Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD

Exudative Age-related Macular Degeneration Clinical Trial

— Nexus  

Official title:

Phase 2a, Multicenter, Masked, Randomized, Comparator Controlled Study Evaluating iSONEP™ as Monotherapy or Adjunctive Therapy to Lucentis/Avastin/Eylea Versus Lucentis/Avastin/Eylea Alone for Treatment of Subjects With CNV Secondary to AMD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01414153
• Other study ID #: LT1009-Oph-003
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2011
• Last updated: September 15, 2015
• Start date: August 2012
• Est. completion date: June 2015

Study information

• Verified date: September 2015
• Source: Lpath, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the safety and efficacy of 4 monthly injections of iSONEP given alone or in combination with Lucentis, Avastin or Eylea in subjects with wet Age-related Macular Degeneration (AMD). iSONEP not only has an anti-permeability effect, but also has anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. The drug may therefore have the ability to achieve better visual outcomes than Lucentis, Avastin or Eylea, particularly in those subjects who do not demonstrate a robust response to Lucentis, Avastin or Eylea after several monthly injections. Further, the combination of Lucentis, Avastin or Eylea and iSONEP may be additive or synergistic. By inhibiting the multiple mechanisms that contribute to exudative-AMD-related vision loss, better visual outcomes may be possible than with Lucentis, Avastin or Eylea alone.

Description:

The study will be conducted in subjects who qualify as "sub-responders" to Lucentis, Avastin or Eylea meaning that each subject has (i) residual subretinal or intra-retinal fluid observed on Cirrus or Spectralis SDOCT, (ii) leakage on FA, and (iii) an average central subfield thickness of ≥250 μm. Additionally, each subject will have previously received a minimum of 3 IVT injections of Lucentis, Avastin or Eylea within the 12-month period prior to screening. Screening must occur between 28 and 65 days from the subject's last Lucentis or Avastin treatment or between 42 and 79 days from the subject's last Eylea treatment. Subjects must be dosed within 14 days of screening, and as of the day of initial study treatment (Day 0), meet the following criteria: (i) ETDRS BCVA of ≥25 and ≤73 letters (approximately 20/320 and 20/40 on the Snellen scale), (ii) residual subretinal or intra-retinal fluid observed on Cirrus or Spectralis SDOCT, and (iii) leakage on FA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: June 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• =50 years of age with a diagnosis of wet AMD

• Subjects who have received 3 injections of Lucentis or Avastin or Eylea within 12 months prior to screening

• Active subfoveal CNV secondary to AMD (leakage on FA)

• Presence of residual subretinal or intraretinal fluid on Cirrus or Spectralis SDOCT

• SDOCT in the 1 mm central macular subfield on the retinal map analysis of =250 µm at screening

• ETDRS BCVA of =25 and =73 letters (approximately 20/320 and 20/40 on the Snellen scale) at screening and on Day 0

• In the fellow eye, ETDRS BCVA of 20/400 or better

• Subject with serous PED (any part of which may be subfoveal) with intraretinal and/or subretinal fluid may be included

Exclusion Criteria:

• Most recent IVT injection of Lucentis or Avastin fewer than 28 days and more than 65 days prior to screening

• Most recent IVT injection of Eylea fewer than 42 days and more than 79 days prior to screening

• Previous PDT or Macugen® at any time point

• Focal thermal laser or grid laser within 3 months prior to Day 0

• Use of IVT, subtenon or subconjunctival steroids within 3 months prior to Day 0

• Use of topical ophthalmic corticosteroids 2 weeks prior to Day 0

• Intraocular surgery, including cataract surgery, and / or laser of any type within 3 months prior to Day 0 or anticipated need for ocular surgery or ophthalmic laser treatment during the study period

• Subjects previously treated with, or are currently receiving treatment with another investigational agent or device for neovascular AMD in the study eye

• Retinal total lesion size >12 disc areas (30.5 mm2), including blood, scars and neovascularization as assessed by FA in the study eye

• Presence of a fibrovascular PED extending underneath the center of the fovea

• Presence of RAP (retinal angiomatous proliferation) lesions

• Presence of PCV (if suspected, ICG should be performed at the discretion of the Investigator)

