Macugen for Proliferative Diabetic Retinopathy Study With Extended Dosing (M-PDRS ED)

A Pilot Study to Determine if Intravitreal Injections of Pegaptanib Sodium (Macugen) Given Every 12 Weeks for a Year After an Induction Phase of Three Injections Every 6 Weeks Will Reduce the Progression of Proliferative Diabetic Retinopathy in Patients Without Significant Vitreous Hemorrhage in Comparison to Treatment With Retinal Photocoagulation Alone and After an Induction Phase

Intravitreal injections of pegaptanib will induce the regression of Proliferative Diabetic Retinopathy (PDR) and reduce the need for retinal photocoagulation.

Study Overview

• Status: Unknown
• Conditions: Proliferative Diabetic Retinopathy
• Intervention / Treatment: Drug: Macugen ® (pegaptanib sodium)

Detailed Description

Primary Objective:

To further establish the efficacy of intravitreal pegaptanib injections in the regression of retinal neovascularization secondary to high-risk PDR, as compared to standard panretinal photocoagulation (PRP)

Secondary Objective:

To maintain the regression of PDR after the induction phase with intravitreal pegaptanib injections administered at 12-week intervals, as compared to standard PRP

To maintain the regression of PDR after the induction phase with retinal photocoagulation applied to areas of ischemia (Selective Laser Photocoagulation), as compared to standard PRP

To evaluate the rate of recurrence of neovascularization after 6 intravitreal pegaptanib injections

To determine if intravitreal pegaptanib will reduce the area and/or volume of concomitant diabetic macular edema, as assessed by leakage on fluorescein angiography (FA) and/or optical coherence tomography (OCT)

To determine if intravitreal pegaptanib injections maintain or reduce the loss of best-corrected visual acuity

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • McAllen, Texas, United States, 78503
      • Valley Retina Insitute, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Eligible eyes will have active PDR with high risk characteristics (HRC) as defined by the DRS. All eyes must meet at least one or both of the following criteria:

   • Mild neovascularization of the disc (NVD) of at least 1/4 to 1/3 disc area as shown in standard photograph 10A of the DRS.
   • Moderate neovascularization of the retina elsewhere (NVE) of at least 1/2 disc area as shown in standard photograph 7 of the DRS.
2. ETDRS visual acuity score greater than or equal to 24 letters (approximately 20/320) and less than or equal to 85 letters (approximately 20/20) by the ETDRS visual acuity protocol at the screening visit.
3. Eyes with mild pre-retinal hemorrhage (PRH) or mild vitreous hemorrhage (VH) that does not interfere with clear visualization of the macula and optic disc are eligible for this study.
4. Evaluating physician believes that PRP can be safely withheld for 3 weeks.

Exclusion Criteria:

1. Presence of moderate or dense PRH or VH that prevents clear visualization of the macula and/or optic disc.

2. Presence of either:

   • significant epiretinal membranes involving the macula, OR

   • proliferative diabetic membranes along the major retinal arcades that are extensive enough to cause either:

     • significant vitreomacular traction, OR
     • significant impairment in visual acuity.
3. Presence of any tractional retinal detachment.
4. Severe ischemia involving the foveal avascular zone as determined by fluorescein angiography performed at the initial screening visit.
5. Significant media opacity (due to cornea, anterior chamber, or lens) precluding clear visualization of the macula or optic disc.
6. Presence of neovascular glaucoma with or without hyphema.
7. Previous treatment with intravitreal steroid injections in the study eye within 6 months of baseline.
8. Previous treatment with peribulbar steroid injections in the study eye within 90 days of baseline
9. Previous PRP laser treatment in the study eye within 90 days of baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV Macugen Q6; Will receive 3 intravitreal pegaptanib injections at 6-week intervals, then 3 additional injections at 12-week intervals	Drug: Macugen ® (pegaptanib sodium); Patients assigned to either IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. The group will then receive an intravitreal injection every 12 weeks. Patients assigned to IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. After the third injection subjects in this group will receive Selective Laser Photocoagulation at Week 18. Patients assigned to Panretinal Photocoagulation will act as the control group. Subjects in this group will receive standard Panretinal Photocoagulation using a modified ETDRS protocol. All intravitreal study injections will consist of 0.3 milligrams (mg) of pegaptanib sodium delivered by intravitreal injection.
Experimental: IV Mac Q6 Arm; Will Selective Laser Photocoagulation after 3 intravitreal pegaptanib injections	Drug: Macugen ® (pegaptanib sodium); Patients assigned to either IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. The group will then receive an intravitreal injection every 12 weeks. Patients assigned to IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. After the third injection subjects in this group will receive Selective Laser Photocoagulation at Week 18. Patients assigned to Panretinal Photocoagulation will act as the control group. Subjects in this group will receive standard Panretinal Photocoagulation using a modified ETDRS protocol. All intravitreal study injections will consist of 0.3 milligrams (mg) of pegaptanib sodium delivered by intravitreal injection.
Experimental: Pan Retinal Photocoagulation; Will act as the control group, thus subjects in this group will receive standard PRP (modified ETDRS protocol)	Drug: Macugen ® (pegaptanib sodium); Patients assigned to either IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. The group will then receive an intravitreal injection every 12 weeks. Patients assigned to IV Mac Q6Arm will receive a total of 3 intravitreal pegaptanib sodium injections administered at 6-week intervals beginning on Day 0 and ending at Week 12. After the third injection subjects in this group will receive Selective Laser Photocoagulation at Week 18. Patients assigned to Panretinal Photocoagulation will act as the control group. Subjects in this group will receive standard Panretinal Photocoagulation using a modified ETDRS protocol. All intravitreal study injections will consist of 0.3 milligrams (mg) of pegaptanib sodium delivered by intravitreal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish efficacy of intravitreal pegaptanib sodium injections in causing regression of high risk proliferative diabetic retinopathy as compared to panretinal photocoagulation	To assess the efficacy of intravitreal pegaptanib sodium injections in inducing regression of high risk PDR (as determined by percentage of eyes without treatment failure) using standard panretinal photocoagulation (PRP) as the control arm. Treatment failure is defined as: Development of increased NVD and/or NVE; NVD and/or NVE that is not regressed at least 50% compared to the baseline amount within 3 weeks; Development of significant vitreous hemorrhage that is sufficient in quantity to obscure visualization of the entire macula, optic disc, and the major temporal arcade vessels	54 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the efficacy of intravitreal pegaptanib injections in preventing the loss of best corrected visual acuity	To determine if intravitreal pegaptanib sodium injections maintain or reduce the loss of best-corrected visual acuity as measured by comparing the percentages of patients that lost 3 or more lines on ETDRS chart in the study arms.	54 weeks

Collaborators and Investigators

• Sponsor: Valley Retina Institute
• Collaborators: Pfizer
• Investigators: Principal Investigator: Victor H. Gonzalez, MD, Valley Retina Insitute

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Anticipated): August 1, 2013
• Study Completion (Anticipated): February 1, 2014

Study Registration Dates

• First Submitted: December 2, 2011
• First Submitted That Met QC Criteria: December 5, 2011
• First Posted (Estimate): December 6, 2011

Study Record Updates

• Last Update Posted (Estimate): December 6, 2011
• Last Update Submitted That Met QC Criteria: December 5, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Proliferative Diabetic Retinopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy
• Other Study ID Numbers: MPDRS-ED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No