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

Sponsor:	Lpath, Inc.
Information provided by:	Lpath, Inc.
ClinicalTrials.gov Identifier:	NCT00767949

Purpose

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).

Condition	Intervention	Phase
Neovascular Age Related Macular Degeneration	Biological: iSONEP	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: age-related macular degeneration X-linked juvenile retinoschisis

MedlinePlus related topics: Macular Degeneration

U.S. FDA Resources

Further study details as provided by Lpath, Inc.:

Primary Outcome Measures:

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 [ Time Frame: Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: Active phase: 30 days post-injection; Follow-up phase: 12 months post-injection ] [ Designated as safety issue: No ]

Enrollment:	15
Study Start Date:	October 2008
Estimated Study Completion Date:	July 2010
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 iSONEP	Biological: iSONEP single intravitreal injection of 0.2, 0.6, 1.0, 1.4 or 1.8 mg/eye Other Name: Sonepcizumab; LT1009

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.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00767949

Locations

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

Sponsors and Collaborators

Lpath, Inc.

Investigators

Study Director:

Glenn Stoller, MD

Lpath, Inc.

More Information

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.

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. 2008 Aug 6; [Epub ahead of print]

Responsible Party:	Glenn Stoller, MD Head of Ocular, Lpath, Inc.
ClinicalTrials.gov Identifier:	NCT00767949 History of Changes
Other Study ID Numbers:	LT1009-Oph-001
Study First Received:	October 2, 2008
Last Updated:	August 17, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Lpath, Inc.:

wet
AMD

Additional relevant MeSH terms:

Macular Degeneration
Wet Macular Degeneration
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases

Choroid Diseases
Uveal Diseases
Neovascularization, Pathologic
Metaplasia
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012