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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
OXiGENE
ClinicalTrials.gov Identifier:
NCT01423149
First received: August 22, 2011
Last updated: October 28, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Choroidal Neovascularization
Myopia, Degenerative
Drug: Combretastatin A-4 Phosphate
Phase 2

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

Further study details as provided by OXiGENE:

Primary Outcome Measures:
  • Visual acuity line change from baseline at 3-month following [ Time Frame: from baseline to 3 months ] [ Designated as safety issue: No ]
  • Visual acuity response category at 3-month follow-up [ Time Frame: from baseline to 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Visual acuity line change from baseline at 1 month follow-up [ Time Frame: from baseline to 1 month ] [ Designated as safety issue: No ]
  • Visual acuity response category at 1 month follow-up [ Time Frame: from baseline to 1 month ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: March 2005
Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: OXiGENE
ClinicalTrials.gov Identifier: NCT01423149     History of Changes
Other Study ID Numbers: MMD-213
Study First Received: August 22, 2011
Last Updated: October 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by OXiGENE:
subfoveal choroidal neovascularization
pathologic myopia

Additional relevant MeSH terms:
Myopia
Neovascularization, Pathologic
Myopia, Degenerative
Choroidal Neovascularization
Refractive Errors
Eye Diseases
Metaplasia
Pathologic Processes
Choroid Diseases
Uveal Diseases
Combretastatin
Combretastatin A-4
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014