A Randomized, Multi-center, Phase II Study of the Safety, Tolerability and Bioactivity of Repeated Intravitreal Injections of iCo-007 as Monotherapy or in Combination With Ranibizumab or Laser Photocoagulation in the Treatment of Diabetic Macular Edema (the iDEAL Study) (iDEAL)

A Randomized, Multi-center, Phase II Study of the Safety, Tolerability, and Bioactivity of Repeated Intravitreal Injections of iCo-007 as Monotherapy or in Combination With Ranibizumab or Laser Photocoagulation in the Treatment of Diabetic Macular Edema With Involvement of the FoveAL Center (the iDEAL Study)

• To assess the safety of repeated iCo-007 intravitreal injections in treatment of subjects with diabetic macular edema as monotherapy and in combination with ranibizumab or laser photocoagulation
• To assess the change in visual acuity and retinal thickness on optical coherence tomography (OCT) from baseline to month 8 and month 12

Study Overview

• Status: Terminated
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: iCo-007 350 mcg; Drug: iCo-007 700 mcg; Drug: iCo-007 350 mcg and Laser; Drug: Ranibizumab and iCo-007 350 mcg

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5540
      • Stanley M Truhlsen Eye Institute

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:

• Age ≥18 years
• Have diabetes mellitus type I or II (insulin or non-insulin dependent) with HbA1c ≥5.5% and HbA1c ≤13%; have non-proliferative diabetic retinopathy, or inactive proliferative diabetic retinopathy, or proliferative diabetic retinopathy with a reasonable expectation that panretinal photocoagulation will not be required during the study follow-up period
• Have diabetic macular edema with central subfield thickness of ≥250 microns (confirmed by Stratus Time-Domain(TD) OCT

• Have best corrected visual acuity (ETDRS) that is Snellen equivalent of

  • 20/32 and ≥20/320, inclusive
• Be willing and able to sign an approved written informed consent. If a patient has a central nervous system disorder (i.e. dementia) that will not allow him/her to understand the consent independently, the patient will not be allowed to join the study
• Be able to attend all scheduled study visits
• Women who are not lactating or pregnant and are willing to use adequate contraception during the study period, if appropriate

Exclusion Criteria:

• Have macular or perimacular edema secondary to an etiology other than diabetes
• Have concurrent retinal diseases other than diabetic retinopathy
• Have additional ocular diseases compromising visual acuity and/or interfering with study assessments; patients who have glaucoma but deemed stable (intraocular pressure ≤ 25 mmHg at screening) on medications or status post surgery, may participate in the study
• Participant has a history of prior pars plana vitrectomy
• Subjects with significant cataract or or posterior capsular opacification that may need intervention within one year or vitreous opacity that hinder study assessment (i.e.fundus examination) which requires intervention within a year
• Subjects who have DME with severe capillary non-perfusion (avascular zone diameter >1,000 microns)
• Have an allergy to fluorescein dye
• Have terminal renal disease (on active kidney dialysis), cerebral vascular accident(including TIA), myocardial infarction or congestive heart disease within 6 months of study enrollment, liver damage (2x upper limit of normal range for aspartate aminotransferase (AST), Alanine aminotransferase (ALT) or total bilirubin). Patients who may have received renal transplant in the past and now have stable renal function, may participate in the study
• Subjects with systolic blood pressure higher than 180 mm Hg or diastolic above 100 mm Hg, with or without anti-hypertensive treatment
• Have a history of panretinal photocoagulation (PRP) in the study eye within 3 months of study entry or are likely to have PRP in the study eye during study participation
• Had macular photocoagulation or ocular surgery within 3 months of study entry in the study eye
• Received intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry or anti-angiogenic drugs (pegaptanib sodium, ranibizumab, bevacizumab, VEGF-TRAP, protein kinase C inhibitor, etc.) within 2 months of study entry; history of usage of topical or systemic steroids within 3 months of study entry is not an exclusion

