Safety and Preliminary Efficacy Study of WST11 (Stakel®)-Mediated VTP Therapy in Subjects With CNV Associated With AMD

A Phase IIa, Safety and Preliminary Effects Study of WST11 (Stakel®) Mediated Vascular-Targeted Photodynamic (VTP) Therapy in Subjects With Choroidal Neovascularization (CNV) Associated With Age-Related Macular Degeneration (AMD)

The objectives of this study are to evaluate the safety(first objective) and efficacy(second objective)of an experimental drug product,Stakel®, in the treatment of neovascular Age related Macular Degeneration (AMD). The drug product is activated in patients by exposure to light at a specific wavelength ("Vascular Targeted Photodynamic therapy", "VTP"). The exploratory objective is to assess whether it is possible to delay or reduce the requirement for anti Vascular Endothelium Growth Factor (anti VEGF) intravitreal therapy in the first 12 weeks after VTP.

All subjects will have a 52 weeks safety follow up telephone call (Not for Adverse Events (AEs) collection).

Study Overview

• Status: Terminated
• Conditions: Macular Degeneration; Choroidal Neovascularization
• Intervention / Treatment: Drug: STAKEL

Detailed Description

The primary objective of this Phase IIa clinical study is to evaluate the safety of treatment with Stakel®-mediated VTP in subjects with neovascular AMD. The secondary objective of this Phase IIa clinical study is to explore the effect of treatment with Stakel®-mediated VTP in subjects with neovascular AMD. The exploratory objective is to assess whether it is possible to delay or reduce the requirement for anti Vascular Endothelium Growth Factor (anti VEGF) intravitreal therapy in the first 12 weeks after VTP.

All subjects will have a 52 weeks safety follow up telephone call. (Not for AEs collection).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75004
    • Hôtel Dieu de Paris Hospital
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins,Wilmer Eye Institute
  • South Carolina
    • West Columbia, South Carolina, United States, 29169
      • Palmetto Retina Center
  • Texas
    • Harlingen, Texas, United States, 78550
      • Valley Retina 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:

• Twenty eight days or more after at least one ranibizumab injection, recurrent leakage on Fluorescein Angiography (FA) from subfoveal Choroidal NeoVessels (CNV) secondary to AMD.
• Total lesion size not exceeding 5400 μm in its greatest linear dimension.
• Best Corrected Visual Acuity (BCVA) letter score of 73 to 23 in the study eye at a starting distance of 4 meters.
• No contraindication to intravitreal ranibizumab injection.
• Postmenopausal for at least 12 months prior to enrollment or practicing medically acceptable form of birth control and not pregnant. Male subjects must be practicing a medically acceptable form of birth control.

Exclusion Criteria:

• Prior treatments:

  • Previous subfoveal laser photocoagulation, external-beam radiation therapy, or transpupillary thermoTherapy (TTT) in the study eye at any time.
  • Using anti-VEGF therapies for other indications (e.g., cancer) in the 30 days prior to the study and/or during the study
  • Received anti-VEGF injection in study eye during less than 28 days prior to Day 1 of the study.
  • More than three previous photodynamic therapy (PDT) treatments in the preceding 12 months.
  • Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within the preceding month.
  • History of vitrectomy,of glaucoma filtering surgery,submacular surgery or other surgical intervention in the study eye.
  • History of corneal transplant in the study eye.
  • Previous participation in any studies of investigational drugs within 1 month preceding Day 1 (excluding vitamins and minerals).

• Lesion Characteristics

  • Permanent structural damage to the center of the fovea of the study eye, or a concurrent ocular or systemic condition that could contraindicate administration of an investigational drug, or render the subject at a high risk of treatment complications.
  • Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either ≥50% of the total lesion area or ≥1 disc area in size.
  • Subfoveal fibrosis or atrophy in the study eye which is at least 50% of the lesion.
  • CNV in either eye due to other causes.
  • Retinal pigment epithelial tear involving the macula in the study eye.

• Concurrent Ocular Conditions

  • Active intraocular inflammation (grade trace or above) or current vitreous hemorrhage or rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye.
  • History of idiopathic or autoimmune-associated uveitis in either eye.
  • Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
  • Aphakia or absence of the posterior capsule in the study eye.
  • Spherical equivalent of the refractive error in the study eye demonstrating more-than eight diopters of myopia.
  • Intraocular surgery (including cataract surgery) in the study eye within three months preceding Day 1.
  • Uncontrolled glaucoma in the study eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: WST11 (STAKEL); Single doses of 2.5 mg/kg of STAKEL® in combination with transpupilar illumination of the macula at escalating doses from 12.5 to 75 Joules/cm².

Drug: STAKEL; Open-label,safety and exploratory efficacy study in subjects with active CNV followed for 12 weeks.During first stage(dose escalating stage) subjects assigned to group 1 to 4 will receive a single treatment of VTP at one of three light levels and one of two Drug Light Interval (DLI).Second stage(dose confirmation)will be only initiated at a dose level in which an effect has been seen at week 1 and there is a maximum of one Dose Limiting Toxicity (DLT) out of three subject at week 5.; Other Names: WST11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs) - Number of Subjects With Eye Disorders	Adverse events (AEs) consisting in Eye disorders, related or non related were collected throughout the study.	12 week follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity	Variation from baseline to week 12 in visual acuity score using Early Treatment Diabetic Retinopathy Study (ETDRS) 4.0 meter distance acuity chart. The patient is asked to read letter on a board from a distance of 4 meters. The charts use a geometric progression in letter size from line to line. The scores range from 0 (worse outcome) to 100/100 (best outcome)	Week 12.

Collaborators and Investigators

• Sponsor: Steba Biotech S.A.
• Investigators: Study Chair: Neil Bressler, Professor, Johns Hopkins University; Principal Investigator: Victor Gonzalez, Professor, Valley Retina Institute; Principal Investigator: John Wells, Professor, Palmetto Retina Center; Principal Investigator: Francine Behar Cohen, Professor, Hotel Dieu Hospital; Principal Investigator: Adrienne Scott, Doctor, Johns Hopkins/ Wilmer Eye Institute

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): May 1, 2012
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: November 29, 2009
• First Submitted That Met QC Criteria: November 29, 2009
• First Posted (ESTIMATE): December 1, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2018
• Last Update Submitted That Met QC Criteria: September 13, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: AMD; Photodynamic therapy; Macular Degeneration; CNV; Age Related Macular Degeneration; Choroidal Neovascularization; WST11; Stakel; Vascular Targeted Photodynamic therapy; VTP
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic
• Other Study ID Numbers: CLIN905 MLT202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data are available in case report form for each patient