A Pharmacokinetic stuDy of intRavitreal Aflibercept Injection in Vitrectomized and Non-vitrectomized Eyes With Diabetic Macular Edema

NCT04588948 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 58689VGFTe-DME-2041
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to investigate and characterize the intraocular pharmacokinetics (free and bound) following intravitreal aflibercept injection (IAI) in vitrectomized and non-vitrectomized eyes with diabetic macular edema The secondary objectives are to -

• Investigate and characterize plasma concentrations (free and bound) following injections of intravitreal aflibercept in vitrectomized and non-vitrectomized eyes with diabetic macular edema
• Correlate with changes in ocular concentration of drug over 12 months -
• change in Best Corrected Visual Acuity (BCVA)
• change in Central Retinal Thickness (CRT)
• change in Diabetic Retinopathy Severity Scale (DRSS)
• changes observed on Ocular coherence tomography angiography (OCT-A)
• number of injections
• Evaluate ocular and systemic safety of intravitreal aflibercept
• Additional plasma and anterior chamber (AC) fluid cytokine analysis will be performed if sufficient samples are available

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (1)

• Intravitreal Aflibercept Pharmacokinetics

  Intraocular aflibercept levels (free and bound) after intravitreal aflibercept injection.The primary objective is to investigate and characterize the intraocular pharmacokinetics (free and bound) following intravitreal aflibercept injection (IAI) in vitrectomized and non-vitrectomized eyes with diabetic macular edema

  12 months

Secondary Outcomes (3)

• Plasma aflibercept levels

  12 months

• Correlation of drug concentration with ophthalmic outcomes

  over 12 months

• Safety Outcomes

  12 months

Study Arms (2)

Vitrectomized Eyes

EXPERIMENTAL

The study is an exploratory investigation to evaluate the intraocular and systemic pharmacokinetics of intravitreal aflibercept. A sample size of 60 eyes was chosen to provide a sample of 30 non-vitrectomized eyes and 30 vitrectomized eyes to evaluate.

Drug: Intravitreal Aflibercept

Non-Vitrectomized Eyes

EXPERIMENTAL

The study is an exploratory investigation to evaluate the intraocular and systemic pharmacokinetics of intravitreal aflibercept. A sample size of 60 eyes was chosen to provide a sample of 30 non-vitrectomized eyes and 30 vitrectomized eyes to evaluate.

Drug: Intravitreal Aflibercept

Interventions

Intravitreal Aflibercept DRUG

Two arms (non-vitrectomized, and vitrectomized) are included in the study to evaluate the effect of vitrectomy on the intraocular and systemic pharmacokinetics of intravitreal aflibercept injection

Also known as: Eylea

Non-Vitrectomized Eyes; Vitrectomized Eyes

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years with diabetes
• Diabetic macular edema (DME) with
• patients with non-vitrectomized eyes
• patients with vitrectomized eyes
• Prior DME treatment allowed if
• Intravitreal anti-VEGF agent 6 months before study day 0
• Intravitreal steroid administered 5 months before study day 0
• Laser photocoagulation administered 4 months before study day 0
• Phakic and pseudophakic eyes are allowed in the study.
• Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Willing and able to comply with clinic visits and study-related procedures

You may not qualify if:

• A patient who meets any of the following criteria will be excluded from the study:
• Presence of other retinal vascular diseases (AMD, vein occlusion) that could affect the VEGF levels within the eye
• History of fluocinolone acetonide intravitreal implant
• Known hypersensitivity to aflibercept
• Autoimmune disease of the anterior segment or posterior chamber including chronic keratoconjunctivitis sicca, uveitis, iritis/scleritis, blepharitis of either eye
• Infectious conjunctivitis, keratitis, or endophthalmitis of either eye
• Previous participation in any studies of investigational drugs within 1 month preceding Day 0
• Any clinically significant acute or chronic medical condition that would preclude participation in a clinical study
• Pregnant or breastfeeding women
• Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception prior to the initial dose/start of the first treatment, during the study, and for at least 3 months after the last dose. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly.
• Contraception is not required for men with documented vasectomy. \*\*Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Sponsors & Collaborators

• Stanford University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Byers Eye Institute

Palo Alto, California, 94303, United States

Location

Related Publications (5)

• Al-Hinai AS. Experience of intravitreal injections in a tertiary Hospital in Oman. Oman J Ophthalmol. 2015 Sep-Dec;8(3):166-70. doi: 10.4103/0974-620X.169896.

  PMID: 26903722 BACKGROUND

• Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C. Aflibercept in wet AMD: specific role and optimal use. Drug Des Devel Ther. 2013 Aug 5;7:711-22. doi: 10.2147/DDDT.S40215. eCollection 2013.

  PMID: 23990705 BACKGROUND

• Garcia-Quintanilla L, Luaces-Rodriguez A, Gil-Martinez M, Mondelo-Garcia C, Maronas O, Mangas-Sanjuan V, Gonzalez-Barcia M, Zarra-Ferro I, Aguiar P, Otero-Espinar FJ, Fernandez-Ferreiro A. Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration. Pharmaceutics. 2019 Jul 31;11(8):365. doi: 10.3390/pharmaceutics11080365.

  PMID: 31370346 BACKGROUND

• Kakinoki M, Sawada O, Sawada T, Saishin Y, Kawamura H, Ohji M. Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys. Invest Ophthalmol Vis Sci. 2012 Aug 24;53(9):5877-80. doi: 10.1167/iovs.12-10164.

  PMID: 22836776 BACKGROUND

• Ahn SJ, Ahn J, Park S, Kim H, Hwang DJ, Park JH, Park JY, Chung JY, Park KH, Woo SJ. Erratum. Intraocular Pharmacokinetics of Ranibizumab in Vitrectomized Versus Nonvitrectomized Eyes. Invest Ophthalmol Vis Sci. 2015 Mar 3;56(3):1473-4. doi: 10.1167/iovs.13-13054a. No abstract available.

  PMID: 25737148 BACKGROUND

MeSH Terms

Interventions

aflibercept

Study Officials

• David Brown, MD

  Retina Consultants Houston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The study is an exploratory investigation to evaluate the intraocular and systemic pharmacokinetics of intravitreal aflibercept. A sample size of 60 eyes was chosen to provide a sample of 30 non-vitrectomized eyes and 30 vitrectomized eyes to evaluate. This sample size will allow for an initial determination of the pharmacokinetics of intravitreal aflibercept injection inside the eye and in the systemic circulation of eyes with DME.One eye per patient may be eligible. In this research proposal, participants will be followed for 12-month period and have 17 study visits

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 19, 2020
• Study Start: December 1, 2020
• Primary Completion: June 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)