A Phase 1 Safety Study of Single and Repeated Doses of JSM6427 (Intravitreal Injection) to Treat AMD

Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536016
• Other study ID #: JO642701
• Status: Completed
• Phase: Phase 1
• First received: September 25, 2007
• Last updated: September 20, 2010
• Start date: September 2007
• Est. completion date: December 2009

Study information

• Verified date: September 2010
• Source: Jerini Ophthalmic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Macular Degeneration

Intervention

Drug:
• JSM6427
Weekly intravitreal injections for up to 4 weeks, first dose strength is one dose below the MTD. Dose strength concentrations: 1.5 mg/ml, 3 mg/ml, 7.5 mg/ml 04 15 mg/ml.

Locations

Country	Name	City	State
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Retina Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Vitreoretinal Consultants	Houston	Texas
United States	Valley Retina Institute	McAllen	Texas
United States	Dean McGee Eye Institute	Oklahoma City	Oklahoma
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	William Beaumont Research Institute	Royal Oak	Michigan
United States	Palmetto Retina Center	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Jerini Ophthalmic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability to determine the MTD		2 weeks after each dose	Yes
Secondary	To evaluate the systemic pharmacokinetics of JSM6427 following single and repeat doses by intravitreal injection and to assess exploratory efficacy potential of JSM6427		1 year	Yes