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Efficacy and Safety Study of iSONEP With and Without Lucentis/Avastin to Treat Age-related Macular Degeneration (AMD) (Nexus)

This study is currently recruiting participants.
Verified August 2012 by Lpath, Inc.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Lpath, Inc.
ClinicalTrials.gov Identifier:
NCT01414153
First received: August 9, 2011
Last updated: April 17, 2013
Last verified: August 2012
History of Changes
  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 or Avastin 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 (or Avastin), particularly in those subjects who do not demonstrate a robust response to Lucentis (or Avastin) after several monthly injections. Further, the combination of Lucentis (or Avastin) 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 or Avastin alone.


Condition Intervention Phase
Exudative Age-related Macular Degeneration
 Drug: iSONEP
Drug: 0.5 mg iSONEP with ranibizumab or bevacizumab
Drug: 4.0 mg iSONEP with ranibizumab or bevacizumab
Drug: ranibizumab or bevacizumab
 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: A Phase 2a, Multi-center, Masked, Randomized, Comparator Controlled Study Evaluating iSONEP™ as Monotherapy or Adjunctive Therapy to Lucentis®/Avastin® Versus Lucentis/Avastin Alone for the Treatment of Subjects With CNV Secondary to AMD

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Lpath, Inc.:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 160
Study Start Date: August 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: September 2013 (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: iSONEP
4.0 mg iSONEP followed by a sham injection; given monthly intravitreously for 4 months
Other Name: sonepcizumab
Experimental: 0.5 mg iSONEP with ranibizumab or bevacizumab
0.5 mg iSONEP followed by 0.5 mg ranibizumab or 1.25 mg bevacizumab; given monthly intravitreously for 4 months
 Drug: 0.5 mg iSONEP with ranibizumab or bevacizumab
0.5 mg iSONEP with 0.5 mg ranibizumab or 1.25 mg bevacizumab; given monthly intravitreously for 4 months
Other Names:
  • Lucentis
  • Avastin
  • sonepcizumab
Experimental: 4.0 mg iSONEP with ranibizumab or bevacizumab
4.0 mg iSONEP followed by 0.5 mg ranibizumab or 1.25 mg bevacizumab; given monthly intravitreously for 4 months
 Drug: 4.0 mg iSONEP with ranibizumab or bevacizumab
4.0 mg iSONEP followed by 0.5 mg ranibizumab or 1.25 mg bevacizumab; given monthly intravitreously for 4 months
Other Names:
  • Lucentis
  • Avastin
  • sonepcizumab
Active Comparator: ranibizumab or bevacizumab
0.5 mg ranibizumab or 1.25 mg bevacizumab followed by a sham injection; given monthly intravitreously for 4 months
 Drug: ranibizumab or bevacizumab
0.5 mg ranibizumab or 1.25 mg bevacizumab followed by a sham injection; given monthly intravitreously for 4 months
Other Names:
  • Lucentis
  • Avastin

Detailed Description:

The study will be conducted in subjects who qualify as "sub-responders" to Lucentis or Avastin 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 total of 3-10 IVT injections of Lucentis or Avastin within a 12-month period prior to screening. Screening must occur between 28 and 65 days from the subject's last Lucentis or Avastin 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.

  Eligibility

Ages Eligible for Study:   50 Years and older
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 3-10 IVT 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
  • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01414153

  Show 46 Study Locations
Sponsors and Collaborators
Lpath, Inc.
Pfizer
Investigators
Study Chair: Glenn Stoller, MD Lpath, Inc.
  More Information

No publications provided

Responsible Party: Lpath, Inc.
ClinicalTrials.gov Identifier: NCT01414153     History of Changes
Other Study ID Numbers: LT1009-Oph-003
Study First Received: August 9, 2011
Last Updated: April 17, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Bevacizumab
Angiogenesis Inhibitors
 Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013