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

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

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.

Study Overview

• Status: Completed
• Conditions: Choroidal Neovascularization; Myopia, Degenerative
• Intervention / Treatment: Drug: Combretastatin A-4 Phosphate

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 36 mg/m2 Combretastin A-4 Phosphate	Drug: Combretastatin A-4 Phosphate; 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.; Other Names: CA4P; fosbretabulin
Experimental: 45 mg/m2 Combretastatin A-4 Phosphate	Drug: Combretastatin A-4 Phosphate; 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.; Other Names: CA4P; fosbretabulin
Experimental: 27 mg/m2 Combretastatin A-4 Phosphate	Drug: Combretastatin A-4 Phosphate; 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.; Other Names: CA4P; fosbretabulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Mateon Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: August 22, 2011
• First Submitted That Met QC Criteria: August 24, 2011
• First Posted (Estimate): August 25, 2011

Study Record Updates

• Last Update Posted (Estimate): November 1, 2011
• Last Update Submitted That Met QC Criteria: October 28, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: subfoveal choroidal neovascularization; pathologic myopia
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Uveal Diseases; Choroid Diseases; Refractive Errors; Metaplasia; Choroidal Neovascularization; Neovascularization, Pathologic; Myopia; Myopia, Degenerative; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Fosbretabulin; Combretastatin
• Other Study ID Numbers: MMD-213