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

• Sponsor: Steba Biotech S.A. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01021956
• Collaborator: (none)
• Enrollment: 10
• Locations: 4
• Arm: 1
• Duration (Months): 43
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration; Choroidal Neovascularization	Drug: STAKEL	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Adverse Events (AEs) - Number of Subjects With Eye Disorders [12 week follow-up]

   Adverse events (AEs) consisting in Eye disorders, related or non related were collected throughout the study.

Secondary Outcome Measures

1. Visual Acuity [Week 12.]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins,Wilmer Eye Institute	Baltimore	Maryland	United States	21287
2	Palmetto Retina Center	West Columbia	South Carolina	United States	29169
3	Valley Retina Institute	Harlingen	Texas	United States	78550
4	Hotel Dieu de Paris Hospital	Paris		France	75004

Sponsors and Collaborators

• 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steba Biotech S.A.
• ClinicalTrials.gov Identifier: NCT01021956
• Other Study ID Numbers: CLIN905 MLT202
• First Posted: Dec 1, 2009
• Last Update Posted: Sep 17, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Steba Biotech S.A.: Macular Degeneration; Age Related Macular Degeneration; Choroidal Neovascularization; AMD; CNV; WST11; Stakel; Photodynamic therapy; Vascular Targeted Photodynamic therapy; VTP
• Additional relevant MeSH terms: Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic

Study Results

Participant Flow

Arm/Group Title	Group 1a -2.5 mg/kg STAKEL - 25 J/cm²	Group 1b-2.5 mg/kg STAKEL - 12.6 J/cm²	Group 1c-2.5 mg/kg STAKEL - 18.9 J/cm²	Group 2-2.5 mg/kg STAKEL - 50 J/cm²
Arm/Group Description	2.5 mg/kg dose of STAKEL - 25 Joules/cm² of laser light at 753 nm	2.5 mg/kg dose of STAKEL -12.6 Joules/cm² of laser light at 753 nm	2.5 mg/kg dose of STAKEL -18.9 Joules/cm² of laser light at 753 nm	2.5 mg/kg dose of STAKEL - 50 Joules/cm² of laser light at 753 nm
Period Title: Overall Study
STARTED	3	3	3	1
COMPLETED	3	3	3	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Group 1a	Group 1b	Group 1c	Group 2	Total
Arm/Group Description	2.5 mg/kg - 25 Joules/cm²	2.5 mg/kg - 12.6 Joules/cm²	2.5 mg/kg - 18.9 Joules/cm²	2.5 mg/kg - 50 Joules/cm²	Total of all reporting groups
Overall Participants	3	3	3	1	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.30 (7.51)	78.3 (6.11)	81.00 (6.08)	87.00 (0)	77.60 (7.78)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 100%	1 33.3%	1 100%	5 50%
Male	3 100%	0 0%	2 66.7%	0 0%	5 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	0 0%	0 0%	0 0%	1 10%
Not Hispanic or Latino	2 66.7%	3 100%	3 100%	1 100%	9 90%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The safety analysis set included all subjects with a signed informed consent form who received study treatment

Arm/Group Title	Group 1a	Group 1b	Group 1c	Group 2	Overall
Arm/Group Description	2.5 mg/kg - 25 Joules/cm²	2.5 mg/kg - 12.6 Joules/cm²	2.5 mg/kg - 18.9 Joules/cm²	2.5 mg/kg - 50 Joules/cm²	All doses of TOOKAD Soluble and Laser Light
Measure Participants	3	3	3	1	10
Number [participants]	3 100%	1 33.3%	0 0%	1 100%	5 50%

2. Secondary Outcome

Title	Visual Acuity
Description	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)
Time Frame	Week 12.

Outcome Measure Data

Analysis Population Description

Although STAKEL® VTP procedure induced effective neovessels occlusion in some patients, as observed in the previous study (study MLT 2.01 ), due to the small number of patients treated and the early termination of the study, limited efficacy data is available and no efficacy conclusion can be drown from this study.

Arm/Group Title	Group 1a	Group 1b	Group 1c	Group 2
Arm/Group Description	2.5 mg/kg - 25 Joules/cm²	2.5 mg/kg - 12.6 Joules/cm²	2.5 mg/kg - 18.9 Joules/cm²	2.5 mg/kg - 50 Joules/cm²
Measure Participants	3	3	3	1
Median (Full Range) [score on a scale]	2	-12	4	-33

3. Post-Hoc Outcome

Title	Number of Participants With Any Ocular or Non-ocular Adverse Events
Description	Global safety assessment including record of all complications and AEs, loss of lines in BCVA, slit lamp findings, IOP(Intra Occular Pressure), and fundus findings. All ocular and non-ocular AEs must be assessed for severity and relationship to the investigational product. Of note: the primary end point only concern patient with eye disorders events.
Time Frame	Day 1;Week 1;Week 5;Week 12.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1a	Group 1b	Group 1c	Group 2
Arm/Group Description	2.5 mg/kg - 25 Joules/cm²	2.5 mg/kg - 12.6 Joules/cm²	2.5 mg/kg - 18.9 Joules/cm²	2.5 mg/kg - 50 Joules/cm²
Measure Participants	3	3	3	1
Number [participants]	3 100%	1 33.3%	0 0%	1 100%

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	systematic Assessment : Regular investigator assessment
Arm/Group Title	Group 1A		Group 1B		Group 1C		Group 2
Arm/Group Description	2.5 mg/kg - 25 Joules/cm²		2.5 mg/kg - 12.6 Joules/cm²		2.5 mg/kg - 18.9 Joules/cm²		2.5 mg/kg - 50 Joules/cm²
All Cause Mortality
	Group 1A		Group 1B		Group 1C		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1A		Group 1B		Group 1C		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/1 (100%)
Eye disorders
retinal vascular occlusion	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	1
Other (Not Including Serious) Adverse Events
	Group 1A		Group 1B		Group 1C		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		1/3 (33.3%)		0/3 (0%)		1/1 (100%)
Eye disorders
eye pain	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Visual Acuty reduced	2/3 (66.7%)	2	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Conjunctival haemorrhage	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Ocular hyperaemia	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
Retinal pigment epitheliopathy	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0	0/1 (0%)	0
macular ischaemia	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/1 (100%)	1
Retinal haemorrhage	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2
Retinal oedema	0/3 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/1 (100%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.