provided by Alcon Research:
Diabetic Macular Edema
Intravitreal
Retina
Ophthalmology
Lucentis
OCT

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Pharmaceutical Solutions
Ranibizumab
Ophthalmic Solutions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents