Safety and Efficacy Study of Combretastatin A4 Phosphate to Treat Patients With Choroidal Neovascularization Secondary to Pathologic Myopia
Primary Purpose
Choroidal Neovascularization, Myopia, Degenerative
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Combretastatin A-4 Phosphate
Sponsored by
About this trial
This is an interventional treatment trial for Choroidal Neovascularization focused on measuring subfoveal choroidal neovascularization, pathologic myopia
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
36 mg/m2 Combretastin A-4 Phosphate
45 mg/m2 Combretastatin A-4 Phosphate
27 mg/m2 Combretastatin A-4 Phosphate
Arm Description
Outcomes
Primary Outcome Measures
Visual acuity line change from baseline at 3-month following
Visual acuity response category at 3-month follow-up
Secondary Outcome Measures
Visual acuity line change from baseline at 1 month follow-up
Visual acuity response category at 1 month follow-up
Number of patients with treatment emergent adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01423149
Brief Title
Safety and Efficacy Study of Combretastatin A4 Phosphate to Treat Patients With Choroidal Neovascularization Secondary to Pathologic Myopia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
January 2007 (Actual)
Study Completion Date
January 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mateon Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroidal Neovascularization, Myopia, Degenerative
Keywords
subfoveal choroidal neovascularization, pathologic myopia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
36 mg/m2 Combretastin A-4 Phosphate
Arm Type
Experimental
Arm Title
45 mg/m2 Combretastatin A-4 Phosphate
Arm Type
Experimental
Arm Title
27 mg/m2 Combretastatin A-4 Phosphate
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Combretastatin A-4 Phosphate
Other Intervention Name(s)
CA4P, fosbretabulin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Visual acuity line change from baseline at 3-month following
Time Frame
from baseline to 3 months
Title
Visual acuity response category at 3-month follow-up
Time Frame
from baseline to 3 months
Secondary Outcome Measure Information:
Title
Visual acuity line change from baseline at 1 month follow-up
Time Frame
from baseline to 1 month
Title
Visual acuity response category at 1 month follow-up
Time Frame
from baseline to 1 month
Title
Number of patients with treatment emergent adverse events
Time Frame
from first dose of study drug to 30 days after last dose of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Study of Combretastatin A4 Phosphate to Treat Patients With Choroidal Neovascularization Secondary to Pathologic Myopia
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