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

NCT01414153 | Completed Phase 2 Results DMC

• 1 other identifier: LT1009-Oph-003
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 44

Brief 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.

Conditions

Exudative Age-related Macular Degeneration

Keywords

choroidal neovascularization; age-related macular degeneration; iSONEP; sonepcizumab; Lucentis; ranibizumab; Avastin; bevacizumab; Eylea; aflibercept

Outcome Measures

Primary Outcomes (1)

• Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)

  Visual function was assessed using the ETDRS protocol, for which numerical scores range from 0 to 100 (roughly equivalent to 20/10 vision as measured by Snellen). A higher score represents better functioning. A positive number represents an increase in number of letters read correctly.

  Baseline to Day 120

Secondary Outcomes (6)

• Mean Change in Central Subfield Retinal Thickness

  Baseline to Day 120

• Mean Change in CNV Lesion Area as Determined by Fluorescein Angiography (FA).

  Baseline to Day 120

• Proportion of Subjects Gaining Greater Than or Equal to 0, 5, 10 and 15 Letters on the ETDRS Chart.

  Baseline to Day 120

• Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA.

  Baseline to Day 120

• Proportion of Subjects With ETDRS BCVA of 20/40 or Better.

  Baseline to Day 120

Study Arms (4)

Monotherapy

EXPERIMENTAL

4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months

Drug: 4.0 mg iSONEP; Drug: sham injection

0.5 mg iSONEP & Lucentis/Avastin/Eylea

EXPERIMENTAL

0.5 mg iSONEP and 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months

Drug: 0.5 mg iSONEP; Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea

4.0 mg iSONEP & Lucentis/Avastin/Eylea

EXPERIMENTAL

4.0 mg iSONEP followed by 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; given monthly intravitreously for 4 months

Drug: 4.0 mg iSONEP; Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea

Lucentis or Avastin or Eylea

ACTIVE COMPARATOR

0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea followed by a sham injection; given monthly intravitreously for 4 months

Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea; Drug: sham injection

Interventions

4.0 mg iSONEP DRUG

4.0 mg iSONEP given monthly intravitreously for 4 months

Also known as: sonepcizumab

4.0 mg iSONEP & Lucentis/Avastin/Eylea; Monotherapy

0.5 mg iSONEP DRUG

0.5 mg iSONEP given monthly intravitreously for 4 months

Also known as: sonepcizumab

0.5 mg iSONEP & Lucentis/Avastin/Eylea

0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea DRUG

0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea given monthly intravitreously for 4 months

Also known as: ranibizumab, bevacizumab, aflibercept

0.5 mg iSONEP & Lucentis/Avastin/Eylea; 4.0 mg iSONEP & Lucentis/Avastin/Eylea; Lucentis or Avastin or Eylea

sham injection DRUG

administered monthly for 4 months

Also known as: placebo

Lucentis or Avastin or Eylea; Monotherapy

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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 pigment epithelial detachment (PED) (any part of which may be subfoveal) with intraretinal and/or subretinal fluid may be included

You may not qualify if:

• 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 photodynamic therapy (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 retinal angiomatous proliferation (RAP) lesions
• Presence of polypoidal choroidal vasculopathy (PCV) (if suspected, Indocyanine Green Angiography (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

Sponsors & Collaborators

• Lpath, Inc.: lead

Study Sites (44)

Retina Consultants of Arizona

Peoria, Arizona, 85381, United States

Location

Retina Consultants of Arizona

Phoenix, Arizona, 85014, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

Retina Centers, P.C.

Tucson, Arizona, 85704, United States

Location

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Retinal Diagnostic Center

Campbell, California, 95008, United States

Location

Specialty Eye Care Medical Center

Glendale, California, 91203, United States

Location

Retina Associates of Orange County

Laguna Hills, California, 92653, United States

Location

Northern California Retina Vitreous Associates

Mountain View, California, 94040, United States

Location

Sagar Kenyon American Eye Institute

New Albany, California, 47150, United States

Location

Retinal Consultants Medical Group, Inc.

Sacramento, California, 95819, United States

Location

Orange County Retina Medical Group

Santa Ana, California, 92705, United States

Location

Miramar Eye Specialists

Ventura, California, 93003, United States

Location

Florida Eye Microsurgical Institute

Boynton Beach, Florida, 33426, United States

Location

Retina Health Center

Fort Myers, Florida, 33907, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

East Florida Eye Institute

Stuart, Florida, 34994, United States

Location

Center for Retina & Macular Disease

Winter Haven, Florida, 33880, United States

Location

Retina Consultants of Hawaii

‘Aiea, Hawaii, 96701, United States

Location

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Central Plains Eye MDs

Wichita, Kansas, 67226, United States

Location

Bennett & Bloom Eye Centers

Louisville, Kentucky, 40207, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Retina Specialists

Towson, Maryland, 21204, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

TLC Eye Care and Laser Center

Jackson, Michigan, 49202, United States

Location

Retina Consultants of Michigan

Southfield, Michigan, 48034, United States

Location

Island Retina

Shirley, New York, 11967, United States

Location

Charlotte Eye Ear Nose & Throat Associates

Charlotte, North Carolina, 28210, United States

Location

Retina & Vitreous Center SO

Ashland, Oregon, 97520, United States

Location

Associates in Ophthalmology

West Mifflin, Pennsylvania, 15122, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Valley Retina Institute

Harlingen, Texas, 78550, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retina Associates of South Texas

San Antonio, Texas, 78240, United States

Location

Rocky Mountain Retina Consultants

Salt Lake City, Utah, 84107, United States

Location

Retina Group of Washington

Fairfax, Virginia, 22031, United States

Location

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

Location

MeSH Terms

Conditions

Choroidal Neovascularization; Macular Degeneration

Interventions

sonepcizumab; Ranibizumab; Bevacizumab; aflibercept; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Choroid Diseases; Uveal Diseases; Eye Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Retinal Degeneration; Retinal 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: Susan E. Hazel
• Organization: Lpath, Inc.

shazel@lpath.com

858-926-3205

Study Officials

• Dario A Paggiarino, MD

  Lpath, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 9, 2011
• First Posted: August 11, 2011
• Study Start: August 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: October 17, 2016
• Results First Posted: October 17, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (44)