Safety and Efficacy Study of Combretastatin A4 Phosphate to Treat Patients With Choroidal Neovascularization Secondary to Pathologic Myopia

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the safety and efficacy of 3 dose groups (27, 36 and 45 mg/m2) of Combretastatin A-4 Phosphate for the treatment of subfoveal choroidal neovascularization in subjects with pathologic myopia.

Official Title
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A Phase II, Dose Ranging, Multi-Center Study to Evaluate the Safety and Efficacy of Combretastatin A4 Phosphate for Treating Subfoveal Choroidal Neovascularization in Subjects With Pathologic Myopia

Conditions
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Choroidal Neovascularization, Myopia, Degenerative

Intervention / Treatment
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* Drug: Combretastatin A-4 Phosphate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Be able and willing to follow instructions Age 18 to 50 years old (inclusive) Have area of CNV within 50 um or under the geometric center of the foveal avascular zone Have greatest linear dimension of lesion 5,400 um or less, with >/=50.0% of the lesion composed of CNV (features which obscure the boundaries of the CNV such as blood, serous pigment epithelial detachment or blocked fluorescence must occupy <50.0%) as confirmed by Doheny Image Reading Center (DIRC) Have best corrected distance visual acuity (ETDRS) of 20/20 to 20/200 (LogMAR +0.0 to 1.0), inclusive in the qualifying eye(s) Have pathologic myopia presenting - 6.0 diopters or more correction required OR an axial length of the >/= 26.5 mm Be able and willing to avoid any medication that the investigator feels may interfere with the study If female and of childbearing potential, agree to submit a sample for pregnancy testing and have a negative pregnancy test within 1 day prior to each treatment. Females are considered of childbearing potential unless they are surgically sterile or post-menopausal for 12 months. Females of childbearing potential must agree to an approved form of contraception for the duration of the study. Exclusion Criteria: Have contraindications, allergies or sensitivity to the use of the study medications Have clinical signs or symptoms, in the opinion of the investigator, that may interfere with the study Features of any condition other than pathologic myopia associated with CNV, such as age-related macular degeneration Have a tear of the retinal pigmented epithelium Have undergoing ocular therapy/surgery or major surgery in the last 3 months or have any surgeries planned during the study period Have any significant illness or condition, ocular or systemic that could, in the opinion of the investigator, be expected to interfere with the study Have angina (stable or severe, even if controlled with medications), 6 months S/P myocardial infarction ,congestive heart failure, history of or presence of any clinically significant supraventricular or ventricular arrhythmias or syncope episodes Have ECG with QTc >450 msdec or other clinically significant abnormalities such as left bundle branch block, left ventricular hypertrophy, etc. Have uncontrolled QTc prolongation Take any drugs known to prolong the QTc interval however subject can remain eligible if a non-QTc substitute can be administered Have uncontrolled hypertension (defined as blood pressure consistently greater than 150/100 mm Hg irrespective of medication) Uncontrolled hypokalemia and/or hypomagnesemia Have symptomatic peripheral vascular disease or cerebrovascular disease Have psychiatric disorders or other conditions rendering subjects incapable of complying with the requirements of the protocol Be receiving concurrent hormonal therapy with exception of Gonadotropin-releasing hormone agonists in subjects with hormone refractory prostate cancer, hormone replacement therapy, oral contraceptive, and megestrol acetate used for anorexia/cachexia Be receiving anticoagulation with warfarin, heparin or low molecular weight heparin other than low dose (1 mg) warfarin for maintenance of Hickman line patency Be a woman who is currently pregnant, nursing, or planning a pregnancy; or woman who has a positive pregnancy test Have participated in an investigational drug or device trial within 30 days of entering the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 36 mg/m2 Combretastin A-4 Phosphate<br> | Drug: Combretastatin A-4 Phosphate<br>* Combretastatin A-4 Phosphate is administered on Day 0 and Day 7 (+/- 2 days). If the treating ophthalmologist notes any leakage from CNV in the study eye on a fluorescein angiography during the study or an increase in subretinal fluid on an optical coherence tomography measurement, retreatment with Combretastatin A-4 Phosphate is recommended with up to 3 additional treatments. The retreatment visit(s) could occur during a scheduled visit or at an additional visit 1 week after a regular study visit. A post-retreatment follow-up visit is necessary.<br>* Other names: fosbretabulin;|
| Experimental: 45 mg/m2 Combretastatin A-4 Phosphate<br> | Drug: Combretastatin A-4 Phosphate<br>* Combretastatin A-4 Phosphate is administered on Day 0 and Day 7 (+/- 2 days). If the treating ophthalmologist notes any leakage from CNV in the study eye on a fluorescein angiography during the study or an increase in subretinal fluid on an optical coherence tomography measurement, retreatment with Combretastatin A-4 Phosphate is recommended with up to 3 additional treatments. The retreatment visit(s) could occur during a scheduled visit or at an additional visit 1 week after a regular study visit. A post-retreatment follow-up visit is necessary.<br>* Other names: fosbretabulin;|
| Experimental: 27 mg/m2 Combretastatin A-4 Phosphate<br> | Drug: Combretastatin A-4 Phosphate<br>* Combretastatin A-4 Phosphate is administered on Day 0 and Day 7 (+/- 2 days). If the treating ophthalmologist notes any leakage from CNV in the study eye on a fluorescein angiography during the study or an increase in subretinal fluid on an optical coherence tomography measurement, retreatment with Combretastatin A-4 Phosphate is recommended with up to 3 additional treatments. The retreatment visit(s) could occur during a scheduled visit or at an additional visit 1 week after a regular study visit. A post-retreatment follow-up visit is necessary.<br>* Other names: fosbretabulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity line change from baseline at 3-month following |  | from baseline to 3 months | 
| Visual acuity response category at 3-month follow-up |  | from baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity line change from baseline at 1 month follow-up |  | from baseline to 1 month | 
| Visual acuity response category at 1 month follow-up |  | from baseline to 1 month | 
| Number of patients with treatment emergent adverse events |  | from first dose of study drug to 30 days after last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subfoveal choroidal neovascularization, pathologic myopia