Intravitreal Infliximab for Proliferative Vitreoretinopathy

NCT04891991 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CU272021
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis. Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with the retinal pigment epithelium (RPE) cell contribute to the initiation of PVR. This may occur through the action of TNF-α on the RPE cells inducing changes in cellular morphologies that lead to the formation of fibroblastic cells. Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model. The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment.

Conditions

Rhegmatogenous Retinal Detachment; Proliferative Vitreoretinopathy; Retinal Detachment

Outcome Measures

Primary Outcomes (1)

• Anatomical success

  Anatomical Success will be defined as stable complete retinal reattachment following pars plana vitrectomy and silicone oil removal.

  9 months

Secondary Outcomes (7)

• Visual acuity

  1, 3, 6, and 9 months

• Macular structure

  1, 3, 6, and 9 months

• Macular vascularity

  7 months

• Macular function

  7 months

• Single operation success rate

  9 months

Study Arms (2)

Infliximab group

ACTIVE COMPARATOR

This group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.

Drug: Intravitreal infliximab; Procedure: Pars plana vitrectomy

Standard of care group

SHAM COMPARATOR

This group will undergo standard pars plana vitrectomy.

Procedure: Pars plana vitrectomy

Interventions

Intravitreal infliximab DRUG

1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.

Also known as: Remicade

Infliximab group

Pars plana vitrectomy PROCEDURE

Standard pars plana vitrectomy

Infliximab group; Standard of care group

Eligibility Criteria

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

You may qualify if:

• Age: more than or equal to 18 years
• Primary rhegmatogenous retinal detachment with proliferative vitreoretinopathy more than or equal to grade C

You may not qualify if:

• Patients with a history of open globe injury
• Recurrent retinal detachment or primary failed retinal detachment surgery
• History of vitreoretinal procedure
• Retinal vascular diseases (Diabetic retinopathy, retinal vein occlusion,...etc)
• Pregnant or breastfeeding females
• Inability to attend regular follow-up visits
• History of pulmonary or extra-pulmonary tuberculosis.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, 11956, Egypt

Location

Related Publications (14)

• Nagasaki H, Shinagawa K, Mochizuki M. Risk factors for proliferative vitreoretinopathy. Prog Retin Eye Res. 1998 Jan;17(1):77-98. doi: 10.1016/s1350-9462(97)00007-4.

  PMID: 9537796 BACKGROUND

• Pastor JC. Proliferative vitreoretinopathy: an overview. Surv Ophthalmol. 1998 Jul-Aug;43(1):3-18. doi: 10.1016/s0039-6257(98)00023-x.

  PMID: 9716190 BACKGROUND

• Pastor JC, de la Rua ER, Martin F. Proliferative vitreoretinopathy: risk factors and pathobiology. Prog Retin Eye Res. 2002 Jan;21(1):127-44. doi: 10.1016/s1350-9462(01)00023-4.

  PMID: 11906814 BACKGROUND

• Pennock S, Haddock LJ, Mukai S, Kazlauskas A. Vascular endothelial growth factor acts primarily via platelet-derived growth factor receptor alpha to promote proliferative vitreoretinopathy. Am J Pathol. 2014 Nov;184(11):3052-68. doi: 10.1016/j.ajpath.2014.07.026. Epub 2014 Sep 26.

  PMID: 25261788 BACKGROUND

• Charteris DG, Sethi CS, Lewis GP, Fisher SK. Proliferative vitreoretinopathy-developments in adjunctive treatment and retinal pathology. Eye (Lond). 2002 Jul;16(4):369-74. doi: 10.1038/sj.eye.6700194.

  PMID: 12101443 BACKGROUND

• Leiderman YI, Miller JW. Proliferative vitreoretinopathy: pathobiology and therapeutic targets. Semin Ophthalmol. 2009 Mar-Apr;24(2):62-9. doi: 10.1080/08820530902800082.

  PMID: 19373688 BACKGROUND

• Heimann H, Bartz-Schmidt KU, Bornfeld N, Weiss C, Hilgers RD, Foerster MH; Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment Study Group. Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment: a prospective randomized multicenter clinical study. Ophthalmology. 2007 Dec;114(12):2142-54. doi: 10.1016/j.ophtha.2007.09.013.

  PMID: 18054633 BACKGROUND

• Savur F, Aydemir O, Ilhan N. The effect of infliximab and octreotide on cytokine levels experimental proliferative vitreoretinopathy. Cutan Ocul Toxicol. 2020 Mar;39(1):61-66. doi: 10.1080/15569527.2019.1701000. Epub 2019 Dec 17.

  PMID: 31809602 BACKGROUND

• Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behcet disease: a pilot study in 15 patients. Am J Ophthalmol. 2012 Sep;154(3):534-541.e1. doi: 10.1016/j.ajo.2012.03.035. Epub 2012 Jul 11.

  PMID: 22789563 BACKGROUND

• Pascual-Camps I, Hernandez-Martinez P, Monje-Fernandez L, Dolz-Marco R, Gallego-Pinazo R, Wu L, Arevalo JF, Diaz-Llopis M. Update on intravitreal anti-tumor necrosis factor alpha therapies for ocular disorders. J Ophthalmic Inflamm Infect. 2014 Oct 15;4:26. doi: 10.1186/s12348-014-0026-8. eCollection 2014.

  PMID: 25825604 BACKGROUND

• Pastor JC, Rojas J, Pastor-Idoate S, Di Lauro S, Gonzalez-Buendia L, Delgado-Tirado S. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences. Prog Retin Eye Res. 2016 Mar;51:125-55. doi: 10.1016/j.preteyeres.2015.07.005. Epub 2015 Jul 21.

  PMID: 26209346 BACKGROUND

• Hamza MM, Macky TA, Sidky MK, Ragab G, Soliman MM. INTRAVITREAL INFLIXIMAB IN REFRACTORY UVEITIS IN BEHCET'S DISEASE: A Safety and Efficacy Clinical Study. Retina. 2016 Dec;36(12):2399-2408. doi: 10.1097/IAE.0000000000001109.

  PMID: 27870802 BACKGROUND

• Korthagen NM, van Bilsen K, Swagemakers SM, van de Peppel J, Bastiaans J, van der Spek PJ, van Hagen PM, Dik WA. Retinal pigment epithelial cells display specific transcriptional responses upon TNF-alpha stimulation. Br J Ophthalmol. 2015 May;99(5):700-4. doi: 10.1136/bjophthalmol-2014-306309. Epub 2015 Feb 13.

  PMID: 25680620 BACKGROUND

• Pennock S, Haddock LJ, Eliott D, Mukai S, Kazlauskas A. Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? Prog Retin Eye Res. 2014 May;40:16-34. doi: 10.1016/j.preteyeres.2013.12.006. Epub 2014 Jan 9.

  PMID: 24412519 BACKGROUND

MeSH Terms

Conditions

Vitreoretinopathy, Proliferative; Retinal Detachment

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ayman G Elnahry, MD, PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Hany S Hamza, MD, PhD

  Cairo University

  STUDY CHAIR

• Ahmed M Younes, MD, MSc

  Cairo University

  PRINCIPAL INVESTIGATOR

• Ahmed A Abdel-Kader, MD, PhD

  Cairo University

  STUDY DIRECTOR

• Ahmed M Abdelbaki, MD, PhD

  Cairo University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Ophthalmology

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 19, 2021
• Study Start: November 26, 2021
• Primary Completion: November 10, 2023
• Study Completion: November 10, 2023
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)