Choroidal Neovascularization, Macular Degeneration
Conditions
Keywords
Macular Degeneration, Age Related Macular Degeneration, Choroidal Neovascularization, AMD, CNV, WST11, Stakel, Photodynamic therapy, Vascular Targeted Photodynamic therapy, VTP
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).
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).
Interventions
DRUGSTAKEL
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.
Sponsors
Steba Biotech S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1a 2.5 mg/kg - 25 Joules/cm² | 3 |
| Group 1b 2.5 mg/kg - 12.6 Joules/cm² | 3 |
| Group 1c 2.5 mg/kg - 18.9 Joules/cm² | 3 |
| Group 2 2.5 mg/kg - 50 Joules/cm² | 1 |
| Total | 10 |
Baseline characteristics
| Characteristic | Total | Group 1a | Group 1b | Group 1c | Group 2 |
|---|---|---|---|---|---|
| Age, Continuous | 77.60 years STANDARD_DEVIATION 7.78 | 70.30 years STANDARD_DEVIATION 7.51 | 78.3 years STANDARD_DEVIATION 6.11 | 81.00 years STANDARD_DEVIATION 6.08 | 87.00 years STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 1 / 3 | 0 / 3 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 0 / 3 | 1 / 1 |
Outcome results
Primary
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.
Time frame: 12 week follow-up
Population: The safety analysis set included all subjects with a signed informed consent form who received study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1a | Adverse Events (AEs) - Number of Subjects With Eye Disorders | 3 participants |
| Group 1b | Adverse Events (AEs) - Number of Subjects With Eye Disorders | 1 participants |
| Group 1c | Adverse Events (AEs) - Number of Subjects With Eye Disorders | 0 participants |
| Group 2 | Adverse Events (AEs) - Number of Subjects With Eye Disorders | 1 participants |
| Overall | Adverse Events (AEs) - Number of Subjects With Eye Disorders | 5 participants |
Secondary
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)
Time frame: Week 12.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1a | Visual Acuity | 2 score on a scale |
| Group 1b | Visual Acuity | -12 score on a scale |
| Group 1c | Visual Acuity | 4 score on a scale |
| Group 2 | Visual Acuity | -33 score on a scale |
Post Hoc
Number of Participants With Any Ocular or Non-ocular Adverse Events
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1a | Number of Participants With Any Ocular or Non-ocular Adverse Events | 3 participants |
| Group 1b | Number of Participants With Any Ocular or Non-ocular Adverse Events | 1 participants |
| Group 1c | Number of Participants With Any Ocular or Non-ocular Adverse Events | 0 participants |
| Group 2 | Number of Participants With Any Ocular or Non-ocular Adverse Events | 1 participants |