Phase II Clinical Trial of Intravenous Combretastatin A4 Phosphate in Patients With Subfoveal Choroidal Neovascular Membranes (CNV) in Pathologic Myopia

Abstract

 

Purpose:

 

To investigate/evaluate the safety & efficacy of CombretastatinA4 Phosphate (CA4P), a vascular disrupting agent, for treatingsubfoveal CNV in subjects with pathologic myopia.

 

Methods:

 

This Phase II, parallel group, dose-ranging, double masked studyconducted in 9 centers in North America, Taiwan and Russia enrolledsubjects into one of three treatment groups (27, 36, or 45 mg/m²).Subjects received two IV infusions of CA4P one week apart perprotocol. During follow-up visits, subjects could receive upto three additional re-treatments. Primary efficacy endpointis best corrected ETDRS at 3 months with less than 3 lines ofvision loss. Safety variables include vital signs, physicalexams, laboratory tests, slit-lamp biomicroscopy, dilated fundusexams, fundus photography, ECGs, and adverse events (AEs).

 

Results:

 

By June 2006, 21 subjects (7 subjects into each dose group)were enrolled at 9 study centers. Of these, 13 completed theETDRS 3 month assessment (27 mg/m² n=5; 36 mg/m² n= 4; 45 mg/m²n=4). The primary endpoint data suggests a possible dose responserelationship (Table 1). Vision was maintained in all patientsin all dose groups. Trends in FA and OCT data were not observedand are inconclusive at this time.Table 1: Best corrected visualacuity results at 3 months by dose of CA4PTable 2: AE’s Possibly related to StudyDrug by Severity 

 

 

Conclusions:

 

Preliminary data suggests a beneficial effect of CA4P’snovel mechanism of action as a vascular disrupting agent forCNV, and supports further development of oral and topical formsof administration for diseases associated with CNV. Final datafor all patients will be available and presented in May 2007.

 

Clinical Trial:

 

www.clinicaltrials.gov ISRCTN85551991

 

Keywords: choroid: neovascularization • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials