A Phase 2/3 Randomized, Controlled, Double-Masked, Multi-Center, Comparative Trial, in Parallel Groups, to Compare the Safety and Efficacy of Intravitreous Injections of 0.3 mg Pegaptanib Sodium (Macugen), Given as Often as Every 6 Weeks for 2 years, to Sham Injections, in Subjects with Diabetic Macular Edema (DME) Involving the Center of the Macula - N/A

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-001460-32-GR
• Date of registration: 14/06/2006
• Prospective Registration: No
• Primary sponsor: (OSI) Eyetech Pharmaceuticals, Inc.
• Public title: A Phase 2/3 Randomized, Controlled, Double-Masked, Multi-Center, Comparative Trial, in Parallel Groups, to Compare the Safety and Efficacy of Intravitreous Injections of 0.3 mg Pegaptanib Sodium (Macugen), Given as Often as Every 6 Weeks for 2 years, to Sham Injections, in Subjects with Diabetic Macular Edema (DME) Involving the Center of the Macula - N/A
• Scientific title: A Phase 2/3 Randomized, Controlled, Double-Masked, Multi-Center, Comparative Trial, in Parallel Groups, to Compare the Safety and Efficacy of Intravitreous Injections of 0.3 mg Pegaptanib Sodium (Macugen), Given as Often as Every 6 Weeks for 2 years, to Sham Injections, in Subjects with Diabetic Macular Edema (DME) Involving the Center of the Macula - N/A
• Date of first enrolment: 27/02/2006
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-001460-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Sham Injection

Countries of recruitment

Belgium, Czech Republic, Denmark, Germany, Greece, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
OPHTHALMIC CRITERIA

Subjects must have macular edema that involves the center of the macula with corresponding leakage on fluorescein angiogram. Leakage will be confirmed retrospectively by the IRC.

Foveal thickness of at least 250 microns (OCT center point thickness), with a standard deviation of the center point of <10%, an OCT signal strength of ? 5 is recommended, and properly created ILM and RPE borders at Baseline by computer software. In cases that the OCT image software fails to properly draw ILM and RPE borders, if the IRC obtains a manual estimate of OCT center point thickness of at least 250 microns, then the patient will be considered eligible.

Best corrected distance visual acuity in the study eye must be a letter score between 65 and 35 inclusive (20/50 to 20/200 Snellen equivalents).

Clear ocular media and adequate pupillary dilatation to permit good quality stereoscopic fundus photography.

Intraocular pressure of 21 mmHg, or less.

The treating ophthalmologist should be comfortable that focal laser (direct and grid as needed) can be deferred for at least 18 weeks in the study eye, even though focal or grid laser is indicated.


GENERAL CRITERIA

Type I, or Type II diabetic subjects as defined by the WHO criteria. (See Appendix 15.11), of either gender, and aged = 18 years .

Performance Status = 2 according to the Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale. (See Appendix 15.6)

Normal electrocardiogram (ECG), or clinically non-significant changes.

Women must be using effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile. All women of childbearing potential must have a negative serum pregnancy test at baseline and negative urine pregnancy tests immediately prior to each injection and use two effective forms of contraception during the trial and for at least 60 days following the last dose of pegaptanib sodium.

Adequate hematological function: hemoglobin =10 g/dL; platelet count =130 x 109/l; WBC = 3.8 x 109/l.

Adequate liver function: serum bilirubin =1.5 mg/dL; SGOT/ALT, SGPT/AST, GGT and alkaline phosphatase within 2 x ULN.

Adequate renal function: serum creatinine = 2.5 mg/dL and BUN within 2.5 x ULN.

Ability to provide written informed consent.

Ability to return for all trial visits.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects will not be eligible for the trial if any of the following criteria are present systemically, or in the study eye:

Eyes with prior scatter (panretinal) photocoagulation less than 6 months prior to baseline angiography/photography or eyes in which scatter (panretinal) photocoagulation is needed now or is likely to be needed within the next 9 months (e.g. eyes with DRS high risk PDR not already adequately treated with photocoagulation).

Presence of any abnormality that is likely to confound assessment of visual acuity improvement in eyes in which macular edema resolves, or improves, such as non-perfusion for >1 disc area involving the foveal avascular zone (FAZ - involving 2 or more quadrants centered around the foveal avascular zone), epiretinal membrane associated with signs of contraction and/or significant opacification (i.e. striae within 1 disc diameter of the foveal center), or presence of chorioretinal atrophy involving the center of the macula.

Vitreomacular traction determined clinically and/or by OCT, which, in the investigator’s opinion, contributes to the macular edema (or causes associated foveal detachment), and would preclude improvement with pegaptanib sodium or sham treatment.

Any other cause of macular edema such as vitreous extension, or entrapment to anterior segment wound, or any retinal vein occlusion involving the macula.

Atrophy/scarring/fibrosis involving the center of the macula, including evidence of laser treated atrophy within 200 microns of FAZ.

Any subfoveal hard exudates, or RPE atrophy (by fundus examination, fundus photograph, FA or OCT).

Subjects who have received YAG laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only), or focal or grid photocoagulation, within the previous 16 weeks.

Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity or fundus photography. Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 1 year.

Any intraocular surgery within 6 months of trial entry.

Previous vitrectomy.

HbA1C level >10% or recent signs of uncontrolled diabetes (3 or more episodes of severe hypoglycemia by DCCT (Diabetes Control and Complications Trial) definition [10] within 3 months of baseline, or 2 or more episodes of ketoacidosis within 1 year of baseline, or an episode of ketoacidosis within 3 months of baseline).

Any of the following underlying systemic diseases including:
•History or evidence of severe cardiac disease, e.g. NYHA Functional Class III or IV (Appendix 15.7), clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrythmias requiring ongoing treatment.
•History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation.
•Clinically significant impaired renal function (serum creatinine >2.5 mg/dL or s/p renal transplant or receiving dialysis).
•Clinically significant impaired hepatic function.
•Stroke (within 12 months of trial entry).
•Any major surgical procedure within one month of trial entry.

Previous radiation to the head in the region of the study eye.

Any of the following prior treatments or at anytime during the study:
•Investigational agents for DME (including intravitreal, subconjunctival or subtenons corticosteroid

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetic Macular Edema (DME)
MedDRA version: 8.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema

Intervention(s)

Trade Name: Macugen
Product Code: EYE001
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Pegaptanib Sodium
CAS Number: 222716-86-1
Current Sponsor code: EYE001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.3-
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Intraocular use

Primary Outcome(s)

Main Objective: The objective of this trial will be to confirm the safety and compare the efficacy of pegaptanib sodium when subjects are given intravitreous injections of 0.3 mg/eye versus sham injections in a 1:1 ratio, respectively. All subjects previously randomized to the 0.03 or 0.003 mg/eye treatment arms during the conduct of EOP1013 through EOP1013C will be given the option of either receiving injections of 0.3 mg/eye or withdrawing from the study. Injections will be given as often as every 6 weeks for 2 years, in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia.

Primary end point(s): The proportion of subjects exhibiting an improvement of = 10 letters (or 2-lines) of vision (ETDRS) from baseline.

Secondary Objective: N/A

Secondary ID(s)

N/A

EOP1013D

2005-001460-32-IT