Clinical trial NCT00536016: A Phase 1 Safety Study of Single and Repeated Doses of JSM6427 (Intravitreal Injection) to Treat AMD
Official title: A Phase 1 Open Label Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of Single and Repeated Doses of JSM6427 Following Administration by Intravitreal Injection in Patients With Neovascular AMD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Macular Degeneration
Keywords: AMD
Neovascular Age-Related Macular Degeneration
Lead sponsor: Jerini Ophthalmic
Sponsor class: INDUSTRY
First posted: 2007-09-27
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the way and rate that the study medication, JSM6427 a potent, highly specific integrin α5β1-antagonist is absorbed, broken-down and eliminated from the body when it is given as a single dosage strength by injection into the eye. Repeated dosages will also be given to determine the highest safe dose.

Detailed description: In non-clinical models, JSM6427 can lead to the inhibition and regression of choroidal neovascularization, making α5β1 an attractive target for therapeutic strategies directed at pathological angiogenesis. JSM6427 may also interfere with other key processes in the pathogenesis of AMD, namely inflammation and fibrosis. Further, non-clinical data show that JSM6427 inhibits scarring and inflammation. Thus, JSM6427 may target multiple important pathways in the pathogenesis of neovascular AMD.

Eligibility criteria: Inclusion Criteria:

* Best corrected visual acuity in the study eye between 5 and 7 letters inclusive using and ETDRS chart (Snellen equivalent of appx. 20/800 to 20/40.
* Subfoveal choroidal neovascularization (CNV) due to AMD.
* Total area of the lesion (including blood, neovascularization and scar/atrophy) must be ≤ 12 DA, of which at least 25% must be active CNV.
* For patients with occult or non classic CNV; there must be the presence of subretinal hemorrhage (but still comprising no more than 50% of the lesion) and/or documented evidence of three or more lines of vision loss (ETDRS or equivalent) during the previous 12 weeks.
* Clear ocular media and adequate pupillary dilatation to permit good stereo fundus photography for screening.
* Intraocular pressure of 21 mm Hg or less.
* Retinal thickness ≥ 250 μm by OCT.
* Normal screening ERG
* Normal ECG

Exclusion Criteria:

* PDT within 120 days prior to screening in the study eye.
* Previous therapeutic radiation to the eye.
* Any retinovascular disease or retinal degeneration other than AMD.
* Serous pigment epithelial detachment without the presence of neovascularization.
* Presence of pigment epithelial tears or rips.
* Previous posterior vitrectomy or retinal surgery.
* Any periocular infection in the past 4 weeks.
* Concomitant therapy with anti-VEGF therapies, e.g. Avastin, Lucentis or Macugen, or previous use of these agents within 60 days of screening in the study eye.
* Concomitant therapy with intravenous or intravitreous corticosteroids or use within 90 days of screening.
* Cataract surgery in the study eye within three months of screening.
* Intraocular surgery in the study eye within three months of screening.
* Presence of ocular infection in the study eye.
* Presence of severe myopia (-8 diopters or greater) in the study eye.
* Allergy to or prior significant adverse reaction to fluorescein.
* Any major surgical procedure within one month of trial entry.

Primary outcomes:
measure: Safety and Tolerability to determine the MTD
timeFrame: 2 weeks after each dose
Secondary outcomes:
measure: To evaluate the systemic pharmacokinetics of JSM6427 following single and repeat doses by intravitreal injection and to assess exploratory efficacy potential of JSM6427
timeFrame: 1 year
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Research Institute
state: Michigan
city: Oklahoma City
country: United States
facility: Dean McGee Eye Institute
state: Oklahoma
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Houston
country: United States
facility: Vitreoretinal Consultants
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
Study officials:
affiliation: Jerini Ophthalmic
name: Anthony Adamis, MD
role: STUDY_CHAIR
References: