Safety Study of iSONEP (Sonepcizumab/LT1009) to Treat Neovascular Age-related Macular Degeneration

A Phase 1, Dose-Escalating, Multi-Center, Study of iSONEP (Sonepcizumab [LT1009]) Administered as an Intravitreal Injection to Subjects With Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a disease that, in time, destroys the macula, which is the central part of the retina that gives sharp central vision. The primary purpose of this study is to assess the safety of iSONEP which is a humanized monoclonal antibody against a bioactive lipid, sphingosine 1-phosphate (S1P).

Study Overview

• Status: Unknown
• Conditions: Neovascular Age Related Macular Degeneration
• Intervention / Treatment: Biological: iSONEP

Detailed Description

S1P modulates the AMD-associated processes of angiogenesis, inflammation and fibrosis. A potential strategy for treating choroidal neovascularization associated with AMD is to reduce the biologically available extracellular levels of S1P. iSONEP is highly selective for S1P and binds with picomolar affinity. Lpath proposes that iSONEP would deprive many cell types (fibroblasts, pericytes, vascular endothelial cells and inflammatory) of important growth and survival factors thus targeting the multiple maladaptive processes of exudative AMD that ultimately result in the loss of photoreceptors, their supporting cells, and visual acuity. Targeting simultaneously multiple components of the choroidal neovascular response is a novel approach and has the potential to be more potent than "single-targeted" therapeutics such as anti-VEGF therapies.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Consultants of Arizona, LTD
  • Florida
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Midwest Eye Institute
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Vitreo-Retinal Consultants
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Institute

Participation Criteria

Eligibility Criteria

• 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 and older
• BCVA ETDRS letter score in study eye between 20-57 letters using ETDRS refraction (Snellen of 20/70-20/400)
• Any CNV secondary to AMD in study eye, classic, minimally classic or occult with leakage on fluorescein angiography and intraretinal or subretinal fluid on OCT
• Visual acuity in fellow eye must be 20/800 or better at 4 meters
• Able to read, understand and sign the consent form before entering into study

Exclusion Criteria:

• Ocular disease other than CNV that could compromise vision in study eye
• Systemic immunosuppressive medication/therapy (e.g., chemotherapy, steroids)
• Uncontrolled hypertension and/or arrhythmias
• QT/QTc interval measurement >450 msec
• Cancer within the last 2 years except superficial basal or squamous cell skin cancer or cervical carcinoma in situ
• Have angioid streaks, presumed ocular histoplasmosis syndrome, myopia (>8 diopters) or CNV secondary to other causes than AMD
• Any additional ocular diseases which have irreversibly compromised visual acuity of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema and severe non-proliferative diabetic retinopathy
• Any intraocular or general surgery, including cataract surgery, within 2 months of Day 1
• History of uveitis in either eye
• Any ocular or periocular infection within 4 weeks prior to Day 1
• Active ocular inflammation grade trace and above
• Cup to disc ratio >0.8, IOP >21 mmHg in glaucoma subjects treated with more than 2 ocular hypotensive agents
• Previous pars plana vitrectomy or trabeculectomy in study eye
• History of anterior vitrectomy
• Inability to obtain photographs, FA or OCT to document CNV, e.g. due to media opacity, allergy to fluorescein dye or lack of venous access
• Aphakia
• Previous intravitreal Macugen, Avastin or Lucentis (injection or drug device implantation) in study eye within 6 weeks or triamcinolone within 6 months
• Receiving or requiring chronic concomitant therapy with systemic anti-angiogenic treatments p.o., parenteral (excluding inhaled steroids) (>5 mg) or topical corticosteroids in the study eye
• PDT within 12 weeks prior to Day 1
• Subjects taking systemic anticoagulants such as warfarin
• Investigational agents or devices within 6 weeks prior to Day 1
• Females who are pregnant or nursing and women of child bearing potential who are not using adequate contraceptive precautions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; iSONEP	Biological: iSONEP; single intravitreal injection of 0.2, 0.6, 1.0, 1.4 or 1.8 mg/eye; Other Names: Sonepcizumab; LT1009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine safety, tolerability, maximum tolerated dose and dose-limiting toxicity of iSONEP following a single intravitreal injection to subjects with choroidal neovascularization secondary to AMD	Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection

Secondary Outcome Measures

Outcome Measure	Time Frame
To characterize systemic pharmacokinetics, evaluate the immunogenicity, and investigate preliminary efficacy on retinal lesion thickness determined by OCT; size and extent of CNV and lesion area; and visual acuity	Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection

Collaborators and Investigators

• Sponsor: Lpath, Inc.
• Investigators: Study Director: Glenn Stoller, MD, Lpath, Inc.

Publications and helpful links

General Publications

• Visentin B, Vekich JA, Sibbald BJ, Cavalli AL, Moreno KM, Matteo RG, Garland WA, Lu Y, Yu S, Hall HS, Kundra V, Mills GB, Sabbadini RA. Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages. Cancer Cell. 2006 Mar;9(3):225-38. doi: 10.1016/j.ccr.2006.02.023.
• Caballero S, Swaney J, Moreno K, Afzal A, Kielczewski J, Stoller G, Cavalli A, Garland W, Hansen G, Sabbadini R, Grant MB. Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub-retinal fibrosis in a murine model of laser-induced choroidal neovascularization. Exp Eye Res. 2009 Mar;88(3):367-77. doi: 10.1016/j.exer.2008.07.012. Epub 2008 Aug 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: October 2, 2008
• First Submitted That Met QC Criteria: October 6, 2008
• First Posted (Estimate): October 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 16, 2012
• Last Update Submitted That Met QC Criteria: April 13, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: AMD; wet
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: LT1009-Oph-001