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Drug: iCo-007 350 mcg iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4	Drug: iCo-007 350 mcg; iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4; Other Names: Group 1
Experimental: Group 2; Drug: iCo-007 700 mcg iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4	Drug: iCo-007 700 mcg; iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4; Other Names: Group 2
Experimental: Group 3; Drug: iCo-007 350 mcg and Laser iCo-007 (350 μg) as an intravitreal injection at baseline followed 7 days later by laser photocoagulation. At M4, intravitreal injection of iCo-007 (350 μg) will be given as mandatory treatment. If the eye also meets retreatment criteria, it will also receive the second laser photocoagulation	Drug: iCo-007 350 mcg and Laser; iCo-007 (350 μg) as an intravitreal injection at baseline followed 7 days later by laser photocoagulation. At M4, intravitreal injection of iCo-007 (350 μg) will be given as mandatory treatment. If the eye also meets retreatment criteria, it will also receive the second laser photocoagulation; Other Names: Group 3
Experimental: Group 4; Drug: Ranibizumab and iCo-007 350 mcg Ranibizumab (0.5 mg) intravitreal injection at baseline followed by iCo-007 (350 μg) intravitreal injection 2 weeks later; re-treatment with ranibizumab (0.5 mg) mandatory at M4 followed by iCo-007 (350 μg) 2 weeks later	Drug: Ranibizumab and iCo-007 350 mcg; Ranibizumab (0.5 mg) intravitreal injection at baseline followed by iCo-007 (350 μg) intravitreal injection 2 weeks later; re-treatment with ranibizumab (0.5 mg) mandatory at M4 followed by iCo-007 (350 μg) 2 weeks later; Other Names: Group 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VA From Baseline to Month 8	The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 8	Baseline to month 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability	Safety of repeated iCo-007 intravitreal injections in treatment of subjects with Diabetic Macular Edema (DME) as monotherapy and in combination with ranibizumab or laser photocoagulation. Serious consideration will be given if 2 or more patients in a particular treatment arm experience the same drug-related serious adverse event;	Baseline to month 8
Change in VA From Baseline to Month 12	The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 12	Baseline to month 12
Change in Retinal Thickness Measured by OCT From Baseline to Month 8	Group 1	Baseline to month 8
Change in Retinal Thickness Measured	measured by OCT	Baseline to month 12
Duration of iCo-007 Treatment Effect	treatment effect as measured by VA and OCY thickness	Baseline to month 12
Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections	cmax	Baseline to month 12

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Juvenile Diabetes Research Foundation; iCo Therapeutics Inc.
• Investigators: Principal Investigator: Diana V. Do, MD, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center; Principal Investigator: Robert Wong, MD, Austin Retina Associates; Principal Investigator: Michael J. Tolentino, MD, Center for Retina Macula Disease; Principal Investigator: Prema Abraham, MD, Black Hills Regional Eye Institute; Principal Investigator: Eugene Lit, MD, East Bay Retina Institute; Principal Investigator: Michael J. Elman, MD, Elman Retina Group; Principal Investigator: Thomas A. Barnard, MD, Florida Retina Institute; Principal Investigator: Thomas A. Ciulla, MD, Midwest Eye Institute; Principal Investigator: Richard B. Rosen, MD, New York Eye and Ear Infirmary; Principal Investigator: Henry L. Hudson, MD, Retina Centers, P.C.; Principal Investigator: Pravin Dugel, MD, Retina Consultants of Arizona; Principal Investigator: Gregg T. Kokame, MD, Retina Consultants of Hawaii, Pali Momi Medical Center; Principal Investigator: David M. Brown, MD, Retina Consultants Houston; Principal Investigator: Larry S. Halperin, MD, Retina Group of Florida; Principal Investigator: Goergios Papastergio, MD, Retina Institute of Hawaii; Principal Investigator: Ron P. Gallemore, MD. PhD, Retina Macula Institute; Principal Investigator: Brian B. Berger, MD, Retina Research Center; Principal Investigator: Homayoun Tabandeh, MD, Retina Vitreous Associates; Principal Investigator: Dennis M. Marcus, MD, Southeast Retina; Principal Investigator: Robert S. Wirthlin, MD, Spokane Eye Clinic; Principal Investigator: David Callanan, MD, Texas Retina Associates in Arlington; Principal Investigator: Karl G. Csaky, MD, PhD, Texas Retina Associates in Dallas; Principal Investigator: Surendar Purohit, MD, TLC Eye Care & Laser Center; Principal Investigator: Victor H. Gonzalez, MD, Valley Retina Institute; Principal Investigator: Louis Glazer, MD, Vitreo-Retinal Associates; Principal Investigator: Dean Eliott, MD, Massachusetts Eye and Ear Infirmary, Harvard Medical School

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 28, 2012

Study Record Updates

• Last Update Posted (Actual): August 30, 2017
• Last Update Submitted That Met QC Criteria: July 28, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Diabetic Macular Edema (DME)
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: 2010-007-03-DME