Safety Study of iSONEP (Sonepcizumab/LT1009) to Treat Neovascular Age-related Macular Degeneration
Primary Purpose
Neovascular Age Related Macular Degeneration
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
iSONEP
Sponsored by
About this trial
This is an interventional treatment trial for Neovascular Age Related Macular Degeneration focused on measuring wet, AMD
Eligibility 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
Sites / Locations
- Retinal Consultants of Arizona, LTD
- Center for Retina and Macular Disease
- Midwest Eye Institute
- Vitreo-Retinal Consultants
- Wills Eye Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
iSONEP
Outcomes
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00767949
Brief Title
Safety Study of iSONEP (Sonepcizumab/LT1009) to Treat Neovascular Age-related Macular Degeneration
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Unknown status
Study Start Date
October 2008 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
August 2012 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lpath, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age Related Macular Degeneration
Keywords
wet, AMD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
iSONEP
Intervention Type
Biological
Intervention Name(s)
iSONEP
Other Intervention Name(s)
Sonepcizumab; LT1009
Intervention Description
single intravitreal injection of 0.2, 0.6, 1.0, 1.4 or 1.8 mg/eye
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Glenn Stoller, MD
Organizational Affiliation
Lpath, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Retinal Consultants of Arizona, LTD
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85014
Country
United States
Facility Name
Center for Retina and Macular Disease
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Midwest Eye Institute
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46280
Country
United States
Facility Name
Vitreo-Retinal Consultants
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
Facility Name
Wills Eye Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16530706
Citation
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.
Results Reference
background
PubMed Identifier
18723015
Citation
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.
Results Reference
background
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Safety Study of iSONEP (Sonepcizumab/LT1009) to Treat Neovascular Age-related Macular Degeneration
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