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

NCT ID: NCT02174211

Last Updated: 2021-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2020-12-31

Brief Summary

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

Conditions

Age Related Macular Degeneration

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Ranibizumab (Lucentis)

Previous Vitrectomy

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Intravitreal injection of ranibizumab

Arm B: Ranibizumab (Lucentis)

Non-vitrectomised, PVD / no PVD

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Intravitreal injection of ranibizumab

Arm C: Aflibercept (Eylea)

Non-vitrectomised, PVD / no PVD

Group Type: ACTIVE_COMPARATOR

Aflibercept

Intervention Type: DRUG

Intravitreal injection of aflibercept

Interventions

Ranibizumab

Intravitreal injection of ranibizumab

Intervention Type: DRUG

Aflibercept

Intravitreal injection of aflibercept

Intervention Type: DRUG

Other Intervention Names

Lucentis; Eylea

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

King's College London

OTHER

Sponsor Role: collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy L Jackson, PhD,FRCOphth

Role: PRINCIPAL_INVESTIGATOR

King's College Hospital NHS Trust

Locations

King's College Hospital NHS Foundation Trust

London, UK, United Kingdom

Countries

United Kingdom

Other Identifiers

EudraCT Number: 2012-005500-18

Identifier Type: -

Identifier Source: org_study_id