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

Primary Purpose

Diabetic Macular Edema

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

LKA651 ophthalmic solution

Ranibizumab ophthalmic solution

Sham injection

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring Diabetic Macular Edema, Intravitreal, Retina, Ophthalmology, Lucentis, OCT

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

LKA651 (Part 1)

Sham injection (Part 1)

LKA651 and Lucentis (Part 2)

Sham injection and Lucentis (Part 2)

Arm Description

LKA651 ophthalmic solution in 1 of 5 concentrations, administered as a single IVT injection in the study eye

Sham injection in the study eye

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

Sham injection in the study eye, followed by ranibizumab ophthalmic solution, 0.5 mg injection in the same eye 30 minutes later

Outcomes

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

Number of subjects experiencing a non-serious adverse event

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))

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))

Contingent upon observed serum concentration levels

The observed maximum serum concentration following drug administration [mass / volume] (Cmax)

Contingent upon observed serum concentration levels

The time to reach the maximum serum concentration after drug administration [time] (Tmax)

Contingent upon observed serum concentration levels

The dose normalized observed maximum serum concentration following drug administration [mass*dose / volume] (Cmax/D)

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)

Central subfield thickness

Contingent upon observed serum concentration levels

Full Information

NCT ID

NCT02281292

First Posted

October 30, 2014

Last Updated

December 9, 2015

Sponsor

Alcon Research

Collaborators

Novartis Institutes for BioMedical Research

1. Study Identification

Unique Protocol Identification Number

NCT02281292

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Management Decision

Study Start Date

December 2015 (undefined)

Primary Completion Date

June 2017 (Anticipated)

Study Completion Date

June 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alcon Research

Collaborators

Novartis Institutes for BioMedical Research

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Macular Edema

Keywords

Diabetic Macular Edema, Intravitreal, Retina, Ophthalmology, Lucentis, OCT

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LKA651 (Part 1)

Arm Type

Experimental

Arm Description

LKA651 ophthalmic solution in 1 of 5 concentrations, administered as a single IVT injection in the study eye

Arm Title

Sham injection (Part 1)

Arm Type

Placebo Comparator

Arm Description

Sham injection in the study eye

Arm Title

LKA651 and Lucentis (Part 2)

Arm Type

Experimental

Arm Description

Arm Title

Sham injection and Lucentis (Part 2)

Arm Type

Placebo Comparator

Arm Description

Sham injection in the study eye, followed by ranibizumab ophthalmic solution, 0.5 mg injection in the same eye 30 minutes later

Intervention Type

Biological

Intervention Name(s)

LKA651 ophthalmic solution

Intervention Type

Biological

Intervention Name(s)

Ranibizumab ophthalmic solution

Other Intervention Name(s)

Lucentis®

Intervention Type

Biological

Intervention Name(s)

Sham injection

Intervention Description

Mock injection administered as an empty hub without needle

Primary Outcome Measure Information:

Title

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

Title

Number of subjects experiencing a non-serious adverse event

Time Frame

Up to Day 85

Secondary Outcome Measure Information:

Title

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))

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

Title

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))

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

Title

The observed maximum serum concentration following drug administration [mass / volume] (Cmax)

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

Title

The time to reach the maximum serum concentration after drug administration [time] (Tmax)

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

Title

The dose normalized observed maximum serum concentration following drug administration [mass*dose / volume] (Cmax/D)

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

Title

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

Title

Central subfield thickness

Description

Contingent upon observed serum concentration levels

Time Frame

Up to Day 85

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sr. Clinical Scientist, CSI, ID/Ophtha

Organizational Affiliation

Alcon Research

Official's Role

Study Director

12. IPD Sharing Statement

Learn more about this trial

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

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