Combined Ranibizumab and Iluvien for Diabetic Macular Oedema

NCT03784443 | Withdrawn Phase 2 DMC

• 1 other identifier: P78912
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This trial investigated whether adding Iluvien sustained release steroid intravitreal eye implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor) intravitreal eye injection treatment for diabetic macular oedema would improve disease stability and reduce the need for regular anti-VEGF intravitreal eye injections over first two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye, is a major cause of poor vision in patients with diabetes. This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital eye clinics in England.

Conditions

Diabetic Macular Edema; Diabetes

Keywords

Diabetes; Eye; Macular Oedema; Intravitreal Injection; Ranibizumab; Fluocinolone Acetonide

Outcome Measures

Primary Outcomes (1)

• Number of Lucentis Injections received in the study eye

  The total number of Lucentis injections needed over 24 months following the intravitreal injection PRN protocol

  24 months

Secondary Outcomes (10)

• Change in visual acuity

  Month 24

• Maintaining at least 20/40 vision

  Month 24

• Proportion of participants with vision loss

  Month 24

• Proportion of participants with visual gain

  Month 24

• Stability of vision

  Over 24 months

Study Arms (2)

Iluvien Arm

ACTIVE COMPARATOR

Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection \[Lucentis\] for first three visits followed by monthly Ranibizumab Injection \[Lucentis\] PRN.

Drug: Iluvien 0.19 MG Drug Implant; Drug: Ranibizumab Injection [Lucentis]

Control Arm

SHAM COMPARATOR

To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection \[Lucentis\] for first three visits followed by monthly Ranibizumab Injection \[Lucentis\] PRN.

Drug: Ranibizumab Injection [Lucentis]; Procedure: Sham Intravitreal Injection

Interventions

Iluvien 0.19 MG Drug Implant DRUG

Fluocinolone Acetonide Sustained Release Intravitreal Implant at Baseline Visit

Also known as: Fluocinolone Acetonide Implant

Iluvien Arm

Ranibizumab Injection [Lucentis] DRUG

Monthly PRN intravitreal injections

Also known as: Lucentis

Control Arm; Iluvien Arm

Sham Intravitreal Injection PROCEDURE

Sham injection without penetrating needle and without drug delivery at baseline visit.

Also known as: Sham Injection with Luer Lock Syringe

Control Arm

Eligibility Criteria

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

You may qualify if:

• General
• Willingness and the ability to provide informed consent.
• Ability and willingness to undertake all scheduled visits, assessment and treatment.
• Age 18 years or above.
• Documented diagnosis of diabetes mellitus (Type I or Type II) as per WHO (World Health Organization) criteria.
• Current regular use of oral anti-hyperglycaemia or insulin therapy.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \<1% per year during the study duration of 24 months.
• Ocular
• Macular thickening due to Diabetic Macular Oedema (DMO) involving the centre of fovea as measured by Spectral Domain OCT with CRT of at least 400 microns.
• DMO confirmed by clinical examination and fundus fluorescein angiography.
• BCVA between 73 to 25 letters inclusive (Snellen equivalent to 6/12 to 6/96) as measured using ETDRS protocol at 4 meters.
• Pseudophakia in the study eye.
• Adequate ocular media clarity and pupillary dilatation allowing for posterior segment examination and OCT scanning.

You may not qualify if:

• General
• Cerebral vascular accident, transient ischaemic attack or myocardial infarction within 3 months prior to day 1 (baseline).
• Pregnancy or breastfeeding, or intention to become pregnant during the study.
• Participation in an investigational trial involving treatment with any drug or devices within 3 months prior to day 1 (baseline) and must not be enrolled in another investigational trial during their participation in this trial.
• Systemic anti-VEGF-base therapies within 3 months prior to day 1 (baseline).
• Ocular
• History of prior intravitreal anti-VEGF therapy or steroid implant in the study eye.
• History of proliferative diabetic retinopathy.
• History of rubeosis or current rubeosis.
• History of neovascularization, tractional retinal detachment, retinal vein occlusion, or significant pre-retinal fibrosis distorting the macular architecture.
• History of retinal detachment or macular hole stage 3 or above.
• History of vitreoretinal surgery.
• Aphakia.
• History of glaucoma or uncontrolled ocular hypertension.
• Active or suspected ocular or periocular infection or inflammation, including viral diseases of the cornea, conjunctiva and retina, such as active epithelial herpes simplex keratitis (dendritic keratitis), varicella, mycobacterial infections, and fungal diseases.

