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A Pharmacokinetic stuDy of intRavitreal Aflibercept Injection in Vitrectomized and Non-vitrectomized Eyes With Diabetic Macular Edema (DRAW-2)

Primary Purpose

Diabetic Macular Edema

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Intravitreal Aflibercept

About this trial

This is an interventional treatment trial for Diabetic Macular Edema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A patient must meet the following criteria to be eligible for inclusion in the study:
- Age > 18 years with diabetes
- Diabetic macular edema (DME) with
30 patients with non-vitrectomized eyes
30 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

Exclusion Criteria:

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.

Sites / Locations

Byers Eye Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Vitrectomized Eyes

Non-Vitrectomized Eyes

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Plasma aflibercept levels

• Investigate and characterize plasma concentrations (free and bound) following injections of intravitreal aflibercept in vitrectomized and non-vitrectomized eyes with diabetic macular edema

Correlation of drug concentration with ophthalmic outcomes

Correlate with changes in ocular concentration of drug change in BCVA change in CRT change in DRSS changes observed on OCT-A number of injections

Safety Outcomes

Compare adverse events during the trial to the expected adverse events on the Aflibercept label to assess ocular and systemic safety of intravitreal aflibercept.

Full Information

NCT ID

NCT04588948

First Posted

September 29, 2020

Last Updated

April 21, 2022

Sponsor

Stanford University

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04588948

Brief Title

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

Acronym

DRAW-2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Study did not proceed due to funding issues.

Study Start Date

December 2020 (Anticipated)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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

Detailed Description

Little information is known about the intraocular pharmacokinetics of intravitreal aflibercept injection in human eyes of Diabetic macular edema (DME) patients. In addition, the durability of intravitreal aflibercept injection in vitrectomized eyes is not known, since individuals with a history of vitrectomy have been excluded from clinical trials in DME. Although we recently conducted a prospective study (the DRAW study) to evaluate the intraocular pharmacokinetics of IAI in eyes with neovascular age-related macular degeneration (AMD), this research did not include eyes with DME. There has been a paucity of studies on systemic levels of free aflibercept following intravitreal aflibercept injection in DME patients, which would have implications for normal vascular hemostasis and wound repair in which vascular endothelial growth factor (VEGF) plays an important role. The proposed research will fill in these gaps in the knowledge base for intravitreal aflibercept injection. 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. 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. Study eyes will receive intravitreal aflibercept at baseline and then starting at month 2 there will be no mandatory injection. Subject will receive additional aflibercept on an as needed basis (PRN) if DME is still present. AC fluid and blood draw will be performed prior to first PRN dose of intravitreal aflibercept. Study will involve following procedures: bio-microscopy, dilated fundoscopic exam, measurement of intraocular pressure, measurement of best corrected visual acuity (BCVA), fundus photograph, optical coherence tomography (OCT) and OCT-Angiography (OCT-A). Patients will be followed monthly for 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Macular Edema

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vitrectomized Eyes

Arm Type

Experimental

Arm Description

Arm Title

Non-Vitrectomized Eyes

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Intravitreal Aflibercept

Other Intervention Name(s)

Eylea

Intervention Description

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

Primary Outcome Measure Information:

Title

Intravitreal Aflibercept Pharmacokinetics

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Plasma aflibercept levels

Description

• Investigate and characterize plasma concentrations (free and bound) following injections of intravitreal aflibercept in vitrectomized and non-vitrectomized eyes with diabetic macular edema

Time Frame

12 months

Title

Correlation of drug concentration with ophthalmic outcomes

Description

Correlate with changes in ocular concentration of drug change in BCVA change in CRT change in DRSS changes observed on OCT-A number of injections

Time Frame

over 12 months

Title

Safety Outcomes

Description

Compare adverse events during the trial to the expected adverse events on the Aflibercept label to assess ocular and systemic safety of intravitreal aflibercept.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A patient must meet the following criteria to be eligible for inclusion in the study: Age > 18 years with diabetes Diabetic macular edema (DME) with 30 patients with non-vitrectomized eyes 30 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Brown, MD

Organizational Affiliation

Retina Consultants Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

Byers Eye Institute

City

Palo Alto

State/Province

California

ZIP/Postal Code

94303

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26903722

Citation

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.

Results Reference

background

PubMed Identifier

23990705

Citation

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.

Results Reference

background

PubMed Identifier

31370346

Citation

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.

Results Reference

background

PubMed Identifier

22836776

Citation

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.

Results Reference

background

PubMed Identifier

25737148

Citation

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.

Results Reference

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Learn more about this trial

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

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