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)

• ClinicalTrials.gov Identifier: NCT01565148
• Recruitment Status: Terminated
• First Posted: March 28, 2012
• Results First Posted: August 30, 2017
• Last Update Posted: August 30, 2017
• Sponsor: Johns Hopkins University
• Collaborators: Juvenile Diabetes Research Foundation; iCo Therapeutics Inc.
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

• 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

Condition or disease	Intervention/treatment	Phase
Diabetic Macular Edema	Drug: iCo-007 350 mcg; Drug: iCo-007 700 mcg; Drug: iCo-007 350 mcg and Laser; Drug: Ranibizumab and iCo-007 350 mcg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 185 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 2012
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: Group 4

Outcome Measures

Primary Outcome Measures :

1. Change in VA From Baseline to Month 8 [ Time Frame: 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

Secondary Outcome Measures :

1. Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability [ Time Frame: Baseline to month 8 ]
   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;
2. Change in VA From Baseline to Month 12 [ Time Frame: 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
3. Change in Retinal Thickness Measured by OCT From Baseline to Month 8 [ Time Frame: Baseline to month 8 ]
   Group 1
4. Change in Retinal Thickness Measured [ Time Frame: Baseline to month 12 ]
   measured by OCT
5. Duration of iCo-007 Treatment Effect [ Time Frame: Baseline to month 12 ]
   treatment effect as measured by VA and OCY thickness
6. Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections [ Time Frame: Baseline to month 12 ]
   cmax

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Nebraska

Stanley M Truhlsen Eye Institute

Omaha, Nebraska, United States, 68198-5540

Sponsors and Collaborators

Johns Hopkins University

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

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01565148
• Other Study ID Numbers: 2010-007-03-DME
• First Posted: March 28, 2012
• Results First Posted: August 30, 2017
• Last Update Posted: August 30, 2017
• Last Verified: July 2017

Keywords provided by Johns Hopkins University:

Diabetic Macular Edema (DME)

Additional relevant MeSH terms:

Macular Edema; Edema; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents