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

Choroidal Neovascularization Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01423149
• Other study ID #: MMD-213
• Status: Completed
• Phase: Phase 2
• First received: August 22, 2011
• Last updated: October 28, 2011
• Start date: March 2005
• Est. completion date: January 2007

Study information

• Verified date: October 2011
• Source: OXiGENE
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Choroidal Neovascularization
• Myopia
• Myopia, Degenerative
• Neovascularization, Pathologic

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
OXiGENE

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual acuity line change from baseline at 3-month following		from baseline to 3 months	No
Primary	Visual acuity response category at 3-month follow-up		from baseline to 3 months	No
Secondary	Visual acuity line change from baseline at 1 month follow-up		from baseline to 1 month	No
Secondary	Visual acuity response category at 1 month follow-up		from baseline to 1 month	No
Secondary	Number of patients with treatment emergent adverse events		from first dose of study drug to 30 days after last dose of study drug	Yes