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

Age Related Macular Degeneration Clinical Trial

— VITCLEAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02174211
• Other study ID #: EudraCT Number: 2012-005500-18
• Status: Completed
• Phase: N/A
• Start date: June 2014
• Est. completion date: December 2020

Study information

• Verified date: April 2021
• Source: King's College Hospital NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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*

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: December 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Age Related Macular Degeneration
• Macular Degeneration

Intervention

Drug:
• Ranibizumab
Intravitreal injection of ranibizumab
• Aflibercept
Intravitreal injection of aflibercept

Locations

Country	Name	City	State
United Kingdom	King's College Hospital NHS Foundation Trust	London	UK

Sponsors (2)

Lead Sponsor	Collaborator
King's College Hospital NHS Trust	King's College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ranibizumab half-life	Vitrectomised and non-vitrectomised patients	12 Months
Primary	Aflibercept half-life	Non-vitrectomised patients only	12 Months
Secondary	Sub-group analysis of the effect of PVD on ranibizumab half-life	Measurement of half-life (drug assay)	12 months
Secondary	The effect of ranibizumab and aflibercept concentrations on serum inflammatory and safety marker levels.	Assay levels of cytokines and inflammatory/safety markers	12 months