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

August 22, 2016 updated by: Lpath, Inc.

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 Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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 Spectral Domain Optical Coherence Tomography (SD-OCT), (ii) leakage on fluorescein angiogram (FA), and (iii) an average central subfield thickness of ≥250 μm. Additionally, each subject will have previously received a minimum of 3 intravitreous (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) Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected visual acuity (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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
158

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Peoria, Arizona, United States, 85381
        • Retina Consultants of Arizona
      • Phoenix, Arizona, United States, 85020
        • Associated Retina Consultants
      • Phoenix, Arizona, United States, 85014
        • Retina Consultants of Arizona
      • Tucson, Arizona, United States, 85704
        • Retina Centers, P.C.
    • California
      • Beverly Hills, California, United States, 90211
        • Retina-Vitreous Associates Medical Group
      • Campbell, California, United States, 95008
        • Retinal Diagnostic Center
      • Glendale, California, United States, 91203
        • Specialty Eye Care Medical Center
      • Laguna Hills, California, United States, 92653
        • Retina Associates of Orange County
      • Mountain View, California, United States, 94040
        • Northern California Retina Vitreous Associates
      • New Albany, California, United States, 47150
        • Sagar Kenyon American Eye Institute
      • Sacramento, California, United States, 95819
        • Retinal Consultants Medical Group, Inc.
      • Santa Ana,, California, United States, 92705
        • Orange County Retina Medical Group
      • Ventura, California, United States, 93003
        • Miramar Eye Specialists
    • Florida
      • Boynton Beach, Florida, United States, 33426
        • Florida Eye Microsurgical Institute
      • Ft. Myers, Florida, United States, 33907
        • Retina Health Center
      • Pensacola, Florida, United States, 32503
        • Retina Specialty Institute
      • Plantation, Florida, United States, 33324
        • Fort Lauderdale Eye Institute
      • Stuart, Florida, United States, 34994
        • East Florida Eye Institute
      • Winter Haven, Florida, United States, 33880
        • Center for Retina & Macular Disease
    • Hawaii
      • Aiea, Hawaii, United States, 96701
        • Retina Consultants Of Hawaii
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Midwest Eye Institute
    • Kansas
      • Wichita, Kansas, United States, 67226
        • Central Plains Eye MDs
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Bennett & Bloom Eye Centers
    • Maryland
      • Chevy Chase, Maryland, United States, 20815
        • Retina Group of Washington
      • Towson, Maryland, United States, 21204
        • Retina Specialists
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Ophthalmic Consultants of Boston
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
      • Jackson, Michigan, United States, 49202
        • TLC Eye Care and Laser Center
      • Southfield, Michigan, United States, 48034
        • Retina Consultants of Michigan
    • New York
      • Shirley, New York, United States, 11967
        • Island Retina
    • North Carolina
      • Charlotte, North Carolina, United States, 28210
        • Charlotte Eye Ear Nose & Throat Associates
    • Oregon
      • Ashland, Oregon, United States, 97520
        • Retina & Vitreous Center SO
    • Pennsylvania
      • West Mifflin, Pennsylvania, United States, 15122
        • Associates in Ophthalmology
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Palmetto Retina Center
    • Texas
      • Abilene, Texas, United States, 79606
        • Retina Research Institute of Texas
      • Austin, Texas, United States, 78705
        • Austin Retina Associates
      • Austin, Texas, United States, 78705
        • Retina Research Center
      • Dallas, Texas, United States, 75231
        • Texas Retina Associates
      • Harlingen, Texas, United States, 78550
        • Valley Retina Institute
      • San Antonio, Texas, United States, 78240
        • Medical Center Ophthalmology Associates
      • San Antonio, Texas, United States, 78240
        • Retina Associates of South Texas
    • Utah
      • Salt Lake City, Utah, United States, 84107
        • Rocky Mountain Retina Consultants
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Retina Group of Washington
    • Washington
      • Spokane, Washington, United States, 99204
        • Spokane Eye Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 pigment epithelial detachment (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 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
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Monotherapy
4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months
Drug: 4.0 mg iSONEP
4.0 mg iSONEP given monthly intravitreously for 4 months
Other Names:
  • sonepcizumab
Drug: sham injection
administered monthly for 4 months
Other Names:
  • placebo
Experimental: 0.5 mg iSONEP & Lucentis/Avastin/Eylea
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
0.5 mg iSONEP given monthly intravitreously for 4 months
Other Names:
  • sonepcizumab
Drug: 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
Other Names:
  • aflibercept
  • bevacizumab
  • ranibizumab
Experimental: 4.0 mg iSONEP & Lucentis/Avastin/Eylea
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
4.0 mg iSONEP given monthly intravitreously for 4 months
Other Names:
  • sonepcizumab
Drug: 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
Other Names:
  • aflibercept
  • bevacizumab
  • ranibizumab
Active Comparator: Lucentis or Avastin or Eylea
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: sham injection
administered monthly for 4 months
Other Names:
  • placebo
Drug: 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
Other Names:
  • aflibercept
  • bevacizumab
  • ranibizumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)
Time Frame: Baseline to Day 120
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change in Central Subfield Retinal Thickness
Time Frame: Baseline to Day 120
Baseline to Day 120
Mean Change in CNV Lesion Area as Determined by Fluorescein Angiography (FA).
Time Frame: Baseline to Day 120
Baseline to Day 120
Proportion of Subjects Gaining Greater Than or Equal to 0, 5, 10 and 15 Letters on the ETDRS Chart.
Time Frame: Baseline to Day 120
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
Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA.
Time Frame: Baseline to Day 120
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. One line is equivalent to 5 letters, so a loss of 3 lines is a loss of 15 letters.
Baseline to Day 120
Proportion of Subjects With ETDRS BCVA of 20/40 or Better.
Time Frame: Baseline to Day 120
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. 20/40 Snellen corresponds to a range of 69-73 letters by ETDRS.
Baseline to Day 120
Proportion of Subjects With Adverse Events.
Time Frame: Baseline to Day 120
Baseline to Day 120

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lpath, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Dario A Paggiarino, MD, Lpath, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 9, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 10, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 11, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 17, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LT1009-Oph-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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