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

This study is currently recruiting participants.
Verified March 2014 by Lpath, Inc.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Lpath, Inc.
ClinicalTrials.gov Identifier:
NCT01414153
First received: August 9, 2011
Last updated: March 18, 2014
Last verified: March 2014

August 9, 2011
March 18, 2014
August 2012
November 2014   (final data collection date for primary outcome measure)
Mean change in Best Corrected Visual Acuity (BCVA) by ETDRS from Day 0 to Day 120. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01414153 on ClinicalTrials.gov Archive Site
  • Mean change in central subfield retinal thickness from Day 0 to Day 120. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Mean change in CNV lesion area from Day 0 to Day 120 as determined by FA. [ Time Frame: 120 days ] [ 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: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects losing 3 lines or more in ETDRS BCVA. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects with ETDRS BCVA of 20/50 or better. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects with adverse events. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
  • Single and multiple-dose pharmacokinetics [ Time Frame: Pre-dose on dosing days (Days 0, 30, 60 and 90) and during non-dosing study visits on Days 7, 14, 67, 74, 120 and Month 5 ] [ Designated as safety issue: Yes ]
  • Changes in anti-drug antibodies (ADA) during study and follow-up period [ Time Frame: Pre-dose on dosing days (Days 0, 30, 60 and 90) and during non-dosing study visits on Days 67, 74, 120, Months 5 and 9 ] [ Designated as safety issue: Yes ]
  • Mean change in central subfield retinal thickness from Day 0 to Day 120. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Mean change in CNV lesion area from Day 0 to Day 120 as determined by FA. [ Time Frame: 120 days ] [ 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: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects losing 3 lines or more in ETDRS BCVA. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects with ETDRS BCVA of 20/50 or better. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
  • Proportion of subjects with adverse events. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy and Safety Study of iSONEP With & Without Lucentis/Avastin/Eylea to Treat Wet AMD
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Exudative Age-related Macular Degeneration
  • Drug: 4.0 mg iSONEP
    4.0 mg iSONEP given monthly intravitreously for 4 months
    Other Name: sonepcizumab
  • 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
  • Drug: sham injection
    administered monthly for 4 months
    Other Name: placebo
  • Experimental: Monotherapy
    4.0 mg iSONEP followed by sham injection; given monthly intravitreously for 4 months
    Interventions:
    • Drug: 4.0 mg iSONEP
    • Drug: sham injection
  • 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
    Interventions:
    • Drug: 0.5 mg iSONEP
    • Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
  • 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
    Interventions:
    • Drug: 4.0 mg iSONEP
    • Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
  • 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
    Interventions:
    • Drug: 0.5 mg Lucentis or 1.25 mg Avastin or 2 mg Eylea
    • Drug: sham injection
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
April 2015
November 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • ≥50 years of age with a diagnosis of wet AMD
  • Subjects who have received 3 injections of Lucentis or Avastin 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)
Both
50 Years and older
No
Not Provided
United States
 
NCT01414153
LT1009-Oph-003
Yes
Lpath, Inc.
Lpath, Inc.
Pfizer
Study Director: Susan Hazel Lpath, Inc.
Lpath, Inc.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP