Back to resultsA Pharmacokinetic Study: Ranibizumab, Aflibercept and the Effect of Vitrectomy. (VITCLEAR)
Primary Purpose
Age Related Macular Degeneration
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Ranibizumab
Aflibercept
Sponsored by
About this trial
This is an interventional treatment trial for Age Related Macular Degeneration
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.
Sites / Locations
- King's College Hospital NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Arm A: Ranibizumab (Lucentis)
Arm B: Ranibizumab (Lucentis)
Arm C: Aflibercept (Eylea)
Arm Description
Previous Vitrectomy
Non-vitrectomised, PVD / no PVD
Non-vitrectomised, PVD / no PVD
Outcomes
Primary Outcome Measures
Ranibizumab half-life
Vitrectomised and non-vitrectomised patients
Aflibercept half-life
Non-vitrectomised patients only
Secondary Outcome Measures
Sub-group analysis of the effect of PVD on ranibizumab half-life
Measurement of half-life (drug assay)
The effect of ranibizumab and aflibercept concentrations on serum inflammatory and safety marker levels.
Assay levels of cytokines and inflammatory/safety markers
Full Information
NCT ID
NCT02174211
First Posted
June 24, 2014
Last Updated
April 29, 2021
Sponsor
King's College Hospital NHS Trust
Collaborators
King's College London
1. Study Identification
Unique Protocol Identification Number
NCT02174211
Brief Title
A Pharmacokinetic Study: Ranibizumab, Aflibercept and the Effect of Vitrectomy.
Acronym
VITCLEAR
Official Title
A Pharmacokinetic Study: Ranibizumab, Aflibercept and the Effect of Vitrectomy.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
November 2020 (Actual)
Study Completion Date
December 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King's College Hospital NHS Trust
Collaborators
King's College London
4. Oversight
Data Monitoring Committee
No
5. Study Description
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*
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Age Related Macular Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
59 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Ranibizumab (Lucentis)
Arm Type
Active Comparator
Arm Description
Previous Vitrectomy
Arm Title
Arm B: Ranibizumab (Lucentis)
Arm Type
Active Comparator
Arm Description
Non-vitrectomised, PVD / no PVD
Arm Title
Arm C: Aflibercept (Eylea)
Arm Type
Active Comparator
Arm Description
Non-vitrectomised, PVD / no PVD
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Intravitreal injection of ranibizumab
Intervention Type
Drug
Intervention Name(s)
Aflibercept
Other Intervention Name(s)
Eylea
Intervention Description
Intravitreal injection of aflibercept
Primary Outcome Measure Information:
Title
Ranibizumab half-life
Description
Vitrectomised and non-vitrectomised patients
Time Frame
12 Months
Title
Aflibercept half-life
Description
Non-vitrectomised patients only
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Sub-group analysis of the effect of PVD on ranibizumab half-life
Description
Measurement of half-life (drug assay)
Time Frame
12 months
Title
The effect of ranibizumab and aflibercept concentrations on serum inflammatory and safety marker levels.
Description
Assay levels of cytokines and inflammatory/safety markers
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy L Jackson, PhD,FRCOphth
Organizational Affiliation
King's College Hospital, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
King's College Hospital NHS Foundation Trust
City
London
State/Province
UK
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing 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.
Learn more about this trial
A Pharmacokinetic Study: Ranibizumab, Aflibercept and the Effect of Vitrectomy.
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