A Pharmacokinetic Study: Ranibizumab, Aflibercept and the Effect of Vitrectomy. (VITCLEAR)

To study the effect of pars plana vitrectomy on the intravitreal pharmacokinetics of ranibizumab and to compare the half-life of ranibizumab and aflibercept.

Study Overview

• Status: Completed
• Conditions: Age Related Macular Degeneration
• Intervention / Treatment: Drug: Ranibizumab; Drug: Aflibercept

Detailed Description

This study is a prospective, pharmacokinetic study comparing ranibizumab clearance in two groups of patients; those with and without prior vitrectomy. Additionally it will compare ranibizumab clearance to aflibercept clearance as well as the effect on systemic circulating inflammatory and safety markers. Patients will already be receiving ranibizumab or aflibercept therapy - the injection is itself administered irrespective of their participation in this study and therefore this study will not alter medical management or the choice of therapy.

To estimate ranibizumab and aflibercept clearance, it is important to measure serum concentrations at several intervals within the first 24 hours. Participants will ideally have venous blood sampling at the following times after their ranibizumab or aflibercept injection:

• 1 hour
• 2 hours
• 3 hours
• 4 hours
• 6 hours
• 24 hours
• 2 days
• 4 days
• 1 week*
• 2 weeks
• 4 weeks*

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Adults of either sex aged 55 years and older
• Active neovascular AMD in the study eye
• Intravitreal dose of 0.5 mg ranibizumab or 2 mg aflibercept required, as per current clinical guidelines
• Venous access that is sufficient to allow easy blood sampling on a frequent basis
• Able to give written consent
• Willingness to comply with all study procedures

Exclusion criteria

• Myopia greater than 8 dioptres in the study eye
• Axial length of eye under 20mm or over 26mm
• Aphakia in study eye
• Pseudophakia with a defect in the posterior capsule
• Glaucoma in study eye
• Current renal dialysis
• Presence of inflammatory eye conditions, such as uveitis, or systemic conditions likely to elevate CRP.
• Intraocular surgery within 6 months of enrolment, except for routine phacoemulsification cataract surgery that may occur within 4 months of enrolment
• Current treatment for wet age-related macular degeneration with an intravitreal agent other than ranibizumab or aflibercept in the study eye. Patients expected to change their anti-VEGF agent during the sampling period are also excluded.
• Known significant allergy to ranibizumab or aflibercept
• Participants who, in the opinion of the Investigator, would not be willing or able to comply with the study protocol or provide informed consent.
• Patients with severe anaemia
• Patients who have received anti-VEGF therapy in either eye within 8 weeks of enrolment, or who are likely to require anti-VEGF treatment in the fellow eye during the course of venous sampling. Note that the final venous sample at 4 weeks can be undertaken on the same day as an anti-VEGF injection, but must be taken prior to any injection.
• Patients presently taking any topical (skin or eye), periocular, intraocular, local or systemic treatment with immunosuppressive or anti-inflammatory agents, such as steroids, steroid sparing agents, and NSAIDs. Patients who have received any of these agents within 2 months prior to enrolment are also excluded, as are those thought likely to receive these medications during the course of venous sampling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Ranibizumab (Lucentis); Previous Vitrectomy	Drug: Ranibizumab; Intravitreal injection of ranibizumab; Other Names: Lucentis
Active Comparator: Arm B: Ranibizumab (Lucentis); Non-vitrectomised, PVD / no PVD	Drug: Ranibizumab; Intravitreal injection of ranibizumab; Other Names: Lucentis
Active Comparator: Arm C: Aflibercept (Eylea); Non-vitrectomised, PVD / no PVD	Drug: Aflibercept; Intravitreal injection of aflibercept; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ranibizumab half-life	Vitrectomised and non-vitrectomised patients	12 Months
Aflibercept half-life	Non-vitrectomised patients only	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sub-group analysis of the effect of PVD on ranibizumab half-life	Measurement of half-life (drug assay)	12 months
The effect of ranibizumab and aflibercept concentrations on serum inflammatory and safety marker levels.	Assay levels of cytokines and inflammatory/safety markers	12 months

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Collaborators: King's College London
• Investigators: Principal Investigator: Timothy L Jackson, PhD,FRCOphth, King's College Hospital, London

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 24, 2014
• First Posted (Estimate): June 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab; Aflibercept
• Other Study ID Numbers: EudraCT Number: 2012-005500-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The Investigator(s) shall permit trial-related monitoring, audits, REC review, and regulatory inspections (where appropriate) by providing direct access to source data and other documents (i.e. patients' case sheets, blood test reports, X-ray reports, histology reports etc). Where necessary, inspection may also take place at the site's facilities.