• Subretinal hemorrhage in the study eye if any of the following is true: (i) the subretinal hemorrhage represents 50% or more of the total lesion area; (ii) subfoveal blood is 1 or more disc areas in size (iii) subfoveal blood where the fovea is surrounded by less than 270 degrees of visible CNV on FA

• Scar or fibrosis making up >50% of total lesion area in the study eye

• Anatomic damage to the center of the fovea including fibrosis, scarring or atrophy

• History of a retinal pigment epithelial tear

• History of vitreous hemorrhage within 4 weeks prior to screening in the study eye

• Clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye

• Uncontrolled glaucoma defined as: (i) as intraocular pressure =25 mmHg despite treatment with anti glaucoma medication in the study eye or (ii) by the Investigator

• Prior trabeculectomy or other filtration surgery in the study eye (prior laser trabeculoplasty is allowed)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Exudative Age-related Macular Degeneration
• Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• 4.0 mg iSONEP
4.0 mg iSONEP given monthly intravitreously for 4 months
• 0.5 mg iSONEP
0.5 mg iSONEP given monthly intravitreously for 4 months
• 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea given monthly intravitreously for 4 months
• sham injection
administered monthly for 4 months

Locations

Country	Name	City	State
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Retina Consultants of Hawaii	Aiea	Hawaii
United States	Retina & Vitreous Center SO	Ashland	Oregon
United States	Austin Retina Associates	Austin	Texas
United States	Retina Research Center	Austin	Texas
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Florida Eye Microsurgical Institute	Boynton Beach	Florida
United States	Retinal Diagnostic Center	Campbell	California
United States	Charlotte Eye Ear Nose & Throat Associates	Charlotte	North Carolina
United States	Retina Group of Washington	Chevy Chase	Maryland
United States	Texas Retina Associates	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Retina Group of Washington	Fairfax	Virginia
United States	Retina Health Center	Ft. Myers	Florida
United States	Specialty Eye Care Medical Center	Glendale	California
United States	Valley Retina Institute	Harlingen	Texas
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	TLC Eye Care and Laser Center	Jackson	Michigan
United States	Retina Associates of Orange County	Laguna Hills	California
United States	Bennett & Bloom Eye Centers	Louisville	Kentucky
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Sagar Kenyon American Eye Institute	New Albany	California
United States	Retina Specialty Institute	Pensacola	Florida
United States	Retina Consultants of Arizona	Peoria	Arizona
United States	Associated Retina Consultants	Phoenix	Arizona
United States	Retina Consultants of Arizona	Phoenix	Arizona
United States	Fort Lauderdale Eye Institute	Plantation	Florida
United States	Retinal Consultants Medical Group, Inc.	Sacramento	California
United States	Rocky Mountain Retina Consultants	Salt Lake City	Utah
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retina Associates of South Texas	San Antonio	Texas
United States	Orange County Retina Medical Group	Santa Ana,	California
United States	Island Retina	Shirley	New York
United States	Retina Consultants of Michigan	Southfield	Michigan
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	East Florida Eye Institute	Stuart	Florida
United States	Retina Specialists	Towson	Maryland
United States	Retina Centers, P.C.	Tucson	Arizona
United States	Miramar Eye Specialists	Ventura	California
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Associates in Ophthalmology	West Mifflin	Pennsylvania
United States	Central Plains Eye MDs	Wichita	Kansas
United States	Center for Retina & Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Lpath, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in Best Corrected Visual Acuity (BCVA) by ETDRS		120 days	No
Secondary	Mean change in central subfield retinal thickness		120 days	No
Secondary	Mean change in CNV lesion area as determined by FA.		120 days	No
Secondary	Proportion of subjects gaining greater than or equal to 0, 5, 10 and 15 letters on the ETDRS chart.		120 days	No
Secondary	Proportion of subjects losing 3 lines or more in ETDRS BCVA.		120 days	No
Secondary	Proportion of subjects with ETDRS BCVA of 20/50 or better.		120 days	No
Secondary	Proportion of subjects with adverse events.		120 days	Yes