Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of MP0112 (a novel, potentially long acting VEGF inhibitor) in patients with wet Age Related Macular Degeneration.

Official Title
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A Phase I/II, Open-label, Non-controlled, Escalating Dose, Multicentre Clinical Trial Evaluating the Safety, Preliminary Efficacy, and Pharmacokinetics of MP0112 Injected Intravitreally in Patients With Wet Age Related Macular Degeneration (AMD)

Conditions
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Wet Age-Related Macular Degeneration

Intervention / Treatment
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* Biological: MP0112


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical signs and angiographic evidence of active primary progressive subfoveal choroidal neovascularisation (CNV), including juxtafoveal lesions that affect the fovea on FA in the study eye that is at least 50% of the total lesion area ETDRS best-corrected visual acuity of: 20/40 to 20/320 in the study eye at 4 meters Male or female age > 50 years Written informed consent prior to any study procedures Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures. Exclusion Criteria: Prior treatment with anti-VEGF therapy in the study eye, including bevacizumab, ranibizumab, or pegaptanib, as well as photodynamic therapy with verteporfin Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins Subfoveal thermal laser therapy, external-beam radiation therapy, or transpupillary thermotherapy in the study eye Extrafoveal laser coagulation treatment within 12 weeks prior to Baseline in the study eye Total lesion size > 20mm2 (including blood, scars and neovascularization) as assessed by FA in the study eye Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 2.54mm2 or more in size in the study eye Scar or fibrosis, making up > 50% of total lesion in the study eye Scar, fibrosis, or atrophy involving the center of the fovea Presence of retinal pigment epithelial tears or rips History of any vitreous hemorrhage within 4 weeks prior to Visit 1 or current hemorrhage in the study eye Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye History or clinical evidence of diabetic retinopathy, diabetic macular oedema or any other vascular disease affecting the retina, other than AMD, in either eye Prior vitrectomy in the study eye History of retinal detachment or treatment or surgery for retinal detachment in the study eye Ocular surgery (including cataract removal) in the study eye within 3 months of enrolment Active intraocular inflammation (grade trace or above) in the study eye History of allergy to any components of the study drug or diagnostic devices, such as fluorescein Advanced glaucoma or intraocular pressure above 22 mmHg in the study eye despite treatment Inability to obtain fundus photographs or fluorescein angiogram of sufficient quality to be analyzed and graded by the central reading center 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 Presence of a non-healing wound, ulcer, fracture or any other medical condition associated with bleeding Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of enrolment Premenopausal women Any disorder or condition that contraindicates the use of an investigational drug Participation in another investigational drug study within 3 months of enrolment Uncontrolled hypertension Previous stroke within 12 months of study entry Systemic treatment with any anti-VEGF drug Current treatment for active systemic infection

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP0112 (0.04 mg)<br>Single 0.04 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.15 mg)<br>Single 0.15 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (0.4 mg)<br>Single 0.4 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (1.0 mg)<br>Single 1.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (2.0 mg)<br>Single 2.0 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|
| Experimental: MP0112 (3.6 mg)<br>Single 3.6 mg intravitreal injection of MP0112 in the study eye. | Biological: MP0112<br>* Single intravitreal injection of MP0112 in the study eye.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Tolerated Dose (MTD) Following a Single Injection | MTD was defined as one dose level below the lower of the dose level in which a severe (sight-threatening) drug-related Adverse Event occurred or the dose level at which more than 2 patients experienced a moderate ocular (eye) drug-related toxicity. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Stable or Improved Best Corrected Visual Acuity (BCVA) | BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 4. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision. Stable or Improved BCVA was defined as a loss of <15 letters read correctly compared to Baseline. | Baseline, Week 4 | 
| Change From Baseline in Central Area Retinal Thickness | Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Week 4. A negative change from Baseline indicated improvement (less retinal thickness). A positive change from Baseline indicated worsening (definite retinal thickening). | Baseline, Week 4 | 
| Area of Leakage as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye 10 minutes after fluorescein application at Baseline and Week 4. A lower number indicated a smaller area of leakage. | Baseline, Week 4 | 
| Area of Lesion as Measured by Fluorescein Angiography | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye after fluorescein application at Baseline and Week 4. A lower number indicated a smaller lesion area. | Baseline, Week 4 | 
| Maximum Serum Concentration (Cmax) of MP0112 at Day 3 | Blood samples were collected for MP0112 levels on Day 3. The serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory and were analyzed for MP0112 levels using an enzyme-linked immunosorbent assay. Maximum concentration at Day 3 was calculated. | Day 3 | 
| Number of Participants With Positive Binding Anti-MP0112 Antibodies | Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay. | 12 weeks |