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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lpath, Inc.
ClinicalTrials.gov Identifier:
NCT01414153
First received: August 9, 2011
Last updated: August 22, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Exudative Age-related Macular Degeneration
Drug: 4.0 mg iSONEP
Drug: 0.5 mg iSONEP
Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
Drug: sham injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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 Choroidal Neovascularization (CNV) Secondary to Age-related Macular Degeneration (AMD)

Resource links provided by NLM:


Further study details as provided by Lpath, Inc.:

Primary Outcome Measures:
  • Mean Change in Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Change in Central Subfield Retinal Thickness [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: No ]
  • Mean Change in CNV Lesion Area as Determined by Fluorescein Angiography (FA). [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Proportion of Subjects Losing 3 Lines or More in ETDRS BCVA. [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: No ]
    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.

  • Proportion of Subjects With ETDRS BCVA of 20/40 or Better. [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: No ]
    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.

  • Proportion of Subjects With Adverse Events. [ Time Frame: Baseline to Day 120 ] [ Designated as safety issue: Yes ]

Enrollment: 158
Study Start Date: August 2012
Study Completion Date: June 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: sonepcizumab
Drug: sham injection
administered monthly for 4 months
Other Name: 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 Name: 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:
  • ranibizumab
  • bevacizumab
  • aflibercept
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 Name: 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:
  • ranibizumab
  • bevacizumab
  • aflibercept
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: 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:
  • ranibizumab
  • bevacizumab
  • aflibercept
Drug: sham injection
administered monthly for 4 months
Other Name: placebo

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.
  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414153

  Show 44 Study Locations
Sponsors and Collaborators
Lpath, Inc.
Investigators
Study Director: Dario A Paggiarino, MD Lpath, Inc.
  More Information

Responsible Party: Lpath, Inc.
ClinicalTrials.gov Identifier: NCT01414153     History of Changes
Other Study ID Numbers: LT1009-Oph-003 
Study First Received: August 9, 2011
Results First Received: June 27, 2016
Last Updated: August 22, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Lpath, Inc.:
choroidal neovascularization
age-related macular degeneration
iSONEP
sonepcizumab
Lucentis
ranibizumab
Avastin
bevacizumab
Eylea
aflibercept

Additional relevant MeSH terms:
Macular Degeneration
Choroidal Neovascularization
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Choroid Diseases
Uveal Diseases
Neovascularization, Pathologic
Metaplasia
Pathologic Processes
Bevacizumab
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on December 09, 2016