Combretastatin A4 Phosphate in Patients With Neovascular Age-Related Macular Degeneration

NCT01570790 | Completed Phase 1

• 1 other identifier: FBO-206
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is assess safety, bioactivity, and maximal tolerated dose of repeated weekly intravenous infusion of combretastatin A-4 phosphate (CA4P) in patients with neovascular age-related macular degeneration

Conditions

Combretastatin A4 Phosphate; Age-related Macular Degeneration; AMD; CNV; Choroidal Neovascularization

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  To report frequency and severity of adverse events, as defined by the common terminology criteria of adverse events (CTCAE v.3.0; National Cancer Institute), and to determine the degree of relationship of adverse events to the study drug (CA4P).

  12 weeks after the first infusion of the Study Drug

• Dose Limiting Toxicities (DLT)

  DLT is defined as any of the following adverse events if ≥Grade-2 in severity: ventricular arrhythmia, second or third degree AV block, severe sinus bradycardia \< 45 bpm, tachycardia \>120 bpm, supraventricular arrhythmia \> 24 hours, ventricular tachycardia (\>9 beats in a row), any length of torsades de pointes, unexplained recurrent syncope, QTc prolongation ≥500 msec on \> 2 consecutive ECGs, Grade-2 or greater myocardial infarction, or ocular toxicities deemed by the investigator not acceptable for the patients to receive further treatments.

  12 weeks after the first infusion of the study drug

Secondary Outcomes (3)

• Maximum Tolerated Dose

  12 weeks after the first infusion of the study drug

• Change in Best Corrected Visual Acuity

  4 and 12 weeks after first infusion of the study drug

• Change in Central Retinal Thickness

  4 and 12 weeks following the first infusion of CA4P

Study Arms (3)

Cohort 1

EXPERIMENTAL

Drug: Combretastatin A-4 phosphate

Cohort 2

EXPERIMENTAL

Drug: Combretastatin A-4 Phosphate

Cohort 3

EXPERIMENTAL

Drug: Combretastatin A-4 Phosphate

Interventions

Combretastatin A-4 Phosphate DRUG

27 mg/m2 CA4P IV infusion at baseline and every week for 4 doses

Also known as: fosbretabulin disodium

Cohort 1

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50 years or older;
• lead electrocardiogram (ECG) performed at least 2 weeks but less than 4 weeks prior to entry into the study showing a QTc \<440 with no evidence of current or prior myocardial ischemia, infarction or significant arrhythmia as determined by review and signature of the cardiologist.
• Adequate bone marrow function:
• Absolute granulocyte count ≥1500 cells/mm3; Platelet count ≥100,000 cells/mm3; Hemoglobin ≥9.0gm/ dL;
• PT/PTT within the institution upper limit of normal (ULN) or INR \<1.1 ;
• Adequate hepatic function:
• Total bilirubin within the institution ULN; Alanine and aspartate aminotransferase (ALT/AST) \<3 times the institutional ULN;
• Adequate renal function: serum creatinine ≤2.0 mg/dL;
• Ophthalmic criteria:
• Best corrected visual acuity in the study eye of ≤20/40 and ≥20/800 in the fellow eye.
• Subfoveal choroidal neovascularization (as illustrated by fluorescein angiography) secondary to age-related macular degeneration, with a total lesion size of ≤12 total disc areas, of which at least 50% must be active CNV.
• Subretinal hemorrhage ≤50% of total lesion size;
• For patients with minimally classic and purely occult CNV, there must be documented evidence of ≥2 lines of vision loss (ETDRS) during the previous 12 weeks;
• Clear ocular media and adequate papillary dilatation to permit good quality stereoscopic fundus photography;
• Male fertile patients must abstain from sexual intercourse or use effective birth control;

You may not qualify if:

• Previous subfoveal thermal laser therapy;
• Any subfoveal scarring or atrophy, or \>25% of the total lesion size is made up of scarring or atrophy;
• Significant media opacities, including cataract, which can interfere with visual acuity, assessment of toxicity, or fundus photography;
• Presence of other causes of choroidal neovascularization, including pathologic myopia (spherical equivalent of ≥-8.0 diopters, or axial length of ≥25mm), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis and other uveitic entities;
• Any condition that might interfere with assessment of the progression of CNV;
• Any intraocular surgery in the study eye within 12 weeks of screening for the study;
• Other treatment for AMD of the study eye within 12 weeks prior to screening;
• Known allergy to fluorescein;
• Any current or history of significant gastrointestinal, oral, or nasal bleeding;
• Serious intercurrent infections or other nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy;
• Grade 2 (CTC v.3.0) or greater pre-existing peripheral neuropathy;
• Psychiatric disorders or other conditions rendering patients incapable of complying with the requirements of the protocol;
• Pregnant or breast-feeding women;
• History of angina, myocardial infarction, CHF, non-controlled atrial arrhythmias or clinically significant arrhythmias including conduction abnormality, nodal junctional arrhythmias and dysrhythmias, sinus bradycardia or tachycardia, supraventricular arrhythmias, atrial fibrillation or flutter, syncope or vasovagal episodes;
• Abnormal cardiac stress test;

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Wilmer Eye Institute

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Ibrahim MA, Do DV, Sepah YJ, Shah SM, Van Anden E, Hafiz G, Donahue JK, Rivers R, Balkissoon J, Handa JT, Campochiaro PA, Nguyen QD. Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate. BMC Pharmacol Toxicol. 2013 Jan 14;14:7. doi: 10.1186/2050-6511-14-7.

  PMID: 23316779 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

fosbretabulin

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Quan D Nguyen, MD, MSc

  Wilmer Eye Institute - Johns Hopkins University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2012
• First Posted: April 4, 2012
• Study Start: May 1, 2003
• Primary Completion: June 1, 2005
• Study Completion: June 1, 2005
• Last Updated: December 6, 2017

Record last verified: 2017-12

Locations

US (1)