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

NCT02281292 | Withdrawn Phase 1 DMC

• 1 other identifier: LKA651X-2101
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diabetic Macular Edema

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of subjects with a serious adverse event (SAE) that, in the opinion of the investigator, is related to the study drug

  Up to Day 85

• Number of subjects experiencing a non-serious adverse event

  Up to Day 85

Secondary Outcomes (7)

• 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))

  Up to Day 85

• 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))

  Up to Day 85

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

  Up to Day 85

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

  Up to Day 85

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

  Up to Day 85

Study Arms (4)

LKA651 (Part 1)

EXPERIMENTAL

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

Biological: LKA651 ophthalmic solution

Sham injection (Part 1)

PLACEBO COMPARATOR

Sham injection in the study eye

Biological: Sham injection

LKA651 and Lucentis (Part 2)

EXPERIMENTAL

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

Sham injection and Lucentis (Part 2)

PLACEBO COMPARATOR

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; Biological: Sham injection

Interventions

LKA651 ophthalmic solution BIOLOGICAL

LKA651 (Part 1); LKA651 and Lucentis (Part 2)

Ranibizumab ophthalmic solution BIOLOGICAL

Also known as: Lucentis®

LKA651 and Lucentis (Part 2); Sham injection and Lucentis (Part 2)

Sham injection BIOLOGICAL

Mock injection administered as an empty hub without needle

Sham injection (Part 1); Sham injection and Lucentis (Part 2)

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.
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Alcon Research: lead
• Novartis Institutes for BioMedical Research: collaborator

MeSH Terms

Interventions

Ranibizumab; salicylhydroxamic acid

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sr. Clinical Scientist, CSI, ID/Ophtha

  Alcon Research

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 3, 2014
• Study Start: December 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: December 11, 2015

Record last verified: 2015-12