Sponsors & Collaborators

• Imperial College London: lead

Related Publications (21)

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• Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012 Mar;35(3):556-64. doi: 10.2337/dc11-1909. Epub 2012 Feb 1.

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• Virgili G, Parravano M, Menchini F, Evans JR. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev. 2014 Oct 24;(10):CD007419. doi: 10.1002/14651858.CD007419.pub4.

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• Grover D, Li TJ, Chong CC. Intravitreal steroids for macular edema in diabetes. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005656. doi: 10.1002/14651858.CD005656.pub2.

  PMID: 18254088 BACKGROUND

• Goni FJ, Stalmans I, Denis P, Nordmann JP, Taylor S, Diestelhorst M, Figueiredo AR, Garway-Heath DF. Elevated Intraocular Pressure After Intravitreal Steroid Injection in Diabetic Macular Edema: Monitoring and Management. Ophthalmol Ther. 2016 Jun;5(1):47-61. doi: 10.1007/s40123-016-0052-8. Epub 2016 May 10.

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• Parrish RK 2nd, Campochiaro PA, Pearson PA, Green K, Traverso CE; FAME Study Group. Characterization of Intraocular Pressure Increases and Management Strategies Following Treatment With Fluocinolone Acetonide Intravitreal Implants in the FAME Trials. Ophthalmic Surg Lasers Imaging Retina. 2016 May 1;47(5):426-35. doi: 10.3928/23258160-20160419-05.

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• Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003 Sep;110(9):1690-6. doi: 10.1016/S0161-6420(03)00568-2.

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• Funatsu H, Yamashita H, Sakata K, Noma H, Mimura T, Suzuki M, Eguchi S, Hori S. Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema. Ophthalmology. 2005 May;112(5):806-16. doi: 10.1016/j.ophtha.2004.11.045.

  PMID: 15878060 BACKGROUND

• Aiello LP. Angiogenic pathways in diabetic retinopathy. N Engl J Med. 2005 Aug 25;353(8):839-41. doi: 10.1056/NEJMe058142. No abstract available.

  PMID: 16120866 BACKGROUND

• Wang K, Wang Y, Gao L, Li X, Li M, Guo J. Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008 Aug;31(8):1541-6. doi: 10.1248/bpb.31.1541.

  PMID: 18670086 BACKGROUND

• Minassian DC, Owens DR, Reidy A. Prevalence of diabetic macular oedema and related health and social care resource use in England. Br J Ophthalmol. 2012 Mar;96(3):345-9. doi: 10.1136/bjo.2011.204040. Epub 2011 May 20.

  PMID: 21602478 BACKGROUND

• Arevalo JF, Lasave AF, Wu L, Acon D, Farah ME, Gallego-Pinazo R, Alezzandrini AA, Fortuna V, Quiroz-Mercado H, Salcedo-Villanueva G, Maia M, Serrano M, Rojas S; Pan-American Collaborative Retina Study Group (PACORES). Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan-American Collaborative Retina Study group. Br J Ophthalmol. 2016 Dec;100(12):1605-1610. doi: 10.1136/bjophthalmol-2015-307950. Epub 2016 Feb 24.

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• Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, Brucker AJ, Ferris FL, Hampton GR, Jhaveri C, Melia M, Beck RW; Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. Epub 2016 Feb 27.

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• Mehta H, Gillies M, Fraser-Bell S. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema. Ther Adv Chronic Dis. 2015 Sep;6(5):234-45. doi: 10.1177/2040622315590319.

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• Hernandez-Bel L, Cervera-Taulet E, Navarro-Palop C, Castro-Navarro V, Chiarri-Toumit C, Montero-Hernandez J. Sequential Dexamethasone and Aflibercept Treatment in Patients with Diabetic Macular Edema: Structural and Functional Outcomes at 52 Weeks. Ophthalmologica. 2019;241(2):98-104. doi: 10.1159/000489345. Epub 2018 Jul 11.

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• Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, Garretson B, Gupta A, Hariprasad SM, Bailey C, Reichel E, Soubrane G, Kapik B, Billman K, Kane FE, Green K; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012 Oct;119(10):2125-32. doi: 10.1016/j.ophtha.2012.04.030. Epub 2012 Jun 21.

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MeSH Terms

Conditions

Diabetes Mellitus; Macular Edema

Interventions

Fluocinolone Acetonide; Drug Implants; Ranibizumab; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Richard Cheong-Leen

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug. The Iluvien and the sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double masking randomized control trial with 2 parallel treatment arms: intervention (Iluvien plus Ranibizumab) vs control (Sham plus Ranibizumab)

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: September 1, 2019
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2023
• Last Updated: October 2, 2023

Record last verified: 2023-09